scholarly journals Exacerbation of Ischemic Brain Damage by Localized Striatal Injection of Interleukin-1β in the Rat

1998 ◽  
Vol 18 (8) ◽  
pp. 833-839 ◽  
Author(s):  
R. Paul Stroemer ◽  
Nancy J. Rothwell

Interleukin-1β (IL-1β) has been implicated in ischemic brain damage. The site of action of IL-1β in such damage is not known, but we have demonstrated previously that injection of the interleukin-1 receptor antagonist (IL-1ra) in the striatum but not the cortex of rats inhibits damage caused by permanent middle cerebral artery occlusion. The present study investigated the site of action of IL-1β on ischemic damage by examining the effects of intracerebroventricular, striatal, or cortical injection of recombinant IL-1β at the onset of permanent middle cerebral artery occlusion in the rat. Intracerebroventricular injection of IL-1β (2.5 ng) significantly increased infarct volume in the striatum (35%, P < 0.0001) and in the cortex (44%, P < 0.0001) compared with vehicle treatment. Direct injection of IL-1β into the striatum also increased infarct volume in both the striatum (36%, P < 0.0001) and the cortex (38%, P < 0.0001), whereas injection of IL-1β into the cortex failed to affect infarct volume in either the striatum or the cortex. Cortical injection of a higher dose of IL-1β (20 ng) also failed to affect ischemic damage in either the striatum or the cortex. Injection of IL-1β into the striatum contralateral to the infarction had no effect on striatal damage in the ischemic hemisphere, but did increase cortical damage by 18% ( P < 0.0001). In separate groups of animals, IL-1β (2.5 ng) was injected into either the striatum or the cortex, and body temperature was recorded continuously in conscious free-moving animals by remote telemetry. Injection of IL-1β at either site failed to influence body temperature, suggesting that exacerbation of brain damage by striatal injection of IL-1β is not caused by effects on body temperature. These results imply that IL-1β exacerbates ischemic damage by specific actions in the striatum where it can influence damage at distant sites in the cortex.

2003 ◽  
Vol 23 (5) ◽  
pp. 531-535 ◽  
Author(s):  
Rachel D. Wheeler ◽  
Herve Boutin ◽  
Omar Touzani ◽  
Giamal N. Luheshi ◽  
Kiyoshi Takeda ◽  
...  

There is now extensive evidence to show that the cytokine interleukin-1 (IL-1) contributes directly to reversible and permanent ischemic brain damage in rodents. Because interleukin-18 (IL-18) shares many structural and functional similarities with IL-1, the authors tested the hypothesis that IL-18 contributes directly to ischemic brain damage in mice exposed to focal, reversible (15-minute or 30-minute) middle cerebral artery occlusion. IL-18 expression was not induced acutely by middle cerebral artery occlusion, and deletion of the IL-18 gene (IL-18 knockout mice) did not affect infarct volume. The present results suggest that IL-18 does not contribute to acute ischemic brain damage.


2002 ◽  
Vol 22 (11) ◽  
pp. 1297-1302 ◽  
Author(s):  
Antonio Cárdenas ◽  
María A. Moro ◽  
Juan C. Leza ◽  
Esther O'Shea ◽  
Antoni Dávalos ◽  
...  

A short ischemic event (ischemic preconditioning [IPC]) can result in a subsequent resistance to severe ischemic injury (ischemic tolerance [IT]). Although tumor necrosis factor-α (TNF-α) contributes to the brain damage, its expression and neuroprotective role in models of IPC have also been described. However, the role of TNF-α convertase (TACE) in IPC and IT is not known. Using in vitro models, the authors previously demonstrated that TACE is upregulated after ischemic brain damage. In the present study, the authors used a rat model of transient middle cerebral artery occlusion as IPC to investigate TACE expression, its involvement in TNF-α release, and its role in IT. Western blot analysis showed that TACE expression is increased after IPC. Ischemic preconditioning caused TNF-α release, an effect that was blocked by the selective TACE inhibitor BB-1101 (10 mg · kg−1 · day−1; SHAM, 1,050 ± 180; IPC, 1,870 ± 290; IPC + BB, 1,320 ± 260 ng/mg; n = 4, P < 0.05). Finally, IPC produced a reduction in infarct volume, which was inhibited by treatment with BB-1101 and with anti–TNF-α (10 μg/5 doses; SHAM + permanent middle cerebral artery occlusion [pMCAO], 335 ± 20; IPC + pMCAO, 244 ± 14; IPC + BB + pMCAO, 300 ± 6; IPC + anti-TNF + pMCAO, 348 ± 22 mm3; n = 6–10, P < 0.05). Taken together, these data demonstrate that TACE is upregulated after IPC, plays a major role in TNF-α shedding in IPC, and has a neuroprotective role in IT.


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