Abstract
The cytokine interleukin-1 (IL-1) has been implicated in ischemic brain damage, because the IL-1 receptor antagonist markedly inhibits experimentally induced neuronal loss. However, to date, no studies have demonstrated the involvement of endogenous IL-1alpha and IL- 1beta in neurodegeneration. We report here, for the first time, that mice lacking IL-1alpha/beta (double knockout) exhibit markedly reduced neuronal loss and apoptotic cell death when exposed to transient cardiac arrest. Furthermore, we show that, despite the reduced neuronal loss, phosphorylation of JNK/SAPK (c-Jun NH2- terminal protein kinase/stress activated protein kinase) and p38 enzymes remain elevated in IL-1 knockout mice. In contrast, the inducible nitric oxide (iNOS) immunoreactivity after global ischemia was reduced in IL-1 knockout mice as compared with wild-type mice. The levels of nitrite (NO(2) (-)) and nitrate (NO(3) (-)) in the hippocampus of wild-type mice were increased with time after ischemia-reperfusion, whereas the increase was significantly inhibited in IL-1 knockout mice. These observations strongly suggest that endogenous IL-1 contributes to ischemic brain damage, and this influence may act through the release of nitric oxide by iNOS.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.