Background: Post-ischemic mild hypothermia is a robust neuroprotective agent for stroke therapy, but the complete mechanism of action is not yet fully understood. Therefore, as inflammation plays an important role in the ischemic cascade, the effect of hypothermia on pro-inflammatory cytokines, more specifically interleukin-1 beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha), was investigated. Methods: Endothelin-1 (Et-1), a potent vasoconstrictor, is infused adjacent to the middle cerebral artery in order to elicit a focal cerebral ischemic insult in male Wistar rats. In this model, the core and the penumbra are represented respectively by the striatum and the cortex. Two hours of mild hypothermia (33°C), starting 20 minutes after the onset of the insult, is compared to normothermic (37°C) conditions. The levels of IL-1beta and TNF-alpha are determined, via ELISA, in the ipsi- and contralateral striatum and cortex at 8 and 24 hours after administration of Et-1. Infarct size at these time points is assessed by cresylviolet staining. Results: Twenty-four hours after the insult, mild hypothermia reduced the infarct size by half. In both hypothermic and normothermic animals, the levels of IL-1beta and TNF-alpha were increased on the contra- as well as the ipsilateral striatum and cortex, compared to control animals. In the penumbra, hypothermia significantly enhanced the level of IL-1beta and significantly reduced those of TNF-alpha, compared to normothermia. No significant changes were seen in the striatum. Conclusion: Hypothermia has a significant effect on the pro-inflammatory cytokines in the penumbra, but is without effect in the core of the insult.
|Number of pages||1|
|Journal||International Journal of Stroke|
|Issue number||supplement 1|
|Publication status||Published - Sep 2008|
|Event||Finds and Results from the Swedish Cyprus Expedition: A Gender Perspective at the Medelhavsmuseet - Stockholm, Sweden|
Duration: 21 Sep 2009 → 25 Sep 2009