Neuroprotective effect of aspirin by inhibition of glutamate release after permanent focal cerebral ischaemia in rats
Neuroprotective effect of aspirin by inhibition of glutamate release after permanent focal cerebral ischaemia in rats
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DOI：
10.1046/j.1471-4159.2001.00600.x
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发表时间：
2001-10-01
影响因子：
4.7
通讯作者：
Lizasoain, I
中科院分区：
文献类型：
--
作者：
De Cristóbal, J;Moro, MA;Lizasoain, I
阿司匹林可缩小缺血性中风后的梗塞面积。虽然这一事实被归因于它的抗血小板作用，但也有直接的神经保护作用的报道。我们最近已经证明，阿司匹林通过增加ATP的产生，在‘体外’脑缺血模型中抑制谷氨酸的释放，从而起到神经保护作用。本研究旨在确定阿司匹林对谷氨酸释放的抑制是否对永久性局灶性脑缺血的全动物模型具有保护作用。成年Fischer大鼠结扎颈总动脉和大脑中动脉，造成局灶性脑缺血。阻断后每隔一定时间测定中枢谷氨酸和血清谷氨酸水平。然后处死动物，测量脑梗塞体积。阿司匹林(30 mg/kg ip.缺血前2小时给予阿司匹林)可显著缩小脑梗塞体积，这种作用与阿司匹林抑制脑缺血引起的脑缺血和缺血后血清谷氨酸浓度升高有关。阿司匹林还能抑制脑缺血引起的脑组织ATP水平的下降。我们目前的发现表明，阿司匹林的神经保护作用有一种新的机制，这种作用发生在抗聚集止痛药的浓度范围内，适用于有缺血事件风险的患者。
Aspirin reduces the size of infarcts after ischaemic stroke. Although this fact has been attributed to its anti-platelet actions, direct neuroprotective effects have also been reported. We have recently demonstrated that aspirin is neuroprotective by inhibiting glutamate release in 'in vitro' models of brain ischaemia, via an increase in ATP production. The present study was designed to determine whether the inhibition of glutamate release induced by aspirin might be protective in a whole-animal model of permanent focal brain ischaemia. Focal brain ischaemia was produced in mate adult Fischer rats by occluding both the common carotid and middle cerebral arteries. Central and serum glutamate levels were determined at fixed intervals after occlusion. The animals were then killed and infarct volume was measured. Aspirin (30 mg/kg i.p. administered 2 h before the occlusion) produced a significant reduction in infarct volume, an effect that correlated with the inhibition caused by aspirin on ischaemia-induced increase in brain and serum glutamate concentrations after the onset of the ischaemia. Aspirin also inhibited ischaemia-induced decrease in brain ATP levels. Our present findings show a novel mechanism for the neuroprotective effects of aspirin, which takes place at concentrations In the anti-aggregant-analgesic range, useful in the management of patients with risk of ischaemic events.