The blood-brain barrier (BBB) serves as a highly selective interface that regulates the transport of molecules between the blood and the brain. Its integrity is essential for maintaining neuronal homeostasis and preventing neuroinflammation. Hyperglycemia, a hallmark of diabetes, is linked to cognitive deficits and central nervous system (CNS) pathologies, including vascular dementia, stroke, and Alzheimer's disease, with BBB damage as a potential contributing factor. As the global prevalence of diabetes rises, understanding the connection between hyperglycemia and BBB dysfunction may facilitate the development of novel treatments that protect or restore BBB integrity, thereby alleviating the neurological complications of diabetes. Furthermore, it may aid in the development of targeted therapies for diabetes-related neurological complications. This literature review examines the emerging insights into the relationship between hyperglycemia and BBB dysfunction. It focuses on the mechanisms underlying BBB dysfunction, the clinical manifestations of this dysfunction in diabetes and cerebrovascular diseases, and potential therapeutic interventions.

Understanding the complex workings of the brain is one of the most significant challenges in neuroscience, providing insights into normal brain function, neurological diseases, and the effects of potential therapeutics. A major challenge in this field lies in the limitations of traditional brain imaging techniques, which often capture only fragments of the complex puzzle of brain function. Our research employs a novel approach termed 'molecular connectivity' (MC), which combines the strengths of various imaging methods to provide a comprehensive view of how specific molecules, such as the serotonin transporter, interact across different brain regions and influence brain function. This innovative technique bridges the gap between functional magnetic resonance imaging (fMRI), known for its ability to monitor brain activity by tracking blood flow, and positron emission tomography (PET), which visualizes specific molecular changes. By integrating these methods, we can better understand how drugs influence brain function. Our study focuses on the application of dynamic [11C]DASB PET scans to map the distribution of serotonin transporters, key players in regulating mood and emotions, and examines how these transporters are altered following exposure to methylenedioxymethamphetamine (MDMA), which is commonly known as ecstasy. Through a detailed comparison of MC with traditional measures of brain connectivity, we reveal significant patterns that closely align with physiological changes. Our results revealed clear changes in molecular connectivity after a single dose of MDMA, establishing a direct link between the effects of drugs on serotonin transporter occupancy and changes in the functional brain network. This work offers a novel methodology for the in-depth study of brain function at the molecular level and opens new pathways for understanding how drugs modulate brain activity.

Given mounting literature linking environmental adversity with neurobiological alterations, other evidence has shown association between excess adiposity and attenuated brain development, leading to our current question of how the developing brain interacts with change in body composition in response to environmental challenges. Using data from the Adolescent Brain Cognitive Development (ABCD®) Study, we conducted mediation analyses and demonstrated that socioeconomic deprivation (SED) was associated with lower total brain and cortical volumes via the mediation of higher waist-to-height ratio (WHtR), and that WHtR likewise mediated the association of SED with global brain structures. The prefrontal structures showed region- and direction-specific pathways, with bilateral superior and middle frontal gyrus being most consistently related with WHtR in addition to the impact of SED. These findings reveal a functional trade-off between brain development and fat deposition in response to environmental deprivation, and may have implications for understanding neurocognitive and somatic development among children and adolescents in different socioeconomic contexts.

Neurodevelopment is a multifaceted and tightly regulated process essential for the formation, maturation, and functional specialization of the nervous system. It spans critical stages, including cellular proliferation, differentiation, migration, synaptogenesis, and synaptic pruning, which collectively establish the foundation for cognitive, behavioral, and emotional functions. Metabolism serves as a cornerstone for neurodevelopment, providing the energy and substrates necessary for biosynthesis, signaling, and cellular activities.

Key metabolic pathways, including glycolysis, lipid metabolism, and amino acid metabolism, support processes such as cell proliferation, myelination, and neurotransmitter synthesis. Crucial signaling pathways, such as insulin, mTOR, and AMPK, further regulate neuronal growth, synaptic plasticity, and energy homeostasis. Dysregulation of these metabolic processes is linked to a spectrum of neurodevelopmental disorders, including autism spectrum disorders (ASDs), intellectual disabilities, and epilepsy.

This review investigates the intricate interplay between metabolic processes and neurodevelopment, elucidating the molecular mechanisms that govern brain development and the pathogenesis of neurodevelopmental disorders. Additionally, it highlights potential avenues for the development of innovative strategies aimed at enhancing brain health and function.

Assessment of recovery from mild traumatic brain injury (mTBI) is complex and challenging. Post-exertion testing, where individuals undergo objective testing following physical exercise, has shown promise in identifying mTBI-related impairments that may not be evident at rest, but could hinder a safe return to sport.

To conduct a systematic review to determine if physical exertion affects objective physiological or sensorimotor tests differently in individuals with mTBI compared with healthy controls.

A systematic search of 11 databases and five trial registries on 30 May 2024 identified reports that: (i) compared individuals aged 12-65 years within 12 months of mTBI against healthy control participants, (ii) investigated the effects of a single session of physical exertion and (iii) collected before, during or after exertion, objective measures of physiological or sensorimotor function. Risk of bias was assessed with the Risk Of Bias In Non-randomized Studies of Interventions tool. Results were analysed descriptively.

The review included 22 studies with 536 participants wih mTBI. Risk of bias was deemed high. At rest, 8/22 (36%) studies detected differences in physiological responses between participants wih mTBI and healthy control participants. During or after exertion, 21/22 (96%) studies detected differences in physiological responses, including cardiovascular, respiratory and cerebral autoregulation.

The findings indicate that objective testing during or after physical exertion can enhance the ability to detect mTBI-related impairments in various physiological parameters, and this concept could be considered when monitoring recovery and return to sport. Further studies are needed.

CRD42023411681.

Despite decades of research in brain energy metabolism and to what extent different cell types utilize distinct substrates for their energy metabolism, this topic remains a vibrant area of neuroscience research. In this review, we focus on the substrates utilized by the inhibitory GABAergic neurons, which has been less explored than glutamatergic neurons. First, we discuss how GABAergic neurons may utilize both glucose, lactate, or ketone bodies under different functional conditions, and provide some preliminary data suggesting that unlike glutamatergic neurons, GABAergic neurons work well when substrate supply is restricted to lactate. We end by discussing the role of GABAergic neuron energy metabolism in pathologies where failure of inhibitory function play a central role, namely epilepsy, hepatic encephalopathy, and Alzheimer's disease.

Ageing is often accompanied by cognitive decline and an increased risk of dementia. Exercise is a powerful tool for slowing brain ageing and enhancing cognitive function, as well as alleviating depression, improving sleep, and promoting overall well-being. The connection between exercise and healthy brain ageing is particularly intriguing, with exercise-induced pathways playing key roles. This review explores the link between exercise and brain health, focusing on how skeletal muscle influences the brain through muscle-brain crosstalk. We examine the interaction between the brain with well-known myokines, including brain-derived neurotrophic factor, macrophage colony-stimulating factor, vascular endothelial growth factor and cathepsin B. Neuroinflammation accumulates in the ageing brain and leads to cognitive decline, impaired motor skills and increased susceptibility to neurodegenerative diseases. Finally, we examine the evidence on the effects of exercise on neuronal myelination in the central nervous system, a crucial factor in maintaining brain health throughout the lifespan.

DNA damage is a common event in cells, resulting from both internal and external factors. The maintenance of genomic integrity is vital for cellular function and physiological processes. The inadequate repair of DNA damage results in the genomic instability, which has been associated with the development and progression of various human diseases. Accumulation of DNA damage can lead to multiple diseases, such as neurodegenerative disorders, cancers, immune deficiencies, infertility, and ageing. This comprehensive review delves the impact of alterations in DNA damage response genes (DDR) and tries to elucidate how and to what extent the same traits modulate diverse major human diseases, such as cancer, neurodegenerative diseases, and immunological disorders. DDR is apparently the trait connecting important complex disorders in humans. However, the pathogenesis of the above disorders and diseases are different and lead to divergent consequences. It is important to discover the switch(es) that direct further the pathogenic process either to proliferative, or degenerative diseases. Our understanding of the influence of DNA damage on diverse human disorders may enable the development of the strategies to prevent, diagnose, and treat these diseases. In our article, we analysed publicly available GWAS summary statistics from the NHGRI-EBI GWAS Catalog and identified 12 009 single-nucleotide polymorphisms (SNPs) associated with cancer. Among these, 119 SNPs were found in DDR pathways, exhibiting significant P-values. Additionally, we identified 44 SNPs linked to various cancer types and neurodegenerative diseases (NDDs), including four located in DDR-related genes: ATM, CUX2, and WNT3. Furthermore, 402 SNPs were associated with both cancer and immunological disorders, with two found in the DDR gene RAD51B. This highlights the versatility of the DDR pathway in multifactorial diseases. However, the specific mechanisms that regulate DDR to initiate distinct pathogenic processes remain to be elucidated.

The human brain is a complex system with high metabolic demands and extensive connectivity that requires control to balance energy consumption and functional efficiency over time. How this control is manifested on a whole-brain scale is largely unexplored, particularly what the associated costs are. Using the network control theory, here, we introduce a novel concept, time-averaged control energy (TCE), to quantify the cost of controlling human brain dynamics at rest, as measured from functional and diffusion MRI. Importantly, TCE spatially correlates with oxygen metabolism measures from the positron emission tomography, providing insight into the bioenergetic footing of resting-state control. Examining the temporal dimension of control costs, we find that brain state transitions along a hierarchical axis from sensory to association areas are more efficient in terms of control costs and more frequent within hierarchical groups than between. This inverse correlation between temporal control costs and state visits suggests a mechanism for maintaining functional diversity while minimizing energy expenditure. By unpacking the temporal dimension of control costs, we contribute to the neuroscientific understanding of how the brain governs its functionality while managing energy expenses.

Neural oscillations facilitate the functioning of the human brain in spatial and temporal dimensions at various frequencies. These oscillations feature a universal frequency architecture that is governed by brain anatomy, ensuring frequency specificity remains invariant across different measurement techniques. Initial magnetic resonance imaging (MRI) methodology constrained functional MRI (fMRI) investigations to a singular frequency range, thereby neglecting the frequency characteristics inherent in blood oxygen level-dependent oscillations. With advancements in MRI technology, it has become feasible to decode intricate brain activities via multi-band frequency analysis (MBFA). During the past decade, the utilization of MBFA in fMRI studies has surged, unveiling frequency-dependent characteristics of spontaneous slow oscillations (SSOs) believed to base dark energy in the brain. There remains a dearth of conclusive insights and hypotheses pertaining to the properties and functionalities of SSOs in distinct bands. We surveyed the SSO MBFA studies during the past 15 years to delineate the attributes of SSOs and enlighten their correlated functions. We further proposed a model to elucidate the hierarchical organization of multi-band SSOs by integrating their function, aimed at bridging theoretical gaps and guiding future MBFA research endeavors.

Cocaine use is a rising global concern, and increased use is accompanied by a significant increase in people entering treatment for the first time. However, there are still no complete therapies, and preclinical tools are necessary to both understand the action of cocaine and mitigate for its effects. Cocaine exposure rapidly impacts cellular and mitochondrial health, leading to oxidative stress. This study evaluated the effects of acute, repeated, and chronic cocaine exposure on C17.2 neural precursor cells. A single exposure to high concentrations of cocaine caused rapid cell death, with lower concentrations increasing markers of oxidative stress and mitochondrial dysfunction within 4 h of exposure. Alterations in cellular bioenergetics and mitochondrial fusion and fission gene expression (OPA1, DRP1) were also observed, which returned to baseline by 24 h after insult. Repeated exposure over 3 days reduced cell proliferation and spare mitochondrial respiratory capacity, suggesting compromised cellular resilience. Interestingly, chronic exposure over 4 weeks led to cellular adaptation and restoring mitochondrial bioenergetics and ATP production while mitigating for oxidative stress. These findings highlight the time-dependent cellular effects of cocaine, with initial toxicity and mitochondrial impairment transitioning to adaptive responses under chronic exposure.

Two common mechanisms contributing to multiple neurological disorders, including Alzheimer's disease, are brain glucose hypometabolism (BGHM) and brain iron accumulation (BIA). Currently, BGHM and BIA are both widely acknowledged as biomarkers that aid in diagnosing CNS disorders, distinguishing between disorders with similar symptoms, and tracking disease progression. Therapeutics targeting BGHM and BIA in Alzheimer's disease can be beneficial in treating neurocognitive symptoms. This review addresses the evidence for the therapeutic potential of targeting BGHM and BIA in multiple CNS disorders. Intranasal insulin, which is anti-inflammatory and increases brain cell energy, and intranasal deferoxamine, which reduces oxidative damage and inflammation, represent promising treatments targeting these mechanisms. Both BGHM and BIA are promising therapeutic targets for AD and other CNS disorders.

A long-standing debate in neuroscience concerns whether individual neurons are organized into functionally distinct populations that encode information differently ("categorical" representations [1-3]) and the implications for neural computation. Here, we systematically analyzed how cortical neurons encode cognitive, sensory, and movement variables across 43 cortical regions during a complex task (14,000+ units from the International Brain Laboratory public Brain-wide Map data set [4]) and studied how these properties change across the sensory-cognitive cortical hierarchy [5]. We found that the structure of the neural code was scale-dependent: on a whole-cortex scale, neural selectivity was categorical and organized across regions in a way that reflected their anatomical connectivity. However, within individual regions, categorical representations were rare and limited to primary sensory areas. Remarkably, the degree of categorical clustering of neural selectivity was inversely correlated to the dimensionality of neural representations, suggesting a link between single-neuron selectivity and computational properties of population codes that we explained in a mathematical model. Finally, we found that the fraction of linearly separable combinations of experimental conditions ("Shattering Dimensionality" [6]) was near maximal across all areas, indicating a robust and uniform ability for flexible information encoding throughout the cortex. In conclusion, our results provide systematic evidence for a non-categorical, high-dimensional neural code in all but the lower levels of the cortical hierarchy.

In neurons, the quantities of mRNAs and proteins are traditionally assumed to be determined by functional, electrical or genetic factors. Yet, there may also be global, currently unknown computational rules that are valid across different molecular species inside a cell. Surprisingly, our results show that the energy for molecular turnover is a significant cellular expense, en par with spiking cost, and which requires energy-saving strategies. We show that the drive to save energy determines transcript quantities and their location while acting differently on each molecular species depending on the length, longevity and other features of the respective molecule. We combined our own data and experimental reports from five other large-scale mRNA and proteomics screens, comprising more than ten thousand molecular species to reveal the underlying computational principles of molecular localisation. We found that energy minimisation principles explain experimentally-reported exponential rank distributions of mRNA and protein copy numbers. Our results further reveal robust energy benefits when certain mRNA classes are moved into dendrites, for example mRNAs of proteins with long amino acid chains or mRNAs with large non-coding regions and long half-lives proving surprising insights at the level of molecular populations.

The purpose of this study was to advance our understanding of the neurobiology of healthy aging, which is crucial for improving quality of life and preventing age-related diseases. Despite its importance, a comprehensive investigation of this process has yet to be fully characterized.

We used a hybrid PET/MRI scanner to assess neurophysiological parameters in 80 healthy individuals aged 20-78. Cerebral amyloid-beta (Aβ) deposition and glucose metabolism were assessed using PET scans, while participants underwent simultaneous MRI scans.

We found a positive correlation between Aβ-deposition and aging, and a negative correlation between glucose metabolism and aging. The insula showed the strongest negative correlation between glucose metabolism and age (Spearman's r = -0.683, 95% CI [-0.79, -0.54], p < 0.0001), while the posterior cingulate cortex had the strongest positive correlation between Aβ-deposition and age (Spearman's r = 0.479, 95% CI [0.28, 0.64], p < 0.0001). These results suggest a spatially dependent link between Aβ-deposition and metabolism in healthy older adults, indicating a compensatory mechanism in early Alzheimer's. Additionally, Aβ-deposition was linked to changes in interregional neural communication.

Our study confirms previous findings on aging and offers new insights, particularly on the role of Aβ-deposition in healthy aging. We observed a linear increase in Aβ-deposition, alongside decreases in white matter integrity, cerebral blood flow, and glucose metabolism. Additionally, we identified a complex regional relationship between Aβ-deposition, glucose metabolism, and neural communication, possibly reflecting compensatory mechanisms.

Cardio-cerebral diseases (CCDs), encompassing conditions such as coronary heart disease, myocardial infarction, stroke, Alzheimer's disease, et al., represent a significant threat to human health and well-being. These diseases are often characterized by metabolic abnormalities and remodeling in the process of pathology. Glycolysis and hypoxia-induced lactate accumulation play critical roles in cellular energy dynamics and metabolic imbalances in CCDs. Lactylation, a post-translational modification driven by excessive lactate accumulation, occurs in both histone and non-histone proteins. It has been implicated in regulating protein function across various pathological processes in CCDs, including inflammation, angiogenesis, lipid metabolism dysregulation, and fibrosis. Targeting key proteins involved in lactylation, as well as the enzymes regulating this modification, holds promise as a therapeutic strategy to modulate disease progression by addressing these pathological mechanisms. This review provides a holistic picture of the types of lactylation and the associated modifying enzymes, highlights the roles of lactylation in different pathological processes, and synthesizes the latest clinical evidence and preclinical studies in a comprehensive view. We aim to emphasize the potential of lactylation as an innovative therapeutic target for preventing and treating CCD-related conditions.

The brain is a complex neural network whose functional dynamics offer valuable insights into behavioral performance and health. Advances in fMRI have provided a unique window into studying human brain networks, providing us with a powerful tool for clinical research. Yet many questions about the underlying correlates between spontaneous fMRI and neural activity remain poorly understood, limiting the impact of this research. Cross-species studies have proven essential in deepening our understanding of how neuronal activity is coupled to increases in local cerebral blood flow, changes in blood oxygenation, and the measured fMRI signal. In this article, we review some fundamental mechanisms implicated in neurovascular coupling. We then examine neurovascular coupling within the context of spontaneous cortical functional networks and their dynamics, summarizing key findings from mechanistic studies in rodents. In doing so, we highlight the nuances of the neurovascular coupling that ultimately influences the interpretation of derived hemodynamic functional networks, their dynamics, and the neural underpinnings they represent.

Schizophrenia (SZ) patients exhibit abnormal static and dynamic functional connectivity across various brain domains. We present a novel approach based on static and dynamic inter-network connectivity entropy (ICE), which represents the entropy of a given network's connectivity to all the other brain networks. This novel approach enables the investigation of how connectivity strength is heterogeneously distributed across available targets in both SZ patients and healthy controls. We analyzed fMRI data from 151 SZ patients and 160 demographically matched healthy controls (HC). Our assessment encompassed both static and dynamic ICE, revealing significant differences in the heterogeneity of connectivity levels across available functional brain networks between SZ patients and HC. These networks are associated with subcortical (SC), auditory (AUD), sensorimotor (SM), visual (VIS), cognitive control (CC), default mode network (DMN), and cerebellar (CB) functional brain domains. Elevated ICE observed in individuals with SZ suggests that patients exhibit significantly higher randomness in the distribution of time-varying connectivity strength across functional regions from each source network, compared to HC. C-means fuzzy clustering analysis of functional ICE correlation matrices revealed that SZ patients exhibit significantly higher occupancy weights in clusters with weak, low-scale functional entropy correlation, while the control group shows greater occupancy weights in clusters with strong, large-scale functional entropy correlation. K-means clustering analysis on time-indexed ICE vectors revealed that cluster with highest ICE have higher occupancy rates in SZ patients whereas clusters characterized by lowest ICE have larger occupancy rates for control group. Furthermore, our dynamic ICE approach revealed that in HC, the brain primarily communicates through complex, less structured connectivity patterns, with occasional transitions into more focused patterns. Individuals with SZ are significantly less likely to attain these more focused and structured transient connectivity patterns. The proposed ICE measure presents a novel framework for gaining deeper insight into mechanisms of healthy and diseased brain states and represents a useful step forward in developing advanced methods to help diagnose mental health conditions.

The study of mitochondrial dysfunction has become increasingly pivotal in elucidating the pathophysiology of various cerebral pathologies, particularly neurodegenerative disorders. Mitochondria are essential for cellular energy metabolism, regulation of reactive oxygen species (ROS), calcium homeostasis, and the execution of apoptotic processes. Disruptions in mitochondrial function, driven by factors such as oxidative stress, excitotoxicity, and altered ion balance, lead to neuronal death and contribute to cognitive impairments in several brain diseases. Mitochondrial dysfunction can arise from genetic mutations, ischemic events, hypoxia, and other environmental factors. This article highlights the critical role of mitochondrial dysfunction in the progression of neurodegenerative diseases and discusses the need for targeted therapeutic strategies to attenuate cellular damage, restore mitochondrial function, and enhance neuroprotection.

Chronic lung diseases such as Chronic Obstructive Pulmonary Disease, Interstitial Lung Disease (ILD), and Pulmonary Hypertension (PH) are characterized by progressive symptoms such as dyspnea, fatigue, and muscle weakness, often leading to physical inactivity, and reduced quality of life. Many patients also experience significantly impaired exercise tolerance. While pulmonary, cardiovascular, respiratory, and peripheral muscle dysfunction contribute to exercise limitations, recent evidence suggests that hypoxia and impairments in cerebral oxygenation may also play a role in exercise intolerance. This narrative review (i) summarizes studies investigating cerebral oxygenation responses during exercise in patients with different types of chronic lung diseases and (ii) discusses possible mechanisms behind the blunted cerebral oxygenation during exercise reported in many of these conditions; however, the extent of cerebral desaturation and the intensity at which it occurs can vary. These differences depend on the specific pathophysiology of the lung disease and the presence of comorbidities. Notably, reduced cerebral oxygenation during exercise in fibrotic-ILD has been linked with the development of dyspnea and early exercise termination. Understanding the effects of chronic lung disease on cerebral oxygenation during exercise may improve our understanding of exercise intolerance mechanisms and help identify therapeutic strategies to enhance brain health and exercise capacity in these patients.

Migraine prevalence in females is up to 3 times higher than in males and females show higher frequency, longer duration, and increased severity of headache attacks, but the reason for that difference is not known. This narrative review presents the main aspects of sex dimorphism in migraine prevalence and discusses the role of sex-related differences in mitochondrial homeostasis in that dimorphism. The gender dimension is also shortly addressed.

The imbalance between energy production and demand in the brain susceptible to migraine is an important element of migraine pathogenesis. Mitochondria are the main energy source in the brain and mitochondrial impairment is reported in both migraine patients and animal models of human migraine. However, it is not known whether the observed changes are consequences of primary disturbance of mitochondrial homeostasis or are secondary to the migraine-affected hyperexcitable brain. Sex hormones regulate mitochondrial homeostasis, and several reports suggest that the female hormones may act protectively against mitochondrial impairment, contributing to more effective energy production in females, which may be utilized in the mechanisms responsible for migraine progression. Migraine is characterized by several comorbidities that are characterized by sex dimorphism in their prevalence and impairments in mitochondrial functions. Mitochondria may play a major role in sexual dimorphism in migraine through the involvement in energy production, the dependence on sex hormones, and the involvement in sex-dependent comorbidities. Studies on the role of mitochondria in sex dimorphism in migraine may contribute to precise personal therapeutic strategies.

Two-photon phosphorescence lifetime microscopy has been a key tool for studying cerebral oxygenation in mice. However, the accuracy of the partial pressure of oxygen (pO2) measurements is affected by out-of-focus signal. In this work, we applied reconfigurable differential aberration imaging to characterize and correct for out-of-focus signal contamination in intravascular pO2 imaging. Our results show that signal contamination is higher in more oxygenated vessels and that it could be effectively removed using the proposed method.

Muscles are crucial for daily activities, and kidney transplant recipients (KTRs) often have reduced muscle mass and strength. We aimed to investigate the potential relationship of muscle mass and strength with physical health-related quality of life (HRQoL) in KTRs.

Data from the TransplantLines Biobank and Cohort Studies were used. Muscle mass was assessed using appendicular skeletal muscle mass index (ASMI) and 24-hour urinary creatinine excretion rate index (CERI). Muscle strength was assessed by handgrip strength index (HGSI). HRQoL was measured using Short Form 36 physical component score (PCS).

We included 751 KTRs (61% male; mean age, 56 ± 13 years, median of 3 years post-transplant). Ordinary least squares regression analyses demonstrated that lower ASMI, CERI, and HGSI were all nonlinearly associated with lower PCS, independent of potential confounders and each other. Below median values, ASMI, CERI, and HGSI were each associated with PCS; whereas above median values, associations were less pronounced. Compared to the 50th percentile, a decrease to the 10th percentile was associated with a change in PCS of -4.8% for ASMI (P = 0.011), of -5.1% for CERI (P = 0.008), and -13.2% for HGSI (P < 0.001), whereas an increase to the 90th percentile was associated with a change in PCS of only +0.7% for ASMI (P = 0.54), of +3.6% for CERI (P = 0.05), and -0.4% for HGSI (P = 0.73).

Low muscle mass and strength are potentially modifiable risk factors for impaired physical HRQoL in KTRs. The nonlinear associations suggest that KTRs with low muscle mass or strength may particularly benefit from (p)rehabilitation interventions to improve HRQoL.

Mitochondria are essential organelles that play crucial roles in various metabolic and signalling pathways. Proper neuronal function is highly dependent on the health of these organelles. Of note, the intricate structure of neurons poses a critical challenge for the transport and distribution of mitochondria to specific energy-intensive domains, such as synapses and dendritic appendages. When faced with chronic metabolic challenges and bioenergetic deficits, neurons undergo degeneration. Unsurprisingly, disruption of mitostasis, the process of maintaining cellular mitochondrial content and function within physiological limits, has been implicated in the pathogenesis of several age-associated neurodegenerative disorders. Indeed, compromised integrity and metabolic activity of mitochondria is a principal hallmark of neurodegeneration. In this review, we survey recent findings elucidating the role of impaired mitochondrial homeostasis and metabolism in the onset and progression of age-related neurodegenerative disorders. We also discuss the importance of neuronal mitostasis, with an emphasis on the major mitochondrial homeostatic and metabolic pathways that contribute to the proper functioning of neurons. A comprehensive delineation of these pathways is crucial for the development of early diagnostic and intervention approaches against neurodegeneration.

Introduction: Neuropsychiatric symptoms such as depression and anxiety are a significant burden on patients with multiple sclerosis (MS). Their pathophysiology is complex and yet to be fully understood. There is an urgent need for non-invasive treatments that directly target the brain and help patients with MS. One such possible treatment is transcranial direct current stimulation (tDCS), a popular and effective non-invasive brain stimulation technique. Methods: This mechanistic review explores the efficacy of tDCS in treating depression and anxiety in MS while focusing on the underlying mechanisms of action. Understanding these mechanisms is crucial, as neuropsychiatric symptoms in MS arise from complex neuroinflammatory and neurodegenerative processes. This review offers insights that may direct more focused and efficient therapeutic approaches by investigating the ways in which tDCS affects inflammation, brain plasticity, and neural connections. Searches were conducted using the PubMed/Medline, ResearchGate, Cochrane, and Google Scholar databases. Results: The literature search yielded 11 studies to be included in this review, with a total of 175 patients participating in the included studies. In most studies, tDCS did not significantly reduce depression or anxiety scores as the studied patients did not have elevated scores indicating depression and anxiety. In the few studies where the patients had scores indicating mild/moderate dysfunction, tDCS was more effective. The risk of bias in the included studies was assessed as moderate. Despite the null or near-null results, tDCS may still prove to be an effective treatment option for depression and anxiety in MS, because tDCS produces a neurobiological effect on the brain and nervous system. To facilitate further work, several possible mechanisms of action of tDCS have been reported, such as the modulation of the frontal-midline theta, reductions in neuroinflammation, the modulation of the HPA axis, and cerebral blood flow regulation. Conclusions: Although tDCS did not overall demonstrate positive effects in reducing depression and anxiety in the studied MS patients, the role of tDCS in this area should not be underestimated. Evidence from other studies indicates the effectiveness of tDCS in reducing depression and anxiety, but the studies included in this review did not include patients with sufficient depression or anxiety. Future studies are needed to confirm the effectiveness of tDCS in neuropsychiatric dysfunctions in MS.

The ongoing brain activity serves as a baseline that supports both internal and external cognitive processes. However, its precise nature remains unclear. Considering that people display various patterns of brain activity even when engaging in the same task, it is reasonable to believe that individuals possess their unique brain baseline pattern. Using spatial independent component analysis on a large sample of fMRI data from the Human Connectome Project (HCP), we found an individual-specific component which can be consistently extracted from either resting-state or different task states and is reliable over months. Compared to functional connectome fingerprinting, it is much more stable across different fMRI modalities. Its stability is closely related to high explained variance and is minimally influenced by factors such as noise, scan duration, and scan interval. We propose that this component underlying the ongoing activity represents an individual-specific baseline pattern of brain activity.

Neurovascular coupling (NVC) is the mechanism that drives the neurovascular response to neural activation, and NVC dysfunction has been implicated in various neurologic diseases. NVC is driven by (1) nonmetabolic feedforward mechanisms that are mediated by various signaling pathways and (2) metabolic feedback mechanisms that involve metabolic factors. However, the interplay between these feedback and feedforward mechanisms remains unresolved. We propose that feedforward mechanisms normally drive a swift, neural activation-induced regional cerebral blood flow (rCBF) overshoot, which floods the tissue beds, leading to local hypocapnia and hyperoxia. The feedback mechanisms are triggered by the resultant hypocapnia (not hyperoxia), which causes cerebral vasoconstriction in the neurovascular unit that counterbalances the rCBF overshoot and returns rCBF to a level that matches the metabolic activity. If feedforward mechanisms function improperly (eg, in a disease state), the rCBF overshoot, tissue-bed flooding, and local hypocapnia fail to occur or occur on a smaller scale. Consequently, the neural activation-related increase in metabolic activity results in local hypercapnia and hypoxia, both of which drive cerebral vasodilation and increase rCBF. Thus, feedback mechanisms ensure the brain milieu's stability when feedforward mechanisms are impaired. Our proposal integrates the feedforward and feedback mechanisms underlying NVC and suggests that these 2 mechanisms work like a fail-safe system, to a certain degree. We also discussed the difference between NVC and cerebral metabolic rate-CBF coupling and the clinical implications of our proposed framework.

Alzheimer's Disease (AD), and related dementias, represent a growing concern for the worldwide population given the increased numbers of people of advanced age. Marked by significant degradation of neurological tissues and critical processes, in addition to more specific factors such as the presence of amyloid plaques and neurofibrillary tangles in AD, robust discussion is ongoing regarding the precise mechanisms by which these diseases arise. One of the major interests in recent years has been the contribution of reactive oxygen species (ROS) and, particularly, the contribution of the ROS-generating NADPH Oxidase proteins. NADPH Oxidase 2 (NOX2), the prototypical member of the family, represents a particularly interesting target for study given its close association with vascular and inflammatory processes in all tissues, including the brain, and the association of these processes with AD development and progression. In this review, we discuss the most relevant and recent work regarding the contribution of NOX2 to AD progression in neuronal, microglial, and cerebrovascular signaling. Furthermore, we will discuss the most promising NOX2-targeted therapeutics for potential AD management and treatment.

The placenta plays influential role in the fetal development of mammals. But how the metabolic need of the fetal organs is related to that of the placenta, and whether this relationship is influenced by the sex of the fetus remain poorly understood.

This study used pigs to investigate metabolomic signatures of male and female fetal organs, and determine the relevance of gene expression of the placenta and brain to the metabolism of peripheral organs.

Untargeted metabolomics analysis was performed with the day-45 placenta, kidney, heart, liver, lung and brain of male and female pig fetuses to model sex differences in the metabolism of the peripheral organs relative to that of the brain and placenta. Transcriptomic analysis was performed to investigate the expression of metabolic genes in the placenta and fetal brain of both sexes.

The results of this study show that the fetoplacental metabolic regulation was not only influenced by the fetal sex but also dependent on the metabolic requirement of  the individual organs of the fetus. Neural network modeling of metabolomics data revealed differential relationship of the metabolic changes of the peripheral organs with the placenta and fetal brain between males and females. RNA sequencing further showed that genes associated with the metabolism of the peripheral organs were differentially expressed in the placenta and fetal brain.

The findings of this study suggest a regulatory role of the fetal brain and placenta axis in the sex-bias metabolism of the peripheral organs.

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare metabolic encephalopathy with a wide variety of clinical phenotypes. In the present study, 15 patients diagnosed with GLUT1-DS were selected, all of whom had obvious clinical manifestations and complete genetic testing. Their clinical data and genetic reports were collated. All patients were provided with a ketogenic diet (KD) and an improvement in their symptoms was observed during a follow-up period of up to 1 year. The results revealed that the 15 cases had clinical symptoms, such as convulsions or dyskinesia. Although none had a cerebrospinal fluid/glucose ratio <0.4, the genetic report revealed that all had the solute carrier family 2 member 1 gene variant, and their clinical symptoms basically improved following the use of the KD. GLUT1-DS is a genetic metabolic disease that causes a series of neurological symptoms due to glucose metabolism disorders in the brain. Low glucose levels in cerebrospinal fluid and genetic testing are key diagnostic criteria, and the KD is a highly effective treatment option. By summarizing and analyzing patients with GLUT1-DS, summarizing clinical characteristics and expanding their gene profile, the findings of the present study may be of clinical significance for the early recognition and diagnosis of the disease, so as to conduct early treatment and shorten the duration of brain energy deficiency. This is of utmost importance for improving the prognosis and quality of life of affected children.

Neuronal cells are highly specialized cells and have a specific metabolic profile to support their function. It has been demonstrated that the metabolic profiles of different cells/tissues undergo significant reprogramming with advancing age, which has often been considered a contributing factor towards aging-related diseases including Alzheimer's (AD) and Parkinson's (PD) diseases. However, it is unclear if the metabolic changes associated with normal aging predispose neurons to disease conditions or a distinct set of metabolic alterations happen in neurons in AD or PD which might contribute to disease pathologies. To decipher the changes in neuronal metabolism with age, in AD, or in PD, we performed high-throughput steady-state metabolite profiling on heads in wildtype Drosophila and in Drosophila models relevant to AD and PD. Intriguingly, we found that the spectrum of affected metabolic pathways is dramatically different between normal aging, Tau, or Synuclein overexpressing neurons. Genetic targeting of the purine and glutamate metabolism pathways, which were dysregulated in both old age and disease conditions partially rescued the neurodegenerative phenotype associated with the overexpression of wildtype and mutant tau. Our findings support a "two-hit model" to explain the pathological manifestations associated with AD where both aging- and Tau/Synuclein- driven metabolic reprogramming events cooperate with each other, and targeting both could be a potent therapeutic strategy.

Our understanding of the relationship between neural activity and psychological states has advanced greatly in recent decades. But we are still unable to explain conscious experience in terms of physical processes occurring in our brains.

This paper introduces a conceptual framework that may contribute to an explanation. All physical processes entail the transfer, transduction, and transformation of energy between portions of matter as work is performed in material systems. If the production of consciousness in nervous systems is a physical process, then it must entail the same. Here the nervous system, and the brain in particular, is considered as a material system that transfers, transduces, and transforms energy as it performs biophysical work.

Evidence from neuroscience suggests that conscious experience is produced in the organic matter of nervous systems when they perform biophysical work at classical and quantum scales with a certain level of dynamic complexity or organization. An empirically grounded, falsifiable, and testable hypothesis is offered to explain how energy processing in nervous systems may produce conscious experience at a fundamental physical level.

The stability-plasticity dilemma remains a critical challenge in developing artificial intelligence (AI) systems capable of continuous learning. This perspective paper presents a novel approach by drawing inspiration from the mammalian hippocampus-cortex system. We elucidate how this biological system's ability to balance rapid learning with long-term memory retention can inspire novel AI architectures. Our analysis focuses on key mechanisms, including complementary learning systems and memory consolidation, with emphasis on recent discoveries about sharp-wave ripples and barrages of action potentials. We propose innovative AI designs incorporating dual learning rates, offline consolidation, and dynamic plasticity modulation. This interdisciplinary approach offers a framework for more adaptive AI systems while providing insights into biological learning. We present testable predictions and discuss potential implementations and implications of these biologically inspired principles. By bridging neuroscience and AI, our perspective aims to catalyze advancements in both fields, potentially revolutionizing AI capabilities while deepening our understanding of neural processes.

Dopaminergic neurons from the substantia nigra pars compacta (SNc) have a higher susceptibility to aging-related degeneration, compared to midbrain dopaminergic cells present in the ventral tegmental area (VTA); the death of dopamine neurons in the SNc results in Parkinson´s disease (PD). In addition to increased loss by aging, dopaminergic neurons from the SNc are more prone to cell death when exposed to genetic or environmental factors, that either interfere with mitochondrial function, or cause an increase of oxidative stress. The oxidation of dopamine is a contributing source of reactive oxygen species (ROS), but this production is not enough to explain the differences in susceptibility to degeneration between SNc and VTA neurons.

In this review we aim to highlight the intrinsic differences between SNc and VTA dopamine neurons, in terms of gene expression, calcium oscillations, bioenergetics, and ROS responses. Also, to describe the changes in the pentose phosphate pathway and the induction of apoptosis in SNc neurons during aging, as related to the development of PD.

Recent work showed that neurons from the SNc possess intrinsic characteristics that result in metabolic differences, related to their intricate morphology, that render them more susceptible to degeneration. In particular, these neurons have an elevated basal energy metabolism, that is required to fulfill the demands of the constant firing of action potentials, but at the same time, is associated to higher ROS production, compared to VTA cells. Finally, we discuss how mutations related to PD affect metabolic pathways, and the related mechanisms, as revealed by metabolomics.

Heterotrimeric extracellular matrix proteins laminins are mostly deposited at basal membranes and are important in repair and neoplasia. Here, we localize laminin beta 2 (LAMB2) at the sites of blood-brain barrier (BBB). Microvasculature (MV) of normal brain is endowed with complete LAMB2 coverage. In contrast, its cognate protein laminin beta 1 (LAMB1) is absent in MV of normal brain but emerges at the sprouting tip of a growing vessels. Similarly, vascular proliferation in high-grade gliomas (HGG) is accompanied by marked overexpression of LAMB1, whereas LAMB2 shows deficient deposition. We find that many brain pathologies with presence of post-gadolinium enhancement (PGE) on magnetic resonance imaging (MRI) show disruption of LAMB2 vascular ensheathment. Inhibition of vascular endothelial growth factor signaling in HGG blocks angiogenesis, suppresses PGE in HGG, prevents expression of LAMB1, and restores LAMB2 vascular coverage. Analysis of single-cell RNA sequencing (scRNA-seq) databases shows that in quiescent brain LAMB2 is predominantly expressed by BBB-associated pericytes (PCs) and endothelial cells (ECs), whereas neither cell types produce LAMB1. In contrast, in HGG, both LAMB1 and 2 are overexpressed by endothelial precursor cells, a phenotypically unique immature group, specific to proliferating hyperplastic MV.

Mitochondria play a crucial role in brain aging due to their involvement in bioenergetics, neuroinflammation and brain steroid synthesis. Mitochondrial dysfunction is linked to age-related neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. We investigated changes in the activities of the electron transport chain (ETC) complexes in normally aging baboon brains and determined how these changes relate to donor sex, morning cortisol levels, and walking speed. Using a novel approach, we assessed mitochondrial bioenergetics from frozen prefrontal cortex (PFC) tissues from a large cohort (60 individuals) of well-characterized aging baboons (6.6-22.8 years, approximately equivalent to 26.4-91.2 human years). Aging was associated with a decline in mitochondrial ETC complexes in the PFC, which was more pronounced when activities were normalized for citrate synthase activity, suggesting that the decline in respiration is predominantly driven by changes in the specific activity of individual complexes rather than changes in mitochondrial number. Moreover, when donor sex was used as a covariate, we found that mitochondrial respiration was preserved with age in females, whereas males showed significant loss of ETC activity with age. Males had higher activities of each individual ETC complex and greater lactate dehydrogenase activity relative to females. Circulating cortisol levels correlated only with complex II-linked respiration in males. We also observed a robust positive predictive relationship between walking speed and respiration linked to complexes I, III, and IV in males but not in females. This data reveals a previously unknown link between aging and bioenergetics across multiple tissues linking frailty and bioenergetic function. This study highlights a potential molecular mechanism for sexual dimorphism in brain resilience and suggests that in males changes in PFC bioenergetics contribute to reduced motor function with age.

Multidimensional reconstruction of brain attractors from electroencephalography (EEG) data enables the analysis of geometric complexity and interactions between signals in state space. Utilizing resting-state data from young and older adults, we characterize periodic (traditional frequency bands) and aperiodic (broadband exponent) attractors according to their geometric complexity and shared dynamical signatures, which we refer to as a geometric cross-parameter coupling. Alpha and aperiodic attractors are the least complex, and their global shapes are shared among all other frequency bands, affording alpha and aperiodic greater predictive power. Older adults show lower geometric complexity but greater coupling, resulting from dedifferentiation of gamma activity. The form and content of resting-state thoughts were further associated with the complexity of attractor dynamics. These findings support a process-developmental perspective on the brain's dynamic core, whereby more complex information differentiates out of an integrative and global geometric core.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease that results in the loss of motor neurons and severe skeletal muscle atrophy. The etiology of ALS is linked to skeletal muscle, which can activate a retrograde signaling cascade that destroys motor neurons. This is why satellite cells and mitochondria play a crucial role in the health and performance of skeletal muscles. This review presents current knowledge on the involvement of mitochondrial dysfunction, skeletal muscle atrophy, muscle satellite cells, and neuromuscular junction (NMJ) in ALS. It also discusses current therapeutic strategies, including exercise, drugs, stem cells, gene therapy, and the prospective use of mitochondrial transplantation as a viable therapeutic strategy.

Post-transcriptional tRNA modifications contribute to the decoding efficiency of tRNAs by supporting codon recognition and tRNA stability. Recent work shows that the molecular and cellular functions of tRNA modifications and tRNA-modifying-enzymes are linked to brain development and neurological disorders. Lack of these modifications affects codon recognition and decoding rate, promoting protein aggregation and translational stress response pathways with toxic consequences to the cell. In this review, we discuss the peculiarity of local translation in neurons, suggesting a role for fine-tuning of translation performed by tRNA modifications. We provide several examples of tRNA modifications involved in physiology and pathology of the nervous system, highlighting their effects on protein translation and discussing underlying mechanisms, like the unfolded protein response (UPR), ribosome quality control (RQC), and no-go mRNA decay (NGD), which could affect neuronal functions. We aim to deepen the understanding of the roles of tRNA modifications and the coordination of these modifications with the protein translation machinery in the nervous system.

Previous imaging studies have demonstrated that diabetic retinopathy (DR) is linked to structural and functional abnormalities in the brain. However, the extent to which DR patients exhibit abnormal neurovascular coupling remains largely unknown.

Thirty-one patients with DR and 31 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging (rs-fMRI) to calculate functional connectivity strength (FCS) and arterial spin-labeling imaging (ASL) to calculate cerebral blood flow (CBF). The study compared CBF-FCS coupling across the entire grey matter and CBF/FCS ratios (representing blood supply per unit of connectivity strength) per voxel between the two groups. Additionally, a support vector machine (SVM) method was employed to differentiate between diabetic retinopathy (DR) patients and healthy controls (HC).

In DRpatients compared to healthy controls, there was a reduction in CBF-FCS coupling across the entire grey matter. Specifically, DR patients exhibited elevated CBF/FCS ratios primarily in the primary visual cortex, including the right calcarine fissure and surrounding cortex. On the other hand, reduced CBF/FCS ratios were mainly observed in premotor and supplementary motor areas, including the left middle frontal gyrus.

An elevated CBF/FCS ratio suggests that patients with DR may have a reduced volume of gray matter in the brain. A decrease in its ratio indicates a decrease in regional CBF in patients with DR. These findings suggest that neurovascular decoupling in the visual cortex, as well as in the supplementary motor and frontal gyrus, may represent a neuropathological mechanism in diabetic retinopathy.

Gabapentinoid drugs (pregabalin and gabapentin) have been successfully used in the treatment of neuropathic pain and in focal seizure prevention. Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue, oxidative stress, and inflammation, which matches the mechanism of action via voltage-gated calcium channels. In this review, we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids. We systematically summarize the preclinical and clinical research on gabapentinoids in stroke, including ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, seizures after stroke, cortical spreading depolarization after stroke, pain after stroke, and nerve regeneration after stroke. This review also discusses the potential targets of gabapentinoids in stroke; however, the existing results are still uncertain regarding the effect of gabapentinoids on stroke and related diseases. Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke. Therefore, gabapentinoids have both opportunities and challenges in the treatment of stroke.

The mitochondrial translocator protein 18 kDa (TSPO) has been linked to functions from steroidogenesis to regulation of cellular metabolism and is an attractive therapeutic target for chronic CNS inflammation. Studies in Leydig cells and microglia indicate that TSPO function may vary between cells depending on their specialized roles. Astrocytes are critical for providing trophic and metabolic support in the brain. Recent work has highlighted that TSPO expression increases in astrocytes under inflamed conditions and may drive astrocyte reactivity. Relatively little is known about the role TSPO plays in regulating astrocyte metabolism and whether this protein is involved in immunometabolic processes in these cells. Using TSPO-deficient (TSPO-/-) mouse primary astrocytes in vitro (MPAs) and a human astrocytoma cell line (U373 cells), we performed extracellular metabolic flux analyses. We found that TSPO deficiency reduced basal cellular respiration and attenuated the bioenergetic response to glucopenia. Fatty acid oxidation was increased, and lactate production was reduced in TSPO-/- MPAs and U373 cells. Co-immunoprecipitation studies revealed that TSPO forms a complex with carnitine palmitoyltransferase 1a in U373 and MPAs, presenting a mechanism wherein TSPO may regulate FAO in these cells. Compared to TSPO+/+ cells, in TSPO-/- MPAs we observed attenuated tumor necrosis factor release following 3 h lipopolysaccharide (LPS) stimulation, which was enhanced at 24 h post-LPS stimulation. Together these data suggest that while TSPO acts as a regulator of metabolic flexibility, TSPO deficiency does not appear to modulate the metabolic response of MPAs to inflammation, at least in response to the model used in this study.

Aging is a complex biological process with sexually dimorphic aspects. Although cognitive aging of Caenorhabditis elegans hermaphrodites has been studied, less is known about cognitive decline in males. We found that cognitive aging has both sex-shared and sex-dimorphic characteristics, and we identified neuron-specific age-associated sex-differential targets. In addition to sex-shared neuronal aging genes, males differentially downregulate mitochondrial metabolic genes and upregulate GPCR genes with age, while the X chromosome exhibits increased gene expression in hermaphrodites and altered dosage compensation complex expression with age, indicating possible X chromosome dysregulation that contributes to sexual dimorphism in cognitive aging. Finally, the sex-differentially expressed gene hrg-7, an aspartic-type endopeptidase, regulates male cognitive aging but does not affect hermaphrodites' behaviors. These results suggest that males and hermaphrodites exhibit different age-related neuronal changes. This study will strengthen our understanding of sex-specific vulnerability and resilience and identify pathways to target with treatments that could benefit both sexes.

Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology.

On November 21, 2023, we conducted a search on Web of Science (WOS), restricting the document type to articles or reviews and language to English. Following a meticulous selection process involving three researchers, we identified the literature to be included in our analysis. Subsequently, we employed Microsoft Office Excel programs, R, VOSviewer, Scimago Graphica, and CiteSpace software to conduct visualization analysis of basic information and trends regarding journals, countries/regions, and influential authors, institutions, keywords, and papers.

As of November 21, 2023, relevant literature has been published in 71 journals across 27 countries/regions. This corpus comprises contributions from 576 authors affiliated with 220 institutions, encompassing 865 keywords and referencing 6065 scholarly articles. CEPHALALGIA stands out as the most influential journal in this field, while authors PIETROBON D and DALKARA T have significant impact. The United States is highly influential, with CNR and UNIV PADUA emerging as highly influential institutions. The predominant category is Neurosciences.

Future investigators may continue to focus on migraines with aura, familial hemiplegic migraine (FHM), and the crucial calcitonin gene-related peptide (CGRP) system. Employing advanced observational techniques, such as imaging, researchers should pay attention to cellular and tissue structures, such as microglia and the trigeminal ganglion, as well as mechanisms involving inflammation and central sensitization. Moreover, animal models are paramount in obtaining high-quality evidence.

Migraine, as a prevalent neurologic disorder, involves intricate and yet incompletely elucidated pathophysiological mechanisms. A plethora of research findings underscores the pivotal role played by astrocytes in the progression of migraines. In order to elucidate the current advances and directions in research pertaining to astrocytes in migraines, we conducted bibliometric analysis of relevant literature and visualized the results. Subsequently, we expound upon these findings to contribute to the evolving understanding of the role of astrocytes in migraine pathophysiology.

On November 21, 2023, we conducted a search on Web of Science (WOS), restricting the document type to articles or reviews and language to English. Following a meticulous selection process involving three researchers, we identified the literature to be included in our analysis. Subsequently, we employed Microsoft Office Excel programs, R, VOSviewer, Scimago Graphica, and CiteSpace software to conduct visualization analysis of basic information and trends regarding journals, countries/regions, and influential authors, institutions, keywords, and papers.

As of November 21, 2023, relevant literature has been published in 71 journals across 27 countries/regions. This corpus comprises contributions from 576 authors affiliated with 220 institutions, encompassing 865 keywords and referencing 6065 scholarly articles. CEPHALALGIA stands out as the most influential journal in this field, while authors PIETROBON D and DALKARA T have significant impact. The United States is highly influential, with CNR and UNIV PADUA emerging as highly influential institutions. The predominant category is Neurosciences.

Future investigators may continue to focus on migraines with aura, familial hemiplegic migraine (FHM), and the crucial calcitonin gene-related peptide (CGRP) system. Employing advanced observational techniques, such as imaging, researchers should pay attention to cellular and tissue structures, such as microglia and the trigeminal ganglion, as well as mechanisms involving inflammation and central sensitization. Moreover, animal models are paramount in obtaining high-quality evidence.