Schäbitz Wolf-Rüdiger, Steigleder Tobias, Cooper-Kuhn Christiana M, Schwab Stefan, Sommer Clemens, Schneider Armin, Kuhn H Georg
Department of Neurology, University of Münster, Germany.
Stroke. 2007 Jul;38(7):2165-72. doi: 10.1161/STROKEAHA.106.477331. Epub 2007 May 17.
The discovery of spontaneous neuronal replacement in the adult brain has shifted experimental stroke therapies toward a combined approach of preventing neuronal cell death and inducing neuronal plasticity. Brain-derived neurotrophic factor (BDNF) was shown to induce antiapoptotic mechanisms after stroke and to reduce infarct size and secondary neuronal cell death. Moreover, in intact animals, BDNF is a potent stimulator of adult neurogenesis.
The current study analyzed the effects of BDNF on induction of neuronal progenitor cell migration and sensorimotor recovery after cortical photothrombotic stroke.
Daily intravenous bolus applications of BDNF during the first 5 days after stroke resulted in significantly improved sensorimotor scores up to 6 weeks. At the structural level, BDNF significantly increased neurogenesis in the dentate gyrus and enhanced migration of subventricular zone progenitor cells to the nearby striatum of the ischemic hemisphere. BDNF treatment could not, however, further stimulate progenitor cell recruitment to the cortex.
These findings consolidate the role of BDNF as a modulator of neurogenesis in the brain and as an enhancer of long-term functional neurological outcome after cerebral ischemia.
成体大脑中自发神经元替代现象的发现，使实验性中风治疗转向预防神经元细胞死亡和诱导神经元可塑性的联合方法。脑源性神经营养因子（BDNF）已被证明在中风后可诱导抗凋亡机制，并减小梗死灶大小和继发性神经元细胞死亡。此外，在完整动物中，BDNF是成年神经发生的有力刺激因子。
本研究分析了BDNF对皮质光血栓形成性中风后神经元祖细胞迁移诱导及感觉运动恢复的影响。
中风后前5天每日静脉推注BDNF，可使感觉运动评分在长达6周的时间内显著改善。在结构水平上，BDNF显著增加齿状回中的神经发生，并增强脑室下区祖细胞向缺血半球附近纹状体的迁移。然而，BDNF治疗不能进一步刺激祖细胞向皮质募集。
这些发现巩固了BDNF作为大脑神经发生调节因子以及脑缺血后长期功能性神经学结果增强剂的作用。
