Intraventricular brain-derived neurotrophic factor reduces infarct size after focal cerebral ischemia in rats

被引:326
作者
Schabitz, WR [1 ]
Schwab, S [1 ]
Spranger, M [1 ]
Hacke, W [1 ]
机构
[1] UNIV HEIDELBERG, DEPT NEUROL, D-69120 HEIDELBERG, GERMANY
关键词
brain-derived neurotrophic factor; neurotrophins; focal cerebral ischemia; MCAO; histology;
D O I
10.1097/00004647-199705000-00003
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu g/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 mm(3) in BDNF-treated animals and 139.2 +/- 56.4 mm(3) in controls (mean +/- SD; P < 0.01, unpaired, two-tailed t-test), The cortical infarct volume was 10.8 +/- 7.1 mm(3) in BDNF-treated animals and 37.9 +/- 19.8 mm(3) 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.
引用
收藏
页码:500 / 506
页数:7
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