| First Author | Mizushima H | Year | 2002 |
| Journal | J Comp Neurol | Volume | 448 |
| Issue | 2 | Pages | 203-16 |
| PubMed ID | 12012430 | Mgi Jnum | J:77037 |
| Mgi Id | MGI:2180928 | Doi | 10.1002/cne.10262 |
| Citation | Mizushima H, et al. (2002) Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1. J Comp Neurol 448(2):203-16 |
| abstractText | 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. |
