Potential role of JAK2 in cerebral vasospasm after experimental subarachnoid hemorrhage.

The Janus kinase (JAK) proteins are key regulators for transducing signals from the cell surface to the nucleus in response to cytokines to orchestrate the appropriate cellular response. Previous studies have demonstrated that JAK1 is activated in the basilar artery after subarachnoid hemorrhage (SAH), however it has not been investigated whether, and to what degree, JAK2 is induced by SAH and also the role of JAK2 in the pathogenesis of cerebral vasospasm following SAH remains unknown. Experiment 1 aimed to investigate the time-course of the JAK2 activation in the basilar artery after SAH. In Experiment 2, we chose the maximum time point of JAK2 activation and assessed the effect of AG490 (a specific JAK2 inhibitor) on regulation of cerebral vasospasm and endothelial apoptosis. All SAH animals were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2. As a result, the elevated expression of activated JAK2 was detected in the basilar artery after SAH and peaked on day 3. After AG490 intracisternal administration, the vasospasm was markedly aggravated and the apoptosis index of endothelial cells was also significantly increased in the basilar arteries. Anti-apoptotic genes such as bcl-2 and bcl-xL were down-regulated after the injections of AG490. Our results suggest that JAK2 is activated in the arterial wall after SAH, playing a beneficial role to vasospasm development, possibly through protecting endothelial cells and up-regulating anti-apoptotic genes.