Gluck Lauren, Gerstein Brittany, Kaunzner Ulrike W
Montefiore Medical Center, 1250 Waters Place Tower 2, Bronx, NY 10461, USA.
Weill-Cornell-Medicine, Department of Neurology, 1305 York Avenue, New York City, 10021, USA.
Neurotherapeutics. 2025 May 9:e00583. doi: 10.1016/j.neurot.2025.e00583.
The central nervous system (CNS), comprising the brain, spinal cord, and optic nerve, has limited regenerative capacity, posing significant challenges in treating neurological disorders. Recent advances in neuroscience and neurotherapeutics have introduced promising strategies to stimulate CNS repair, particularly in the context of neurodegenerative diseases such as multiple sclerosis. This review explores the complex interplay between inflammation, demyelination, and remyelination possibilities. Glial cells, including oligodendrocyte precursors, oligodendrocytes, astrocytes and microglia play dual roles in injury response, with reactive gliosis promoting repair but also potentially inhibiting recovery through glial scar formation. There is also an emphasis on axonal regeneration, axonal sprouting and stem cell therapies. We highlight the role of neuroplasticity in recovery post-injury and the limited regenerative potential of axons in the CNS due to inhibitory factors such as myelin-associated inhibitors. Moreover, neurotrophic factors support neuronal survival and axonal growth, while stem cell-based approaches offer promise for replacing lost neurons and glial cells. However, challenges such as stem cell survival, integration, and risk of tumor formation remain. Furthermore, we examine the role of neurogenesis in CNS repair and the remodeling of the extracellular matrix, which can facilitate regeneration. Through these diverse mechanisms, ongoing research aims to overcome the intrinsic and extrinsic barriers to CNS repair and advance therapeutic strategies for neurological diseases.
中枢神经系统（CNS）由脑、脊髓和视神经组成，其再生能力有限，这给神经系统疾病的治疗带来了重大挑战。神经科学和神经治疗学的最新进展引入了有前景的策略来刺激中枢神经系统修复，特别是在多发性硬化症等神经退行性疾病的背景下。本综述探讨了炎症、脱髓鞘和再髓鞘化可能性之间的复杂相互作用。胶质细胞，包括少突胶质细胞前体、少突胶质细胞、星形胶质细胞和小胶质细胞在损伤反应中发挥双重作用，反应性胶质增生促进修复，但也可能通过胶质瘢痕形成抑制恢复。文中还强调了轴突再生、轴突发芽和干细胞疗法。我们强调了神经可塑性在损伤后恢复中的作用，以及由于髓磷脂相关抑制剂等抑制因素，中枢神经系统中轴突的再生潜力有限。此外，神经营养因子支持神经元存活和轴突生长，而基于干细胞的方法为替代丢失的神经元和胶质细胞带来了希望。然而，干细胞存活、整合和肿瘤形成风险等挑战仍然存在。此外，我们研究了神经发生在中枢神经系统修复和细胞外基质重塑中的作用，细胞外基质重塑可以促进再生。通过这些不同的机制，正在进行的研究旨在克服中枢神经系统修复的内在和外在障碍，并推进神经系统疾病的治疗策略。
