title: Recombinant osteopontin attenuates experimental cerebral vasospasm following subarachnoid hemorrhage in rats through an anti-apoptotic mechanism.
abstract: Cerebral vasospasm (CVS) is an important pathological process following subarachnoid hemorrhage (SAH). Osteopontin (OPN), a pleiotropic extracellular glycoprotein, has been reported to be able to induce MKP-1 in the spastic cerebral arteries and prevent vasospasm after SAH. The purpose of this study was to investigate the protective effects of recombinant OPN (r-OPN) on CVS following SAH and the underlying mechanisms associated with its anti-apoptotic effect. Eighty male Sprague Dawley rats (weighing 300-375g) were randomly assigned to four groups: (1) sham+vehicle (n=20), (2) SAH+vehicle (n=20), (3) SAH+OPN0.03 (0.03μg) (n=20), (4) SAH+OPN0.1 (0.1μg) (n=20). The double injection model of cisterna magna was performed on day 0 and 48h after the first induction. r-OPN was administered intraventricularly nearly 30min after the first SAH. After neurological score assessment, rats were sacrificed 72h after the first SAH. The cross-sectional area and thickness of basilar arteries (BA) were measured under Hematoxylin-eosin (H&E) staining. Endothelial cell apoptosis was identified by terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. Immunohistochemistry was used to assess the expression of p-Akt and cleaved caspase-3 in BA. Western blot analysis was applied to evaluate the expression of p-Akt, cleaved caspase-3, Bax and Bcl-2 in BA. r-OPN improved neurological scores and attenuated vasospasm. r-OPN significantly reduced expression of cleaved caspase-3 and Bax in BA following SAH, and increased the level of p-Akt and Bcl-2, coupled with reduced apoptosis of endothelial cell in BA. These results demonstrate that r-OPN can attenuate vasospasm after SAH through a suppressed apoptotic response, which may provide a novel therapeutic target for cerebral vasospasm.
authors.affiliation: Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. Electronic address: iverjun@hotmail.com.
authors.forename: Junchi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Mindi
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China. Electronic address: lsluo@sohu.com.
authors.forename: Liangsheng
authors.initials: L
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D001488:Basilar Artery / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D008297:Male; D053495:Osteopontin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000378:metabolism; D020301:Vasospasm, Intracranial / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D011994:Recombinant Proteins; C506897:Spp1 protein, rat; D053495:Osteopontin
keywords: Apoptosis; Cerebral vasospasm; Osteopontin; Subarachnoid hemorrhage