Osteogenic protein-1 protects against cerebral infarction induced by MCA ligation in adult rats
Osteogenic protein-1 protects against cerebral infarction induced by MCA ligation in adult rats
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DOI：
10.1161/01.str.30.1.126
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发表时间：
1999-01-01
期刊：
影响因子：
8.3
通讯作者：
Wang, Y
中科院分区：
文献类型：
--
作者：
Lin, SZ;Hoffer, BJ;Wang, Y
背景与目的：成骨蛋白-1(Ostegen Protein-1，OP1)不仅对骨组织具有营养作用，而且在体外也影响神经元的存活和分化。OP1的特异性受体存在于大脑和脊髓中，在脑挫伤时可以上调。OP1是转化生长因子-β超家族成员之一，其中几个成员具有神经保护活性。本研究观察了OP1对成年动物脑缺血的保护作用。方法成年雄性SD大鼠用水合氯醛麻醉。给大鼠皮质或侧脑室注射OP1或Vehicle。分别于注射OP1后30分钟、24小时或72小时结扎右侧大脑中动脉(MCA)90分钟。再灌注24小时后，对动物进行运动行为测试。这些动物随后被乌拉坦麻醉，并在心脏内灌流生理盐水。取脑组织，切片，与2%三苯基四氮唑氯化铵孵育，以定位梗塞区域。结果：仅在大脑中动脉结扎前24小时给予OP1预处理的动物显示运动障碍减轻。OP1在MCA结扎前30分钟或72小时给药，并不能减少皮质梗塞。相反，在MCA结扎前24小时给予OP1可显著减少大脑皮质的梗塞体积，这与行为学结果一致。结论：在MCA结扎前24小时脑内注射OP1可减少大脑皮层的缺血损伤。
Background and Purpose-Osteogenic protein-1 (OP1) not only possesses trophic activity on bone tissue but also influences neuronal survival and differentiation in vitro. Specific receptors for OP1 are present in brain and spinal cord and can be upregulated during cerebral contusion. OP1 is a member of the transforming growth factor-p superfamily, several of whose members possess neuroprotective activity. In this study, the neuroprotective effect of OP1 in cerebral ischemia was evaluated in adult animals.Methods-Adult male Sprague-Dawley rats were anesthetized with chloral hydrate. OP1 or vehicle was administered intracortically or intracerebroventricularly to the rats. Thirty minutes, 24 hours, or 72 hours after OP1 injection, the right middle cerebral artery (MCA) was ligated for 90 minutes. Twenty-four hours after reperfusion, animals were tested for motor behavior. The animals were subsequently anesthetized with urethane and perfused intracardially with saline. Brain tissue was removed, sliced, and incubated with 2% triphenyltetrazolium chloride to localize the area of infarction.Results-Only animals pretreated with OP1 24 hours before MCA ligation showed a reduction in motor impairment. OP1, given 30 minutes or 72 hours before MCA ligation, did not reduce cortical infarction. In contrast, pretreatment with OP1 24 hours before MCA ligation significantly attenuated the volume of infarction in the cortex, in agreement with the behavioral findings.Conclusions-Intracerebral administration of OP1 24 hours before MCA ligation reduces ischemia-induced injury in the cerebral cortex.