Activation of JAK2/STAT pathway in cerebral cortex after experimental traumatic brain injury of rats

Abstract

The janus kinase/signal transducer and activator of transcription (JAK/STAT) is one of the main pathways downstream of cytokine receptors and growth factor receptors by transducing signals from cell surface to the nucleus. In this study, we aimed to survey the role of JAK2/STAT pathway in the progress of TBI. Right parietal cortical contusion in rats was induced by the Feeney free falling model. The activation of JAK2, STAT1 and STAT3 in pericontusional cortex was determined by Western blotting, electrophoretic mobility shift assay (EMSA), immunohistochemistry and immunofluorescence. Moreover, we assessed the neurological recovery (using Neurological Severity Scores (NSS)) of rats under the pretreatment of a JAK2 inhibitor, AG490. Western blotting revealed that expression of p-JAK2, p-STAT1 and p-STAT3 increased immediately, peaked at 3h after TBI and decreased thereafter, and the activation could be inhibited by AG490. Immunohistochemical study showed that JAK2/STAT pathway was activated in both neurons and astrocytes at 3h after TBI. STAT3-specific binding activity was obviously enhanced after TBI and down-regulated after AG490 administration. The higher NSS of TBI+AG490 group revealed a worse behavior recovery when compared with TBI+DMSO group. Our results suggest that the JAK2/STAT pathway is activated in pericontusional cortex of rats, and may be involved in the neurological function recovery after TBI.