title: Rosiglitazone attenuates early brain injury after experimental subarachnoid hemorrhage in rats.
abstract: Early brain injury (EBI) plays a crucial role in the pathological progress of subarachnoid hemorrhage (SAH). This study was designed to determine whether rosiglitazone protects the brain against EBI in rats, and discuss the role of the anti-apoptotic mechanism mediated by Bcl-2 family proteins in this neuroprotection. 86 male Sprague-Dawley rats were divided into the sham group, the SAH+ vehicle group and the SAH+ rosiglitazone group. SAH was induced via an endovascular perforation technique and rosiglitazone (3mg/kg) or vehicle was administered. Mortality, neurological scores, brain water content, Evans blue dye assay, TUNEL stain assay, Gelatin zymography, and western blot analysis were performed. Rosiglitazone significantly improved mortality, neurological scores, brain water content, blood brain barrier (BBB) and apoptosis compared with the vehicle group within 24h after SAH. The TUNEL staining assay demonstrated that apoptosis was ameliorated. Cleaved Caspase-3 and MMP-9 expression was reduced, whereas Bcl-2 and p-Bad was markedly preserved by rosiglitazone. A significant elevation of p-Akt was detected after rosiglitazone treatment. Our study demonstrated that rosiglitazone plays a neuroprotective role in EBI after SAH via attenuation of BBB disruption, brain edema and apoptosis.
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Jianru
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Jingyin
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, China. Electronic address: d-chengao@zju.edu.cn.
authors.forename: Gao
authors.initials: G
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001929:Brain Edema / Q000209:etiology / Q000517:prevention & control; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology*; D053148:Caspase 3 / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000401:mortality / Q000473:pathology; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019938:Cyclin D1; D053148:Caspase 3; D020780:Matrix Metalloproteinase 9
keywords: Akt pathway; Apoptosis; Bcl-2; Early brain injury; PPARγ; Subarachnoid hemorrhage