Patel Jai Chand, Shukla Meenakshi, Shukla Manish
Department of Genetics Cell Biology & Anatomy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Neurosurgery, Penn State Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Cells. 2025 Jun 18;14(12):918. doi: 10.3390/cells14120918.
The central nervous system (CNS) is highly susceptible to damage due to its limited ability to regenerate. Injuries to the CNS, whether from trauma, ischemia, or neurodegenerative diseases, disrupt both cellular and vascular structures, leading to immediate (primary) and subsequent (secondary) damage. Primary damage involves the physical disruption of cells and blood vessels, weakening the blood-brain barrier (BBB) and triggering excitotoxicity and calcium overload. Secondary damage develops over hours to days and is marked by ionic imbalance, mitochondrial dysfunction, oxidative stress, and chronic inflammation, which further aggravates tissue damage. Inflammation plays a dual role: acute inflammation helps in repair, while chronic inflammation accelerates neurodegeneration. Microglia and astrocytes play key roles in this inflammatory response, with M1-like microglia promoting pro-inflammatory responses and M2-like microglia supporting anti-inflammatory and repair processes. Neurodegenerative diseases are characterized by the accumulation of misfolded proteins such as Tau, amyloid-beta, TDP-43, and α-synuclein, which impair cellular function and lead to neuronal loss. Neurodegenerative diseases are characterized by the accumulation of misfolded proteins and influenced by genetic risk factors (e.g., ). Despite the CNS's limited regenerative abilities, processes like synaptogenesis, neurogenesis, axonal regeneration, and remyelination offer potential for recovery. Therapeutic approaches aim to target inflammatory pathways, enhance repair mechanisms, and develop neuroprotective treatments to counter excitotoxicity, oxidative stress, and apoptosis. Advances in stem cell therapy, gene therapy, and personalized medicine hold promise for improving outcomes. Future research should focus on combining strategies, utilizing advanced technologies, and conducting translational studies to bridge the gap between preclinical research and clinical application. By better understanding and leveraging the complex processes of CNS injury and repair, researchers hope to develop effective therapies to restore function and enhance the quality of life for individuals with CNS disorders.
中枢神经系统（CNS）因其再生能力有限而极易受损。中枢神经系统的损伤，无论是由创伤、缺血还是神经退行性疾病引起，都会破坏细胞和血管结构，导致即时（原发性）和后续（继发性）损伤。原发性损伤涉及细胞和血管的物理破坏，削弱血脑屏障（BBB）并引发兴奋性毒性和钙超载。继发性损伤在数小时至数天内发展，其特征是离子失衡、线粒体功能障碍、氧化应激和慢性炎症，这会进一步加重组织损伤。炎症起着双重作用：急性炎症有助于修复，而慢性炎症会加速神经退行性变。小胶质细胞和星形胶质细胞在这种炎症反应中起关键作用，M1样小胶质细胞促进促炎反应，M2样小胶质细胞支持抗炎和修复过程。神经退行性疾病的特征是错误折叠蛋白如Tau、淀粉样β蛋白、TDP - 43和α -突触核蛋白的积累，这些蛋白会损害细胞功能并导致神经元丢失。神经退行性疾病的特征是错误折叠蛋白的积累，并受遗传风险因素（例如）影响。尽管中枢神经系统的再生能力有限，但诸如突触形成、神经发生、轴突再生和髓鞘再生等过程为恢复提供了潜力。治疗方法旨在针对炎症途径、增强修复机制，并开发神经保护疗法以对抗兴奋性毒性、氧化应激和细胞凋亡。干细胞治疗、基因治疗和个性化医学的进展有望改善治疗效果。未来的研究应侧重于结合策略、利用先进技术并进行转化研究，以弥合临床前研究与临床应用之间的差距。通过更好地理解和利用中枢神经系统损伤和修复的复杂过程，研究人员希望开发出有效的疗法来恢复功能并提高中枢神经系统疾病患者的生活质量。
