Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1
Mizushima, H; Zhou, CJ; Dohi, K; Horai, R; Asano, M; Iwakura, Y; Hirabayashi, T; Arata, S; Nakajo, S; Takaki, A; Ohtaki, H; Shioda, S
| HERO ID | 1656047 |
|---|---|
| In Press | No |
| Year | 2002 |
| Title | Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin-1 |
| Authors | Mizushima, H; Zhou, CJ; Dohi, K; Horai, R; Asano, M; Iwakura, Y; Hirabayashi, T; Arata, S; Nakajo, S; Takaki, A; Ohtaki, H; Shioda, S |
| Journal | Journal of Comparative Neurology |
| Volume | 448 |
| Issue | 2 |
| Page Numbers | 203-216 |
| 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. |
| Doi | 10.1002/cne.10262 |
| Pmid | 12012430 |
| Wosid | WOS:000175862800007 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000175862800007 |
| Is Public | Yes |
| Language Text | English |
| Keyword | global ischemia; knockout mice; neurodegeneration; mitogen-activated protein kinase; nitric oxide |