Neuroprotection With Intraventricular Brain-Derived Neurotrophic Factor in Rat Venous Occlusion Model
Neuroprotection With Intraventricular Brain-Derived Neurotrophic Factor in Rat Venous Occlusion Model
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DOI：
10.1227/neu.0b013e31820c048e
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发表时间：
2011-05-01
期刊：
影响因子：
4.8
通讯作者：
Nakase, Hiroyuki
中科院分区：
文献类型：
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作者：
Takeshima, Yasuhiro;Nakamura, Mitsutoshi;Nakase, Hiroyuki
背景技术背景：随着老年患者神经外科手术数量的增加和颅底神经外科的发展，对可能发生在神经外科环境中的脑静脉损伤的兴趣增加。脑源性神经营养因子（Brain-derived neurotrophic factor，BDNF）可能对脑静脉缺血具有神经保护作用目的：观察脑室内注射BDNF对大鼠脑静脉缺血性脑损伤的梗死面积、细胞凋亡和局部脑血流量（regional cerebral blood flow，rCBF）的影响。每组再随机分为术后2天和7天组。BDNF（2.1 μ g/天）或载体通过脑室内输注泵连续输送。然后光化学封闭两个相邻的对侧皮质静脉。在闭塞后2天和7天，我们组织学测量梗死体积与对侧半球体积的比率，并计数（2天组）半暗带中末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记（TUNEL）阳性凋亡细胞。结果：静脉阻断后第2天，BDNF治疗组大鼠的平均梗死体积明显小于对照组（1.49 +/- 1.44% vs 3.66 +/- 1.51%; P < .05）和7天（0.93 +/- 0.47% vs 1.69 +/- 0.58%; P < .05）。在闭塞后两天，BDNF治疗组大鼠的TUNEL阳性凋亡细胞（17.0 +/- 15.1）明显少于对照组（39.0 +/- 19.6; P <0.05）。结论：脑室内持续给予BDNF可保护脑皮层细胞凋亡，减少梗死面积，而不影响rCBF。
BACKGROUND: The increasing number of neurosurgical procedures for elderly patients and the development of skull base neurosurgery have increased interest in cerebral venous injury that might occur in a neurosurgical setting. Brain-derived neurotrophic factor (BDNF) may have neuroprotective effects against cerebral venous ischemia.OBJECTIVE: To investigate the intraventricular effects of BDNF infusion on infarct size, suppression of apoptosis, and regional cerebral blood flow (rCBF) in cerebral venous ischemic lesions in a rat 2-vein occlusion model.METHODS: Thirty-three male Wistar rats were randomly divided into BDNF-treated and vehicle control groups; each group was further randomly divided into 2-day and 7-day postocclusion groups. BDNF (2.1 mu g/day) or vehicle was delivered continuously via intraventricular infusion pumps. Two adjacent contralateral cortical veins were then photochemically occluded. Two and 7 days after occlusion, we histologically measured ratios of infarct volume to contralateral hemisphere volume and counted (2-day group) terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic cells in the penumbra. rCBF was measured via full-field laser perfusion imaging.RESULTS: The mean infarct volume after venous occlusion was significantly smaller in BDNF-treated rats than in controls at 2 days (1.49 +/- 1.44% vs 3.66 +/- 1.51%; P < .05) and 7 days (0.93 +/- 0.47% vs 1.69 +/- 0.58%; P < .05). Two days after occlusion, there were significantly fewer TUNEL-positive apoptotic cells in the BDNF-treated rats (17.0 +/- 15.1) than in the controls (39.0 +/- 19.6; P < .05). There were no differences in rCBF.CONCLUSION: After 2-vein occlusion, continuous intraventricular administration of BDNF protected the cerebral cortex against apoptosis and reduced infarct size without affecting rCBF.