Conclusions
Minocycline plays a neuroprotective role by attenuating early brain injury after experimental SAH. The therapeutic mechanism of minocycline may be mediated by the inhibition of P2X4R on microglia.
Methods
SAH was induced in male Sprague-Dawley rats by endovascular perforation. The rats were treated with minocycline (25 mg/kg or 50 mg/kg) or saline at 2 hand 12 h post SAH. Neurological function, cerebral hemorrhage, and edema were scored at 48 h post SAH. Cell death and P2X4 receptor (P2X4R) expression were observed in the prefrontal cortex (PFC).
Results
Treatment with a highdose of minocycline significantly improved the neurological function score, and attenuated cerebral hemorrhage and edema. Low-dose minocycline could reduce hemorrhage, but the effect on neurological deficits and brain edema was not obvious. Minocycline treatment could alleviate neuronal apoptosis in the PFC, which was related to reduced expression of inflammatory cytokines. Immunofluorescence showed that P2X4R on microglia was activated after SAH. Minocycline treatment inhibited P2X4R activation and further suppressed the phosphorylation of downstream p38 MAPK. Conclusions: Minocycline plays a neuroprotective role by attenuating early brain injury after experimental SAH. The therapeutic mechanism of minocycline may be mediated by the inhibition of P2X4R on microglia.