Nellgård B, Gustafson I, Wieloch T
Laboratory for Experimental Brain Research, Lund University Hospital, Sweden.
Anesthesiology. 1991 Aug;75(2):279-287. doi: 10.1097/00000542-199108000-00016.
Glutamate is an important factor in the mechanisms of neuronal damage following cerebral ischemia. Blockade of one type of glutamate receptor, the N-methyl-D-aspartate (NMDA) receptor, decreases brain infarct size in experimental models of permanent focal ischemia, but protection in models of transient reversible ischemia is ambiguous. We investigated the effect of the noncompetitive NMDA receptor antagonist dizocipiline (MK-801) on neuronal damage in the CA1 region of the rat hippocampus, using two models of reversible cerebral ischemia: 10 or 15 min of bilateral common carotid occlusion combined with hypotension, or 6-8.5 min of cardiac arrest. Histopathologic evaluation of neuronal damage was performed 7 days after the ischemic insults. Thirteen groups of rats (a total of 129 animals) were treated with saline or dizocilpine in single or multiple doses ranging from 0.1 to 5 mg.kg-1, given intravenously or intraperitoneally prior to and/or after the ischemic insult. In none of the dizocilpine-treated groups could neuronal protection be demonstrated in the CA1 region of the septal as well as dorsotemporal hippocampus, compared to a corresponding saline-treated group. We conclude that systemically administered noncompetitive NMDA receptor antagonists do not provide a marked protection against neuronal damage after a transient period of severe forebrain ischemia.
谷氨酸是脑缺血后神经元损伤机制中的一个重要因素。在永久性局灶性缺血实验模型中，阻断一种谷氨酸受体，即N-甲基-D-天冬氨酸（NMDA）受体，可减小脑梗死面积，但在短暂性可逆性缺血模型中的保护作用尚不明确。我们使用两种可逆性脑缺血模型，研究了非竞争性NMDA受体拮抗剂地佐环平（MK-801）对大鼠海马CA1区神经元损伤的影响：双侧颈总动脉闭塞合并低血压10或15分钟，或心脏骤停6 - 8.5分钟。缺血损伤7天后对神经元损伤进行组织病理学评估。13组大鼠（共129只动物）在缺血损伤之前和/或之后，静脉内或腹腔内给予单剂量或多剂量范围为0.1至5mg·kg-1的生理盐水或地佐环平。与相应的生理盐水处理组相比，在任何地佐环平处理组中，均未在隔区以及背颞侧海马的CA1区显示出神经元保护作用。我们得出结论，全身给予非竞争性NMDA受体拮抗剂不能为严重前脑缺血短暂期后的神经元损伤提供显著保护。
