ISCHEMIC BRAIN EDEMA--EFFECT OF Y-HYDROXYBUTYRATE ON S2-RECEPTOR BINDING SITES

缺血性脑水肿--Y-羟基丁酸对S2-受体结合位点的影响

• 批准号: 3969021
• 负责人: M SPATZ
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3969021
• 关键词: brain edema; cerebral ischemia /hypoxia; cerebrovascular occlusions; chemical binding; gamma hydroxybutyrate; radiotracer; serotonin; serotonin inhibitor

Our previous results demonstrated that the ischemic edema is associated with an increased release of 5-HT and kinetic changes in the properties of synaptosomal serotonin (S-2)-receptor binding sites. In another study we have also shown that either preischemic or postischemic treatment of gerbils with Gamma-hydroxybutyrate (GHB), an endogenous central nervous system depressant, reduces the formation of edema and stabilizes the 5-HT metabolism. To shed some more light on the pathomechanisms of edema formation, we investigated the preischemic GHB effect on S-2-receptor binding sites in the ischemic model of edema on gerbils subjected to 15 min bilateral carotid artery occlusion and release for 1 hr. These studies have shown that GHB given prior to the inducion of bilateral carotid artery occlusion in gerbils prevented the ischemically induced changes in S-2-receptor binding sites using 3H-ketanserin as ligand (which labels specifically S-2-receptor sites). Thus, the capability of GHB to reduce the formation of ischemic edema and stablize the 5-HT metabolism (observed in previous studies), as well as to prevent ischemic changes in the kinetic properties of S-2-receptor binding sites, reinforces the contention of GHB effect of 5-HT metabolic pathway.

我们先前的研究结果表明，缺血性水肿与 随着5-羟色胺释放的增加和药物性质的动力学变化 突触体5-羟色胺(S-2)受体结合部位。在另一项研究中，我们 还表明，无论是缺血前还是缺血后治疗， 内源性中枢神经--羟丁酸(GHb)沙土鼠 系统抑制剂，减少水肿的形成，稳定5-羟色胺 新陈代谢。更多地阐明水肿病的发病机制 形成，我们研究了缺血前羟丁酸对S-2受体的影响 15min沙土鼠脑缺血模型中结合部位的研究 结扎双侧颈总动脉，松解1小时。 这些研究表明，在给予GHb之前，对双侧的诱导 沙土鼠颈动脉阻断对缺血性脑缺血的预防作用 以~3H-酮丝氨酸为配体的S-2受体结合部位的变化 具体标记S-2-受体位点)。因此，GHB的能力可以 减少缺血性水肿的形成，稳定5-羟色胺代谢 (在以前的研究中观察到)，以及防止脑缺血改变 S-2受体结合位点的动力学性质，加强了 5-羟色胺代谢途径中GHB效应的争论。