Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Jan 26, 2020; 12(1): 8-24
Published online Jan 26, 2020. doi: 10.4252/wjsc.v12.i1.8
Regeneration of the central nervous system-principles from brain regeneration in adult zebrafish
Alessandro Zambusi, Jovica Ninkovic
Alessandro Zambusi, Jovica Ninkovic, Helmholtz Center Munich, Biomedical Center, Inst Stem Cell Res, Institute of Stem Cell Research, Department of Cell Biology and Anatomy, University of Munich, Planegg 82152, Germany
Author contributions: All authors contributed equally to this paper in conception and design of the study; literature review and analysis; drafting, critical revision and editing; and approval of the final version.
Supported by the German Research foundation (DFG), No. SFB 870.
Conflict-of-interest statement: The authors declare no potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Jovica Ninkovic, PhD, Professor, Helmholtz Center Munich, Biomedical Center, Inst Stem Cell Res, Institute of Stem Cell Research, University of Munich, Grosshadernerstrasse 9, Planegg 82152, Germany. ninkovic@helmholtz-muenchen.de
Received: August 9, 2019
Peer-review started: August 9, 2019
First decision: August 30, 2019
Revised: November 25, 2019
Accepted: December 13, 2019
Article in press: December 13, 2019
Published online: January 26, 2020
Abstract

Poor recovery of neuronal functions is one of the most common healthcare challenges for patients with different types of brain injuries and/or neurodegenerative diseases. Therapeutic interventions face two major challenges: (1) How to generate neurons de novo to replenish the neuronal loss caused by injuries or neurodegeneration (restorative neurogenesis) and (2) How to prevent or limit the secondary tissue damage caused by long-term accumulation of glial cells, including microglia, at injury site (glial scar). In contrast to mammals, zebrafish have extensive regenerative capacity in numerous vital organs, including the brain, thus making them a valuable model to improve the existing therapeutic approaches for human brain repair. In response to injuries to the central nervous system (CNS), zebrafish have developed specific mechanisms to promote the recovery of the lost tissue architecture and functionality of the damaged CNS. These mechanisms include the activation of a restorative neurogenic program in a specific set of glial cells (ependymoglia) and the resolution of both the glial scar and inflammation, thus enabling proper neuronal specification and survival. In this review, we discuss the cellular and molecular mechanisms underlying the regenerative ability in the adult zebrafish brain and conclude with the potential applicability of these mechanisms in repair of the mammalian CNS.

Keywords: Zebrafish, Central nervous system, Brain injury, Glial scar, Regeneration, Restorative neurogenesis, Neural stem cells, Inflammation

Core tip: Poor recovery of neuronal functions is one of the most common healthcare challenges for patients with different types of brain injuries. In contrast to mammals, zebrafish have developed specific mechanisms to activate a restorative neurogenic program in a specific set of glial cells (ependymoglia) and to resolve both the glial scar and inflammation, thus enabling proper neuronal specification and survival. In this review, we discuss these mechanisms and their potential applicability for the repair of the mammalian central nervous system.