In vivo indomethacin treatment causes microglial activation in adult mice

The current study was undertaken to study the role of prostaglandins in reg ulating microglial activation. Mice were treated with indomethacin (2 mu g/ ml) in their drinking water to selectively inhibit cyclooxygenase activity. After 4-8 days, the effect of inhibiting prostaglandin synthesis on microg lial activity was evaluated. This was accomplished by analyzing microglial expression of Mac-1 (C3 complement receptor) as an indicator of activation. Mac-1 expression was assessed by immunohistochemistry of fixed brain cryos ections, and by flow cytometric analysis of immunostained single cell suspe nsions. Both methods demonstrated that compared to age-matched, untreated c ontrols, brains of indomethacin-treated mice had increased levels of Mac-1 expression, suggesting an increase in the state of microglial activation. T hese results demonstrate the importance of prostaglandins in down regulatin g microglial activity, and that inhibition of prostaglandin synthesis with indomethacin may act to increase the reactivity of the brain's immune syste m.