Li Chun, Luo Yuping, Li Siguang
Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Neural Regen Res. 2025 Apr 29. doi: 10.4103/NRR.NRR-D-24-01324.
Stroke, particularly ischemic stroke, is the leading cause of long-term disability and mortality worldwide. It occurs due to the occlusion of the cerebral arteries, which significantly reduces the delivery of blood, oxygen, and essential nutrients to brain tissues. This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death. Recent studies have clarified the multifactorial pathogenesis of ischemic stroke, highlighting the roles of energy failure, excitotoxicity, oxidative stress, neuroinflammation, and apoptosis. This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke. Additionally, we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke, including the interplay of apoptosis, autophagy, pyroptosis, ferroptosis, and necrosis, which collectively influence neuronal fate. We also discussed advancements in neuroprotective therapeutics, encompassing a range of interventions from pharmacological modulation to stem cell-based therapies, aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke. Despite these advancements, challenges remain in translating mechanistic insights into effective clinical therapies. Although neuroprotective strategies have shown promise in preclinical models, their efficacy in human trials has been inconsistent, often due to the complex pathology of ischemic stroke and the timing of interventions. In conclusion, this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia. It sheds light on cutting-edge advancements in potential neuroprotective therapeutics, underscores the promise of regenerative medicine, and offers a forward-looking perspective on potential clinical breakthroughs. The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
中风，尤其是缺血性中风，是全球长期残疾和死亡的主要原因。它是由于脑动脉闭塞所致，这会显著减少向脑组织输送血液、氧气和必需营养物质。这种剥夺引发一系列细胞事件，最终导致神经元死亡。最近的研究已经阐明了缺血性中风的多因素发病机制，突出了能量衰竭、兴奋性毒性、氧化应激、神经炎症和细胞凋亡的作用。这篇综述旨在全面深入了解缺血引发神经元死亡的基本机制，并探讨旨在减轻中风后神经元损失和促进神经恢复的神经保护治疗方法的进展。此外，我们广泛探讨了关于缺血性中风期间神经元死亡潜在途径的公认发现，包括细胞凋亡、自噬、焦亡、铁死亡和坏死之间的相互作用，这些共同影响神经元的命运。我们还讨论了神经保护治疗的进展，包括从药物调节到基于干细胞的疗法等一系列干预措施，旨在减少缺血性中风后的神经元损伤并增强功能恢复。尽管有这些进展，但将机制性见解转化为有效的临床治疗仍面临挑战。虽然神经保护策略在临床前模型中显示出前景，但其在人体试验中的疗效并不一致，这通常是由于缺血性中风的复杂病理和干预时机所致。总之，这篇综述综合了对驱动缺血后神经元死亡的分子和细胞途径复杂相互作用的机制性见解。它揭示了潜在神经保护治疗的前沿进展，强调了再生医学的前景，并对潜在的临床突破提供了前瞻性观点。精准靶向干预措施的不断发展有望显著加强预防策略并改善临床结果。
