Recently, a number of non-beneficial effects of chronic treatment with
paracetamol (
APAP) have been reported in several systems, including circulatory system. In this study, the effects of acute (1 hour) and chronic (30 days)
APAP treatments 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 (200 mg/kg
body weight) or once-daily
APAP treatment over 30 days was intraperitoneally injected into the acute and chronic
APAP treated groups, respectively. CSD was induced by topical application of
potassium chloride on the parietal cortex. Ultrastructural alterations and the expressions of
cell adhesion molecules (ICAM-1 and VCAM-1) of the cerebral microvessels were monitored in all experimental groups. The results demonstrated that the induction of CSD caused ultrastructural alterations of the cerebral endothelial cells, as indicated by increases in microvillous and pinocytic formations and swelling of the astrocytic foot plates. The expression of
ICAM-1 was significantly elevated in the CSD groups as compared with the control groups. Pretreatment with
APAP 1 hour prior to CSD activation attenuated the alterations induced by CSD. However, chronic
APAP treatment resulted in an enhancement of the ultrastructural alterations and the expressions of
cell adhesion molecules in the cerebral microvessels that were induced by CSD. Interestingly, the rats that received chronic
APAP treatment alone exhibited higher degrees of ultrastructural alterations and
ICAM-1 expression than those in the control group. Based on these results, we suggest that short-term treatment with
APAP has no effect on cerebral microvessels and that chronic
APAP treatment can alter cerebral microvasculature, especially when combined with CSD activation.