Pathogenic and Therapeutic Perspectives of 17β-Estradiol in the Treatment of Subarachnoid Hemorrhage-induced Vasospasm and Secondary Brain Injury

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