Schäbitz W R, Schwab S, Spranger M, Hacke W
Department of Neurology, University of Heidelberg, Germany.
J Cereb Blood Flow Metab. 1997 May;17(5):500-6. doi: 10.1097/00004647-199705000-00003.
Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 micrograms/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls (P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 +/- 27.1 mm3 in BDNF-treated animals and 139.2 +/- 56.4 mm3 in controls (mean +/- SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 +/- 7.1 mm3 in BDNF-treated animals and 37.9 +/- 19.8 mm3 in controls (mean +/- SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal cerebral ischemia in rats and support the hypothesis of a neuroprotective role for BDNF in stoke.
脑源性神经营养因子（BDNF）通过高亲和力受体酪氨酸激酶（TrkB）发挥作用，广泛分布于整个中枢神经系统，并在体外对包括海马、小脑和皮质神经元在内的多种神经元细胞显示出营养作用。在体内，BDNF可使运动神经元、海马和黑质多巴胺能细胞免受创伤性和中毒性脑损伤。短暂性大脑中动脉闭塞（MCAO）后，皮质神经元中BDNF-mRNA的上调表明BDNF可能在局灶性脑缺血中发挥神经保护作用。在本研究中，在Wistar大鼠（每组n = 13）通过腔内缝合进行永久性大脑中动脉闭塞前24小时开始，将BDNF（2.1微克/天）溶解于赋形剂中或单独给予赋形剂（对照组），经脑室给药8天。两组手术期间记录的生理变量无差异。与对照组相比，BDNF治疗组动物的神经功能缺损（0至4级评分）每日评估结果有所改善（P < 0.05；方差分析和谢费检验）。实验期间，BDNF治疗组动物与对照组的体重无显著差异。在MCAO后第7天选择性处死动物后，对大脑进行2,3,5-三苯基氯化四氮唑染色，以计算梗死体积并进行组织学检查（苏木精和伊红染色以及胶质纤维酸性蛋白染色）。BDNF治疗组动物的平均总梗死体积为83.1±27.1立方毫米，对照组为139.2±56.4立方毫米（平均值±标准差；P < 0.01，非配对双尾t检验）。BDNF治疗组动物的皮质梗死体积为10.8±7.1立方毫米，对照组为37.9±19.8立方毫米（平均值±标准差；P < 0.05；非配对双尾t检验），而尾状核-壳核梗死的缺血性病变体积无显著差异。这些结果表明，脑室注射BDNF预处理可减少大鼠局灶性脑缺血后的梗死面积，并支持BDNF在中风中具有神经保护作用的假说。
