Fried R L, Nowak T S
Stroke. 1987 Jul-Aug;18(4):765-70. doi: 10.1161/01.str.18.4.765.
Peptides derived from each of the 3 endogenous opioid precursors were measured in gerbil brain regions at various times after transient bilateral carotid artery occlusion using radioimmunoassays specific for beta-endorphin-, met-enkephalin-, and dynorphin A-related peptides. Lasting changes were observed only in the hippocampus. The most striking effect was on dynorphin A immunoreactivity, which was reduced by 30-40% as early as 1 hour after recirculation and remained at 50% of the control level for at least 1 week. In some experiments dynorphin levels showed a transient recovery at 24 hours. These results demonstrate a unique sensitivity of the dynorphin-containing dentate granule cell-mossy fiber pathway to transient ischemia. Although these cells remain histologically intact, the decrease in dynorphin level precedes and continues during the delayed loss of hippocampal CA1 neurons characteristic of this model and further defines the selective vulnerability of hippocampal circuitry following ischemia. These observations clearly identify the hippocampus as a well-defined brain region in which further studies of the postischemic pathophysiology of endogenous opioid peptides may provide a rational basis for evaluating the place of opiate pharmacology in stroke treatment.
使用针对β-内啡肽、甲硫氨酸脑啡肽和强啡肽A相关肽的放射免疫分析法，在短暂双侧颈动脉闭塞后的不同时间，对沙鼠脑区中源自3种内源性阿片肽前体的肽进行了测量。仅在海马体中观察到了持久的变化。最显著的影响是对强啡肽A免疫反应性的影响，再灌注后1小时内，其免疫反应性就降低了30%-40%，并且在至少1周内一直维持在对照水平的50%。在一些实验中，强啡肽水平在24小时时出现短暂恢复。这些结果表明，含有强啡肽的齿状颗粒细胞-苔藓纤维通路对短暂性缺血具有独特的敏感性。尽管这些细胞在组织学上保持完整，但强啡肽水平的降低在该模型特有的海马CA1神经元延迟丢失之前就已出现，并在其过程中持续存在，进一步明确了缺血后海马回路的选择性易损性。这些观察结果清楚地表明，海马体是一个明确的脑区，对内源性阿片肽缺血后病理生理学的进一步研究可能为评估阿片类药物药理学在中风治疗中的地位提供合理依据。
