A potential role for erythropoietin in focal permanent cerebral ischemia in mice
A potential role for erythropoietin in focal permanent cerebral ischemia in mice
复制标题
DOI：
10.1097/00004647-199906000-00007
复制
发表时间：
1999-06-01
影响因子：
6.3
通讯作者：
Petit, E
中科院分区：
文献类型：
--
作者：
Bernaudin, M;Marti, HH;Petit, E
本研究首次描述了促红细胞生成素 (Epo) 和 Epo 受体 (Epo-R) 的时间和空间细胞表达与小鼠局灶性永久性缺血后脑梗塞的演变。除了神经元和星形胶质细胞中 Epo 的基础表达外，缺血后 Epo 表达还特异地定位于内皮细胞（1 天）、小胶质细胞/巨噬细胞样细胞（3 天）和反应性星形胶质细胞（闭塞后 7 天）。在这些条件下，对于每种细胞类型，Epo-R 表达始终先于 Epo 表达。这些结果支持这样的假设：在局灶性脑梗塞的活跃演变过程中，Epo及其相应受体不断形成，并且Epo/Epo-R系统可能参与缺血后的神经保护和重组过程（例如血管生成和神经胶质增生）。为了支持这一假设，在诱导脑缺血前 24 小时，用重组 Epo 治疗的小鼠发现梗塞体积显着减少（47%；P < 0.0002）。基于上述，我们提出Epo/Epo-R系统是一种内源性机制，可以保护大脑免受血流减少造成的损伤，这种机制可以通过脑室内应用外源性重组Epo来放大。
The present study describes, for the first time, a temporal and spatial cellular expression of erythropoietin (Epo) and Epo receptor (Epo-R) with the evolution of a cerebral infarct after focal permanent ischemia in mice. In addition to a basal expression of Epo in neurons and astrocytes, a postischemic Epo expression has been localized specifically to endothelial cells (1 day), microglia/macrophage-like cells (3 days), and reactive astrocytes (7 days after occlusion). Under these conditions, the Epo-R expression always precedes that of Epo for each cell type. These results support the hypothesis that there is a continuous formation of Epo, with its corresponding receptor, during the active evolution of a focal cerebral infarct and that the Epo/Epo-R system might be implicated in the processes of neuroprotection and restructuring (such as angiogenesis and gliosis) after ischemia. To support this hypothesis, a significant reduction in infarct volume (47%; P < 0.0002) was found in mice treated with recombinant Epo 24 hours before induction of cerebral ischemia. Based on the above, we propose that the Epo/Epo-R system is an endogenous mechanism that protects the brain against damages consequent to a reduction in blood flow, a mechanism that can be amplified by the intracerebroventricular application of exogenous recombinant Epo.