Although cerebral vasospasm following subarachnoid hemorrhage (SAH) has been known for more than half of a century, SAH-induced cerebral vasospasm is still a major cause of mortality and neurological morbidity in patients with ruptured intracranial aneurysm. In spite of the intensive research efforts, SAH-induced vasospasm remains incompletely understood from both pathogenic and therapeutic perspectives. At present, effective preventive and therapeutic strategies are available in clinical practice only. Many pathological processes have been proposed for the pathogenesis of delayed cerebral vasospasm following SAH, such as endothelial damage, smooth muscle contraction, change in vascular responsiveness, and inflammatory and/or immunological response of the vascular wall. Gender differences in the outcome of aneurysmal SAH are controversial, and the potential influence of estradiol on SAH-induced vasospasm and secondary brain injury is emerging as an alternative tactic for managing aneurysm in SAH. Treatment with 17β-estradiol (E2) at different physiological levels prevents experimental SAH-induced cerebral vasospasm in rats. The beneficial effect of E2 may, in part, be related to the prevention of augmentation of inducible nitric oxide synthase (iNOS) expression and the preservation of normal endothelial nitric oxide synthase expression following SAH. This mechanism of inhibition of the SAH-induced increase in iNOS levels occurs by increasing the association of the p65/ER complex, which in turn inhibits the binding of p65 to the iNOS DNA. In addition, E2 also acts at the apoptotic signals including tumor necrosis factor-α, caspase-3, and Bcl-2, and increases the levels of adenosine A2A receptor (AR-A2A), ERK, and phospho-Akt in the dentate gyrus to prevent SAH-induced apoptotic death. The antispastic and antiapoptotic effects of E2 are achieved through estrogen receptor-dependent mechanisms. These data support further investigation of using E2 in the treatment of SAH in humans.
|頁（從 - 到）||325-329|
|期刊||Journal of Experimental and Clinical Medicine(Taiwan)|
|出版狀態||已發佈 - 十二月 2012|
ASJC Scopus subject areas