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Dynamic changes of excitatory amino acid receptors in the rat hippocampus following transient cerebral ischemia

机译:短暂性脑缺血后大鼠海马兴奋性氨基酸受体的动态变化

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摘要

The changes in excitatory amino acid receptor ligand binding induced by transient cerebral ischemia were studied in the rat hippocampal subfields. Ten minutes of ischemia was induced by common carotid artery occlusion combined with hypotension, and the animals were allowed variable periods of recovery ranging from 1 day to 4 weeks. The binding of 3H-AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) to quisqualate receptors, 3H-kainic acid (KA) to kainate receptors, and 3H-glutamate to N-methyl-D-aspartate (NMDA) receptors as determined by quantitative autoradiography. One week following ischemia the CA1 region of the hippocampus displayed a severe (90%) dendrosomatic lesion with preservation of presynaptic terminals. This was associated with a 60% decrease in AMPA binding and a 25% decrease in glutamate binding to NMDA receptors. At 4 weeks postischemia, both AMPA and NMDA sites were greatly reduced. Although the dentate gyrus granule cells are resistant to an ischemic insult of this magnitude, this region showed marked changes in receptor binding. One week following ischemia, the AMPA and NMDA binding decreased by approximately 40 and 20%, respectively. Following 2 weeks of recovery, the NMDA binding was not significantly different from control level, while the AMPA binding remained depressed up to 4 weeks postischemia. The high density of KA binding sites in the inner molecular layer of the dentate gyrus was unaffected by the ischemic insult, despite an extensive degeneration of cells in the hilus of dentate gyrus which projects glutamatergic afferents to this area.(ABSTRACT TRUNCATED AT 250 WORDS)
机译:在大鼠海马亚区研究了短暂性脑缺血引起的兴奋性氨基酸受体配体结合的变化。颈总动脉闭塞并伴有低血压,诱发了10分钟的局部缺血,使动物的恢复期从1天到4周不等。 3H-AMPA(α-氨基-3-羟基-5-甲基-4-异恶唑丙酸)与半胱氨酸受体的结合,3H-海藻酸(KA)与海藻酸酯受体的结合以及3H-谷氨酸与N-甲基-D-的结合通过定量放射自显影确定的天冬氨酸(NMDA)受体。缺血后一周,海马CA1区显示出严重的树突状体病变(90%),并保留了突触前末端。这与AMPA结合降低60%,谷氨酸与NMDA受体结合降低25%有关。缺血后4周,AMPA和NMDA位点均大大减少。尽管齿状回颗粒细胞对这种程度的缺血性损伤有抵抗力,但是该区域在受体结合方面显示出明显的变化。缺血后一周,AMPA和NMDA的结合分别下降约40%和20%。恢复2周后,NMDA结合与对照水平无显着差异,而AMPA结合在缺血后最多4周仍保持抑制状态。齿状回的内分子层中的KA结合位点的高密度不受缺血性损伤的影响,尽管在齿状回的孔中大量的细胞变性使谷氨酸能传入该区域(ABSTRACT TRUNCATED AT 250 WORDS)

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