Neuroprotective effects of MK-801 in different rat stroke models for permanent middle cerebral artery occlusion - Adverse effects of hypothalamic damage and strategies for its avoidance
Neuroprotective effects of MK-801 in different rat stroke models for permanent middle cerebral artery occlusion - Adverse effects of hypothalamic damage and strategies for its avoidance
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DOI：
10.1161/01.str.0000087171.34637.a9
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发表时间：
2003-09-01
期刊：
影响因子：
8.3
通讯作者：
Fisher, M
中科院分区：
文献类型：
--
作者：
Gerriets, T;Stolz, E;Fisher, M
背景和目的-使用缝线技术的永久性大脑中动脉闭塞(MCAO)会导致下丘脑损伤并随后发生高温，这可能会扰乱神经保护药物的研究。本研究比较了地佐西平(MK-801)对不同永久性MCAO模型的神经保护作用。方法60只SD大鼠在MCAO前15分钟开始给予MK-801或安慰剂治疗，分为3组：线栓组(I组)、无下丘脑损伤的大球MCAO组(II组)、大球MCAO伴下丘脑梗塞(III组)。分别于3、6、24小时测量体温。2，3，5-三苯基四氮唑氯化物染色。结果：I组动物存在下丘脑损伤，而III组动物采用改良的大球体MCAO技术故意造成下丘脑损伤。两组动物MCAO后3、6、24小时体温均显著升高。限制大球数可有效避免下丘脑损伤及随后的体温过高(II组)。MK-801在II组有非常显著的神经保护作用，而在I组和III组无显著作用。结论MK-801的下丘脑损伤和随后的高温掩盖了MK-801的神经保护作用。这种副作用可以通过在有限数量的球体上使用大球体MCAO技术来避免。因此，该模型可能比线栓法更适合于研究神经保护药物在永久性局灶性脑缺血中的作用。
Background and Purpose-Permanent middle cerebral artery occlusion (MCAO) with the use of the suture technique causes hypothalamic damage with subsequent hyperthermia, which can confound neuroprotective drug studies. In the present study the neuroprotective effects of dizocilpine (MK-801) were compared in different permanent MCAO models with and without hypothalamic damage and hyperthermia.Methods-Sixty Sprague-Dawley rats were treated with MK-801 or placebo, beginning 15 minutes before MCAO, and assigned to the following groups: suture MCAO (group I), macrosphere MCAO without hypothalamic damage (group II), or macrosphere MCAO with intentionally induced hypothalamic infarction (group III). Body temperature was measured at 3, 6, and 24 hours. Lesion size was determined after 24 hours ( 2,3,5-triphenyltetrazolium chloride staining).Results-Hypothalamic damage was present in animals in group I and was intentionally induced in group III with the use of a modified macrosphere MCAO technique. Body temperature was significantly increased 3, 6, and 24 hours after MCAO in these 2 groups of animals. Hypothalamic damage and subsequent hyperthermia could be avoided effectively by limiting the number of macrospheres (group II). MK-801 provided a highly significant neuroprotective effect in group II but not in groups I and III.Conclusions-Hypothalamic damage with subsequent hyperthermia masked the neuroprotective effect of MK-801. This side effect can be avoided by using the macrosphere MCAO technique with a limited number of spheres. This model therefore may be more appropriate to study the effects of neuroprotective drugs in permanent focal cerebral ischemia than the suture method.