17β-Estradiol Activates Adenosine A2a Receptor After Subarachnoid Hemorrhage

Background. Our previous study showed that 17 beta-estradiol (E2) and an adenosine A(2A) receptor (AR-A(2A)) agonist could attenuate subarachnoid hemorrhage (SAH)-induced cerebral vasospasm via preventing the augmentation of iNOS expression and preserving the normal eNOS expression. This study tests the hypothesis that E2 attenuates SAN-induced vasospasm and apoptosis by activating adenosine AR-A(2A) and extracellular signal-regulated kinase 1 and 2 (ERK1/2), and by altering antiapoptotic and proapoptotic protein expression (Bcl-2 and Bax, respectively). Materials and methods. The two-hemorrhage SAN model in rat was used. Animals were treated with E2 with or without a nonselective estrogen receptor (ER) antagonist (ICI182,780). The cross sectional areas of the basilar artery and terminal dUTP nick-end labeling (TUNEL) were used to determine the degree of vasospasm and apoptosis, respectively. The expressions of Bcl-2, Bax, AR-A(2A), and ERK1/2 in the cerebral cortex, hippocampus, and dentate gyrus were investigated. Results. E2 significantly attenuated vasospasm. Seven days after the first SAN, TUNEL scores were significantly increased, and protein levels of AR-A(2A), ERK1/2, and Bcl-2 were significantly decreased in the dentate gyrus only but not in the cortex and hippocampus. These changes were reversed by E2 while ICI182,780 abrogated the antiapoptotic and antispastic effects of E2. The expression of Bax did not change in the dentate gyrus after SAN with or without treatment. Conclusions. The down-regulated AR-A(2A) and ERK may play a role in vasospasm and apoptosis after SAN. The beneficial effect of E2 in the attenuating SAN-induced vasospasm and apoptosis may be due to an increased expression of AR-A(2A) and ERK via ER-dependent mechanisms. These data may support further investigation of E2 in the treatment of SAN in humans. (C) 2009 Elsevier Inc. All rights reserved.