Concomitant cortical expression of TNF-α and IL-1β mRNAs follows early response gene expression in transient focal ischemia

The expression of tumor necrosis factor alpha and interleukin 1 beta mRNAs was significantly increased in the rat ischemic cortex following temporary occlusion of the middle cerebral artery with reperfusion, suggesting that these cytokines play an important role in the inflammatory response associated with focal ischemia.

Abstract

The expression of tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) mRNAs was significantly increased in the rat ischemic cortex following temporary occlusion of the middle cerebral artery (TMCAO) with reperfusion. Northern blot analysis demonstrated that the induction of TNF-alpha and IL-1 beta mRNAs occurred as early as 1 h after reperfusion, exhibiting a 4.6-fold increase (p < 0.05, n = 4) and 6.8-fold increase (p < 0.05, n = 4) in the ischemic cortex over control, respectively. TNF-alpha mRNA reached its peak at 3 h (8.0-fold, p < 0.05), whereas IL-1 beta mRNA reached its peak at 6 h (29.5-fold, p < 0.05). Both cytokine mRNA levels remained elevated for up to 2 d after reperfusion. In contrast to the time course of these cytokine mRNAs, c-fos and zif268 mRNAs, two early response genes, displayed a greater and earlier time-response profile. The early induction of c-fos and zif268 mRNAs in temporary brain ischemia with reperfusion suggests their roles in transcriptional regulation. The later concomitant expression of TNF-alpha and IL-1 beta suggests that these cytokines play an important role in the inflammatory response associated with focal ischemia.