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