Recombinant osteopontin attenuates experimental cerebral vasospasm following subarachnoid hemorrhage in rats through an anti-apoptotic mechanism.
Brain Res
; 1611: 74-83, 2015 Jun 22.
Article
in En
| MEDLINE
| ID: mdl-25779039
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Subarachnoid Hemorrhage
/
Apoptosis
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Vasospasm, Intracranial
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Osteopontin
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Brain Res
Year:
2015
Document type:
Article
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS