Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Jerusalem, Israel.
Brain Res. 2011 Aug 17;1407:90-6. doi: 10.1016/j.brainres.2011.06.035. Epub 2011 Jun 23.
We characterized the effect of acute ischemic stroke on the activation of the hypothalamic-pituitary-adrenal (HPA) axis and evaluated the role of glucocorticoids (GC) in the clinical outcome following ischemic stroke. Male spontaneous hypertensive rats underwent permanent middle cerebral artery occlusion (PMCAO) and developed a cortical infarct. At 4h post-PMCAO or sham operation, serum levels of ACTH and corticosterone (CS) were elevated 5 and 4 fold respectively as compared to controls and then returned to basal levels at 24h post surgery. In these experimental groups we found also a significant depletion of median eminence (ME)-CRH(41). In adrenalectomized (Adx) rats that underwent PMCAO the degree of motor disability and infarct volume was similar to that of intact rats. Administration of dexamethasone (Dex) to Adx-PMCAO rats significantly improved the motor disability and decreased the infarct volume. However, in sham-Adx with PMCAO, Dex had no effect on these two parameters. In rats with PMCAO or sham-PMCAO, brain production of PGE(2) was significantly increased. This effect was further enhanced in Adx-PMCAO rats and significantly inhibited by Dex. In conclusion, activation of the HPA axis following PMCAO is due to stress induced by surgery. This activation is mediated by hypothalamic CRH(41). Absence of endogenous GC or administration of Dex in naïve rats does not alter motor and pathological parameters in the acute stage following PMCAO. In contrast, administration of Dex significantly improved the outcome following cerebral ischemia in Adx rats which may be due to increased glucocorticoid receptors. Brain production of PGE(2) does not play an important role in the pathophysiology of the acute phase of cerebral ischemia.
我们描述了急性缺血性脑卒中对下丘脑-垂体-肾上腺（HPA）轴激活的影响，并评估了糖皮质激素（GC）在缺血性脑卒中后的临床转归中的作用。雄性自发性高血压大鼠行永久性大脑中动脉闭塞（PMCAO），形成皮质梗死。与对照组相比，PMCAO 或假手术 4 小时后，血清 ACTH 和皮质酮（CS）水平分别升高了 5 倍和 4 倍，术后 24 小时恢复到基础水平。在这些实验组中，我们还发现正中隆起（ME）-CRH（41）明显减少。在接受 PMCAO 的肾上腺切除术（Adx）大鼠中，运动障碍和梗死体积与完整大鼠相似。给予地塞米松（Dex）治疗 Adx-PMCAO 大鼠可显著改善运动障碍并减少梗死体积。然而，在假手术-Adx 伴 PMCAO 中，Dex 对这两个参数没有影响。在 PMCAO 或假手术-PMCAO 大鼠中，脑内 PGE（2）的产生显著增加。这种作用在 Adx-PMCAO 大鼠中进一步增强，并被 Dex 显著抑制。总之，PMCAO 后 HPA 轴的激活是由于手术引起的应激。这种激活是由下丘脑 CRH（41）介导的。在未接受 GC 处理的大鼠中，或在未接受 GC 处理的大鼠中给予 Dex，并不改变 PMCAO 后急性期的运动和病理参数。相反，在 Adx 大鼠中，Dex 的给予显著改善了脑缺血后的转归，这可能是由于糖皮质激素受体的增加。脑内 PGE（2）的产生在脑缺血急性期的病理生理过程中没有重要作用。
