Background and Purpose
We have previously investigated several signaling pathways of cerebral vasospasm after subarachnoid hemorrhage (SAH). This study explored a pivotal role of c-Jun N-terminal kinase (JNK) in inflammation and cerebral vasospasm.
Method
Twenty-seven dogs were randomly assigned to 5 groups: control, SAH without treatment, SAH+dimethyl sulfoxide (DMSO), SAH+JNK inhibitor SP600125 (10 μmol/L), and SAH+SP600125 (30 μmol/L). SAH was induced by the injection of the autologous blood into cisterna magna on day 0 and day 2. Angiograph was performed on Day 0 and Day 7. Neurobehavioral scores were evaluated daily. Activation of JNK pathway, the infiltration of leukocytes, and the production of cytokines were examined by morphology, Western blot and ELISA.
Results
Severe cerebral vasospasm was observed in the basilar artery accompanied by the activation of JNK pathways in SAH without treatment and DMSO treated dogs. The JNK inhibitor SP600125 reduced angiographic and morphological vasospasm and improved behavior scores with a concomitant reduction of the activation of JNK, the infiltrated leukocytes and the IL-6 production.
Conclusions
These results indicated that the JNK inhibitor attenuated cerebral vasospasm through suppression of inflammatory response, which may provide a novel therapeutic target for cerebral vasospasm.