Jingbo Li1, Shuda Chen1, Jing Fan1, Gao Zhang1, Reng Ren1. 1. Neurocritical Care Unit, the Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, P.R. China.
Abstract
BACKGROUD: The aim of this study was to evaluate the therapeutic effect of minocycline on treating experimental subarachnoid hemorrhage (SAH) in rats and to explore its possible molecular mechanism. 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.
BACKGROUD: The aim of this study was to evaluate the therapeutic effect of minocycline on treating experimental subarachnoid hemorrhage (SAH) in rats and to explore its possible molecular mechanism. 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.
Authors: Thomas Möller; Frédérique Bard; Anindya Bhattacharya; Knut Biber; Brian Campbell; Elena Dale; Claudia Eder; Li Gan; Gwenn A Garden; Zoë A Hughes; Damien D Pearse; Roland G W Staal; Faten A Sayed; Paul D Wes; Hendrikus W G M Boddeke Journal: Glia Date: 2016-06-01 Impact factor: 7.452