Dementia and Ageing Disorders, Department of Neurology, University Hospital Essen, Hufelandstr 55, D-45122 Essen, Germany.
Brain. 2011 Jan;134(Pt 1):84-99. doi: 10.1093/brain/awq344.
The promotion of post-ischaemic motor recovery remains a major challenge in clinical neurology. Recently, plasticity-promoting effects have been described for the growth factor erythropoietin in animal models of neurodegenerative diseases. To elucidate erythropoietin's effects in the post-acute ischaemic brain, we examined how this growth factor influences functional neurological recovery, perilesional tissue remodelling and axonal sprouting of the corticorubral and corticobulbar tracts, when administered intra-cerebroventricularly starting 3 days after 30 min of middle cerebral artery occlusion. Erythropoietin administered at 10 IU/day (but not at 1 IU/day), increased grip strength of the contralesional paretic forelimb and improved motor coordination without influencing spontaneous locomotor activity and exploration behaviour. Neurological recovery by erythropoietin was associated with structural remodelling of ischaemic brain tissue, reflected by enhanced neuronal survival, increased angiogenesis and decreased reactive astrogliosis that resulted in reduced scar formation. Enhanced axonal sprouting from the ipsilesional pyramidal tract into the brainstem was observed in vehicle-treated ischaemic compared with non-ischaemic animals, as shown by injection of dextran amines into both motor cortices. Despite successful remodelling of the perilesional tissue, erythropoietin enhanced axonal sprouting of the contralesional, but not ipsilesional pyramidal tract at the level of the red and facial nuclei. Moreover, molecular biological and histochemical studies revealed broad anti-inflammatory effects of erythropoietin in both hemispheres together with expression changes of plasticity-related molecules that facilitated contralesional axonal growth. Our study establishes a plasticity-promoting effect of erythropoietin after stroke, indicating that erythropoietin acts via recruitment of contralesional rather than of ipsilesional pyramidal tract projections.
促进缺血后运动功能恢复仍然是临床神经病学的一个主要挑战。最近，在神经退行性疾病的动物模型中，描述了生长因子促红细胞生成素的促可塑性作用。为了阐明促红细胞生成素在急性缺血后大脑中的作用，我们研究了这种生长因子如何影响皮质脊髓束和皮质延髓束的功能神经恢复、病灶周围组织重塑和轴突发芽，当在 30 分钟大脑中动脉闭塞后 3 天开始经脑室给予时。每天 10 IU（但不是 1 IU）的促红细胞生成素给药增加了对侧瘫痪前肢的握力，改善了运动协调能力，而不影响自发运动活动和探索行为。促红细胞生成素的神经恢复与缺血脑组织的结构重塑有关，这反映在神经元存活增加、血管生成增加和反应性星形胶质细胞减少导致疤痕形成减少。与非缺血动物相比，在缺血动物中观察到来自同侧锥体束的轴突向脑干的发芽增强，这是通过将葡聚糖胺注入两个运动皮层来实现的。尽管病灶周围组织的重塑成功，但促红细胞生成素增强了对侧而不是同侧锥体束在红核和面神经核水平的轴突发芽。此外，分子生物学和组织化学研究表明，促红细胞生成素在两个半球都具有广泛的抗炎作用，同时表达与可塑性相关的分子发生变化，促进了对侧轴突生长。我们的研究确立了促红细胞生成素在中风后的促可塑性作用，表明促红细胞生成素通过募集对侧而不是同侧锥体束投射起作用。
