| First Author | Hara H | Year | 1997 |
| Journal | J Cereb Blood Flow Metab | Volume | 17 |
| Issue | 4 | Pages | 370-5 |
| PubMed ID | 9143219 | Mgi Jnum | J:42304 |
| Mgi Id | MGI:1095526 | Doi | 10.1097/00004647-199704000-00002 |
| Citation | Hara H, et al. (1997) Attenuation of transient focal cerebral ischemic injury in transgenic mice expressing a mutant ICE inhibitory protein. J Cereb Blood Flow Metab 17(4):370-5 |
| abstractText | We used transgenic mice expressing a dominant negative mutation of interleukin-1 beta converting enzyme (ICE) (C285G) in a model of transient focal ischemia in order to investigate the role of ICE in ischemic brain damage. Transgenic mutant ICE mice (n = 11) and wild-type littermates (n = 9) were subjected to 3 h of middle cerebral artery occlusion followed by 24 h of reperfusion. Cerebral infarcts and brain swelling were reduced by 44% and 46%, respectively. Neurological deficits were also significantly reduced. Regional CBF, blood pressure, core temperature, and heart rate did not differ between groups when measured for up to 1 h after reperfusion. Increases in immunoreactive IL-1 beta levels, observed in ischemic wild-type brain at 30 min after reperfusion, were 77% lower in the mutant strain, indicating that proIL-1 beta cleavage is inhibited in the mutants. DNA fragmentation was reduced in the mutants 6 and 24 h after reperfusion. Hence, endogenous expression of an ICE inhibitor confers resistance to cerebral ischemia and brain swelling. Our results indicate that downregulation of ICE expression might provide a useful therapeutic target in cerebral ischemia. |
