Recombinant tissue plasminogen activator promotes, and progesterone attenuates, microglia/macrophage M1 polarization and recruitment of microglia after MCAO stroke in rats.

BACKGROUND

Tissue plasminogen activator (tPA) is one of the few approved treatments for stroke, but its effects on the phenotype of microglia/macrophages are poorly understood. One of its side effects is an increase in the inflammatory response leading to neuronal cell damage and death in the ischemic cascade after stroke. Injury-induced activated microglia/macrophages can have dual functions as pro-inflammatory (M1) and anti-inflammatory (M2) factors in brain injury and repair. Recent studies show that progesterone (PROG) is a potent anti-inflammatory agent which affects microglia/macrophage expression after brain injury.

OBJECTIVE

We examined the interaction of tPA-induced expression of microglia/macrophage phenotypes and PROG's anti-inflammatory effects.

RESULTS

tPA treatment increased the recruitment of microglia/macrophages, the polarity of M1 reactions, the expression of MIP-1α in neurons and capillaries, and the expression of MMP-3 compared to vehicle, and PROG modulated these effects.

CONCLUSIONS

PROG treatment attenuates tPA-induced inflammatory alterations in brain capillaries and microglia/macrophages both in vivo and in vitro and thus may be a useful adjunct therapy when tPA is given for stroke.