Centre for the Developing Brain, Institute of Reproductive and Developmental Biology, Department of Surgery and Cancer, Imperial College, Hammersmith Campus, London, UK.
Lancet Neurol. 2012 Jun;11(6):556-66. doi: 10.1016/S1474-4422(12)70058-3. Epub 2012 May 16.
Cerebral palsy is caused by injury or developmental disturbances to the immature brain and leads to substantial motor, cognitive, and learning deficits. In addition to developmental disruption associated with the initial insult to the immature brain, injury processes can persist for many months or years. We suggest that these tertiary mechanisms of damage might include persistent inflammation and epigenetic changes. We propose that these processes are implicit in prevention of endogenous repair and regeneration and predispose patients to development of future cognitive dysfunction and sensitisation to further injury. We suggest that treatment of tertiary mechanisms of damage might be possible by various means, including preventing the repressive effects of microglia and astrocyte over-activation, recapitulating developmentally permissive epigenetic conditions, and using cell therapies to stimulate repair and regeneration Recognition of tertiary mechanisms of damage might be the first step in a complex translational task to tailor safe and effective therapies that can be used to treat the already developmentally disrupted brain long after an insult.
脑瘫是由于未成熟大脑的损伤或发育障碍引起的，导致严重的运动、认知和学习缺陷。除了与初始损伤到未成熟大脑相关的发育中断外，损伤过程还可能持续数月或数年。我们认为这些三级损伤机制可能包括持续的炎症和表观遗传变化。我们提出，这些过程隐含在阻止内源性修复和再生的过程中，并使患者易患未来认知功能障碍和对进一步损伤的敏感性。我们建议，通过各种手段治疗三级损伤机制是可能的，包括防止小胶质细胞和星形胶质细胞过度激活的抑制作用、重现发育上允许的表观遗传条件，以及使用细胞疗法刺激修复和再生。对三级损伤机制的认识可能是一项复杂的转化任务的第一步，该任务旨在定制安全有效的治疗方法，以治疗在损伤后很久已经发育障碍的大脑。
