Abstract
Recombinant human interleukin-1 receptor antagonist (rhIL-1ra) markedly protects against focal cerebral ischaemia in the rat, implicating endogenous IL-1 in the events leading to cerebral infarction. The present experiments investigated the effect of intracerebroventricular (i.c.v.) administration of IL-1β or rhIL-1ra on ischaemia damage and physiological parameters after permanent middle cerebral artery occlusion in the rat. IL-1β (5 ng, i.c.v.) markedly (92%) enhanced infarct volume and caused a significant rise in body temperature, but rhIL-1ra (10 μg, i.c.v.) significantly reduced infarct volume and did not significantly affect heart rate, blood pressure, or body temperature. rhIL-1ra administered 30 min before, or at the time of ischaemia significantly reduced infarct volume in cortex (55 and 60%, respectively) and striatum (52 and 41%, respectively). rhIL-1ra administered 30 min after ischaemia significantly reduced total and cortical infarct volume (26 and 29%, respectively), but did not significantly protect striatal tissue. The effects of rhIL-1ra were still evident in both cortex and striatum 7 days after ischaemia. These results support the role of IL-1 in ischaemic brain damage, revealing potent, sustained, neuroprotective effects of rhIL-1ra in the cortex and striatum, which cannot be attributed directly to changes in physiological parameters.
| Original language | English |
|---|---|
| Pages (from-to) | 932-940 |
| Number of pages | 8 |
| Journal | Journal of Cerebral Blood Flow and Metabolism |
| Volume | 16 |
| Issue number | 5 |
| Publication status | Published - 1996 |
Keywords
- Cerebral ischaemia
- Interleukin-1 receptor antagonist
- Rat