title: Rosiglitazone ameliorates astrocyte over-activation and inflammatory cytokine release induced by global cerebral ischemia/reperfusion.
abstract: Global cerebral ischemia (GCI) is a leading cause of mortality worldwide and remains the primary cause of long-term neurological disability. Astrocyte over-activation and extensive neuron loss in the ischemic brain are the characteristic pathological features of cerebral ischemia. Rosiglitazone (RSG) is a peroxisome-proliferating activating receptor-γ agonist known for its anti-inflammatory activity. Previous studies have suggested that RSG is able to exert neuroprotection in numerous acute and chronic brain injury models. However, whether RSG treatment is involved in astrocyte over-activation and inflammatory reaction in the cortex remains unclear. The aim of the present study was to investigate whether RSG treatment improved functional impairment induced following GCI and protected against cortex neuron loss, and to elucidate the potential mechanisms underlying these functions. Rats were randomly divided into three groups: Sham-operated, GCI and RSG treatment groups. The RSG treatment group was treated with 2 mg/kg RSG immediately following GCI. The results demonstrated that RSG treatment significantly reduced infarct volume and neuron survival rates in addition to increasing function recovery. Furthermore, these results correlate with a reduction in astrocyte over-activation and inflammatory cytokines in the rat cortex. However, no significant changes in glutamate transporter-1 expression levels were observed following RSG treatment compared with the GCI rats. The results of this investigation providein vivoevidence that RSG significantly protected rats against ischemia-reperfusion-induced brain injury. In addition, RSG may exert neuroprotective effects by inhibiting astrocyte over-activation, and thereby reducing the levels of inflammatory cytokines in the GCI-injured brain. All data revealed that RSG may be a potential neuroprotective agent for cerebral ischemia.
authors.affiliation: Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Shanling
authors.initials: S
authors.lastname: Ren
authors.affiliation: Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Lv
authors.affiliation: Department of Neurology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
keywords: astrocyte over-activation; global cerebral ischemia; glutamate transporter-1; inflammatory; rats; rosiglitazone