Zambusi Alessandro, Ninkovic Jovica
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.
World J Stem Cells. 2020 Jan 26;12(1):8-24. doi: 10.4252/wjsc.v12.i1.8.
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 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.
神经元功能恢复不佳是不同类型脑损伤和/或神经退行性疾病患者最常见的医疗挑战之一。治疗干预面临两大挑战：（1）如何生成神经元以补充由损伤或神经退行性变导致的神经元损失（修复性神经发生）；（2）如何预防或限制由损伤部位（胶质瘢痕）的胶质细胞（包括小胶质细胞）长期积累所引起的继发性组织损伤。与哺乳动物不同，斑马鱼在包括大脑在内的许多重要器官中具有广泛的再生能力，因此使其成为改进现有人类脑修复治疗方法的宝贵模型。针对中枢神经系统（CNS）损伤，斑马鱼已形成特定机制来促进受损中枢神经系统丢失的组织结构和功能的恢复。这些机制包括在一组特定的胶质细胞（室管膜胶质细胞）中激活修复性神经发生程序，以及消除胶质瘢痕和炎症，从而实现适当的神经元特化和存活。在本综述中，我们讨论成年斑马鱼大脑再生能力背后的细胞和分子机制，并总结这些机制在哺乳动物中枢神经系统修复中的潜在适用性。
