Purpose
Proteinase-activated receptor 2 (PAR-2) is involved in many cellular functions, but its roles in the cerebral ischemia were unclear yet. We investigated the effect of PAR-2 in cerebral ischemia by using PAR-2 knockout mice. Furthermore, we studied how PAR-2 affects the intracellular signaling and astrocytes function.
Method
One hour of tMCAO was induced in male PAR-2 knockout and wild type mice, and the brains were removed at 5 min, 8, and 24 hr after reperfusion. The infarction was evaluated by cresyl violet staining at 24 hr after reperfusion. PAR-2 and p-ERK expression were detected by immunostaining and western blotting. The activation of astroglia was evaluated by GFAP staining; TUNEL staining was used as markers of apoptosis.
Results
PAR-2 was normally distributed mainly in neurons, and strongly up-regulated at 8 to 24 hours after tMCAO. Deficiency of PAR-2 gene significantly increased the infarct volume and the number of TUNEL positive cells at 24 h of reperfusion. The strong neuronal expression of p-ERK was induced with a peak at 5 min, which was significantly reduced in PAR-2 KO mice. Astroglial activation was also greatly inhibited at 24 hours after tMCAO in PAR-2 KO mice.
Conclusion
These results demonstrate that the deficiency of PAR-2 gene increases the acute ischemic cerebral injury, associating with suppression of neuronal ERK activation and reactive astroglial activation. (See Figure 1).
