Chronic paracetamol treatment induced an increase in pro-inflammatory cytokine expression in the rat brain with cortical spreading depression

Abstract

The present study aims to investigate the effect of chronic paracetamol (APAP) treatment on the expression of pro-inflammatory cytokines (IL-1α and TNF-α) in the cortical spreading depression (CSD) animal model. Rats were divided into a control, CSD only, APAP with and without CSD activation group. A single and daily APAP (200 mg/kg BW, intraperito-neally) treatment for a period of 5, 15, and 30 days was injected into the APAP treated group whereas a vehicle was injected into the control group for comparison. The expression of pro-inflammatory cytokines in the cerebral cortex was studied by immunohistochemistry and western blot analysis. The results showed that short-term APAP treatment (single dose and 5 days) as well as CSD activation alone had no effect on the expression of pro-inflammatory cytokines in the cerebral cortex. However, chronic APAP treatment (15 and 30 days) either with or without CSD activation induced an increase in the number of IL-1α and TNF-α immunoreactive cells as compared with those observed in controls. The results obtained from western blot analysis were correlated with those from immunohistochemical studies. The present study suggests that chronic APAP treatment leads to an increase in the pro-inflammatory cytokine (IL-1α and TNF-α) expression in the brain.