Endothelial nitric oxide synthase mediates the cerebrovascular effects of erythropoietin in traumatic brain injury.

Endothelial nitric oxide synthase mediates the cerebrovascular effects of erythropoietin in traumatic brain injury.
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DOI:
10.3389/fimmu.2014.00494
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发表时间:
2014
影响因子:
7.3
通讯作者:
Robertson CS
Robertson CS
中科院分区:
医学2区
文献类型:
--
作者:
Cruz Navarro J;Pillai S;Ponce LL;Van M;Goodman JC;Robertson CS

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背景:促红细胞生成素 (Epo) 可改善创伤后脑血流量 (CBF)、压力自动调节和血管对 L-精氨酸的反应性。本研究探讨了 Epo 对内皮一氧化氮合酶 (eNOS) 产生的一氧化氮的脑血流动力学影响的依赖性。方法:使用激光多普勒血流成像,对野生型 (WT) 和 eNOS 缺陷小鼠的 CBF 进行监测,这些小鼠经历受控的皮质冲击,然后施用 Epo (5000 U/kg) 或生理盐水。结果:受伤后所有组的脑血流量均减少,其中最大的减少发生在撞击部位。 Epo 给药导致 WT 小鼠挫伤周围部位的 CBF 显着升高 [Epo 治疗组为 70.2±3.35%,而生理盐水治疗组为基线的 53±3.3% (p<0.0001)],但 eNOS 缺陷小鼠中没有观察到任何影响。在核心撞击点未发现 CBF 差异,所有组的 CBF 均降至基线的 20-25%。结论:eNOS 缺陷小鼠和 WT 小鼠之间的这些差异表明,Epo 介导的创伤性脑损伤中 CBF 的改善是 eNOS 依赖性的。
Background: Erythropoietin (Epo) improves post-traumatic cerebral blood flow (CBF), pressure autoregulation, and vascular reactivity to l-arginine. This study examines the dependence of these cerebral hemodynamic effects of Epo on nitric oxide generated by endothelial nitric oxide synthase (eNOS). Methods: Using laser Doppler flow imaging, CBF was monitored in wild-type (WT) and eNOS-deficient mice undergoing controlled cortical impact followed by administration of Epo (5000 U/kg) or normal saline. Results: Cerebral blood flow decreased in all groups post-injury with the greatest reductions occurring at the impact site. Epo administration resulted in significantly higher CBF in the peri-contusional sites in the WT mice [70.2 ± 3.35% in Epo-treated compared to 53 ± 3.3% of baseline in saline-treated mice (p < 0.0001)], but no effect was seen in the eNOS-deficient mice. No CBF differences were found at the core impact site where CBF dropped to 20–25% of baseline in all groups. Conclusion: These differences between eNOS-deficient and WT mice indicate that the Epo mediated improvement in CBF in traumatic brain injury is eNOS dependent.
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