17Beta-estradiol activates adenosine A(2a) receptor after subarachnoid hemorrhage
Lin, CL; Dumont, AS; Tsai, YJ; Huang, JH; Chang, KP; Kwan, AL; Hong, YR; Howng, SL
| HERO ID | 6319477 |
|---|---|
| In Press | No |
| Year | 2009 |
| Title | 17Beta-estradiol activates adenosine A(2a) receptor after subarachnoid hemorrhage |
| Authors | Lin, CL; Dumont, AS; Tsai, YJ; Huang, JH; Chang, KP; Kwan, AL; Hong, YR; Howng, SL |
| Journal | Journal of Surgical Research |
| Volume | 157 |
| Issue | 2 |
| Page Numbers | 208-215 |
| Abstract | <strong>BACKGROUND: </strong>Our previous study showed that 17beta-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 SAH-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).<br /><br /><strong>MATERIALS AND METHODS: </strong>The two-hemorrhage SAH 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.<br /><br /><strong>RESULTS: </strong>E2 significantly attenuated vasospasm. Seven days after the first SAH, 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 anti-spastic effects of E2. The expression of Bax did not change in the dentate gyrus after SAH with or without treatment.<br /><br /><strong>CONCLUSIONS: </strong>The down-regulated AR-A(2A) and ERK may play a role in vasospasm and apoptosis after SAH. The beneficial effect of E2 in the attenuating SAH-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 SAH in humans. |
| Doi | 10.1016/j.jss.2008.08.021 |
| Pmid | 19181336 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |