Abstract
Adverse effect of paracetamol (APAP) treatment has been recently reported in several systems.In this study, effectsofAPAP treatments at 3 different time points (0, 15, and 30 days) on cerebral microvessels in a cortical spreading depression (CSD) migraine animal model were investigated. Rats were divided into control, CSD only, and APAP treatment with or without CSD groups. A single dose of APAP (200 mg/kg body weight, i.p.) was injected into the 0 day APAP-treated group while once-daily APAP treatment over 15 and 30 days was given to the 15 and 30 day APAP-treated groups, respectively. CSD was induced by topical application of KCl on parietal cortex. Ultrastructural alterations and expressions of cell adhesion molecules (ICAM-1 and VCAM-1) of cerebral microvessels were investigated in all animal groups. The results demonstrated that induction of CSD increased ultrastructural alterationsofcerebral endothelial cells and expressionsof ICAM-1 and VCAM-1. A single APAP pretreatment could decrease those alterations induced by CSD. In contrast, ultrastructural alterations and expressions of cell adhesion molecules were enhanced in rats that received chronic APAP treatment (15 and 30 days) in combination with CSD. Additionally, chronic APAP treatment alone could also increase those alterations as compared with control groups.
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