Biochemical changes in the injured brain

Table 1 Serum and cerebrospinal fluid biomarkers of cerebral injury

	Structure effected	Findings in brain injury
		Cerebro spinal fluid	Blood/serum
Tau protein	Axon	Levels peak 4-8 d after injury[111,112]	Elevated levels in hypoxic injury[113,114]
Myelin basic protein	Axon	Precise measurement difficult[115]	Elevated levels in brain injury[116]
γ-enolase	Neuron	Confounded by blood contaminated CSF[117]	Serum levels are very sensitive to lysis of RBC in blood contaminated CSF[117], elevated levels in brain injury[116]
S-100 β	Astrolglial cells	Elevated levels but less sensitive[108]	Confounded by release from extracerebral tissue[118]
GFAP	Astroglial cells	Elevated levels but less sensitive[107,108]	Serum levels correlate with changes in brain imaging[119], no extracerebral sources detected[120]
UCH-L1	Neuron	NA	Only one pilot study[98]

GFAP: Glial fibrillary acidic protein; UCH-L1: Ubiquitin c terminal hydrolase; NA: Not available; CSF: Cerebrospinal fluid; RBC: Red blood cell.

Table 2 The components monitored by cerebral microdialysis and their clinical implications

Variable	Normal levels (at a flow rate of 0.3 μL/min)	Clinical implications
Lactate	2.9 ± 0.9 mmol/L	Increased levels seen in ischemia and hyperglycolysis[121-123]
Pyruvate	166 ± 47 μmol/L	Decreased levels seen in ischemia and hypoxic conditions[124,125]
L/P ratio	Normal value-20	Value > 25 - metabolic crisis[124]
		Type 1-lactate increased, pyruvate decreased, signifying ischemia
		Type 2-raised LPR due to primarily decreased pyruvate level, seen in glycolysis failure or shunting of glucose to alternative metabolic pathways[125]
Glycerol	82 ± 4 μmol/L	One of the constituents of the cell membranes
		An increase in levels signifies cell damage[124]
Glutamate	16 ± 16 μmol/L	Marker of excitotoxicity[124]
Glucose	1.7 ± 0.9 mmol/L	Changes in blood flow or metabolism cause disproportionate changes in brain glucose
		Affected by ischaemia, hyperaemia, hyperglycaemia, hypermetabolism and hypometabolism[124]

Table 3 Cerebral microdialysis implications in clinical scenarios

Clinical condition	CMD implications
Traumatic brain injury	Helpful in optimising therapy in neuro-ICUs as a component of multi-modality monitoring
	Helpful in indivisualising management on the basis of cerebral perfusion pressure targets and assessment of response to medical and surgical interventions[126,127]
	Predictor of severity, neurological outcome and long-term anatomical aberrations in the injured brain[128-130]
	Detection and management of glycemic perturbations of the injured brain[131,132]
	Predicting long-term anatomical alteration[133]
Subarachnoid haemorrhage	Detection of ischemic changes during aneurysm clipping[134]
	Specific for the detection of delayed ischaemic neurological deficit[135-138]
	Prognostication of SAH patients[139,140]
Acute ischaemic stroke	Detecting development of oedema of the infarcted tissue[141]
	Monitoring effects of decompression hemicraniectomy and hypothermia in stroke patients[142,143]
Brain tumours	Neurobiochemistry of brain tumours[144,145]
	Biochemical changes during treatment
	Drug pharmacokinetics study[146]
	Monitoring of drug effect
	Development of tumor drug delivery systems[147,148]
Epilepsy	Study of biochemical milieu of epileptic focus[149]
Other applications	Study of the perihaemorrhagic zone in intracranial hemorrhage[150,151]
	Study of biochemical changes and novel therapeutic options in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease

CMD: Cerebral microdialysis; SAH: Subarachnoid hemorrhage; ICU: Intensive care unit.