Mechanisms of development of ischemic neuronal cell death and protection against ischemic neuronal cell death.

采用沙土鼠双侧颈总动脉短暂性阻断，造成海马CA 1区锥体神经元选择性迟发性变性，并通过原代培养，探讨缺血性神经元死亡的发生机制及对缺血性神经元死亡的保护。NMDA受体拮抗剂MK-801和一氧化氮合酶抑制剂L-NAME可减轻这种选择性损伤。腺苷A_1受体拮抗剂CHA和腺苷A_2受体拮抗剂CGS-21680也能有效地保护原代培养的CA_1区锥体神经元，使细胞在缺氧缺糖条件下死亡。这种细胞死亡通过MK-801、L-NAME、腺苷、CHA和CGS-21680处理而减弱。CHA可降低缺氧/低血糖引起的细胞内Ca ~（2+）水平升高。CGS-20680的神经保护作用可被蛋白激酶A抑制剂H-89所减弱，提示腺苷是一种内源性神经保护物质，可对抗缺血性神经细胞死亡。此外，这一结果增加了腺苷成为治疗血管损伤所致痴呆的药物的可能性。

Mechanisms of development of ischemic neuronal cell death and protection against ischemic neuronal cell death were examined by using ischemic animal model and primary culture.Transient bilateral carotid occlusion in gerbil caused a selective delayed degeneration of the pyramidal neurons in the CA1 hippocampal area. This selective damage was attenuated by MK-801, a NMDA receptor antagonist and L-NAME, a nitric oxide synthase inhibitor. Moreover, CHA, an adenosine A1 receptor antagonist and CGS-21680, an adenosine A2 receptor antagonist, were also effective in protection of CA1 pyramidal neurons.The neuronal cell death caused, when the primary culture cell was incubated in hypoxia and hypoglycemia solution. This cell death was attenuated by treatment of MK-801, L-NAME, adenosine, CHA and CGS-21680. CHA reduced hypoxia/hypoglycemia-induced elevation of intracellular Ca2+ level. Neuroprotective effects of CGS-20680 was attenuated by H-89, a protein kinase A inhibitor.These results indicate that adenosine is endogenous neuroprotection substance against ischemic neuronal cell death. Moreover, this results rise the possibility that adenosine becomes a drug for the dementia induced by vascular damage.