Faculty Collaboration Database

Simvastatin increases endothelial nitric oxide synthase and ameliorates cerebral vasospasm resulting from subarachnoid hemorrhage. Stroke 2002 Dec;33(12):2950-6

Date

12/07/2002

Pubmed ID

12468796

DOI

10.1161/01.str.0000038986.68044.39

Scopus ID

2-s2.0-0036901538 (requires institutional sign-in at Scopus site)   227 Citations

Abstract

BACKGROUND AND PURPOSE: Endothelial nitric oxide synthase (eNOS) activity is decreased after subarachnoid hemorrhage (SAH). Simvastatin increases eNOS activity. We hypothesized that simvastatin would increase eNOS protein and ameliorate SAH-induced cerebral vasospasm.

METHODS: Mice were treated with subcutaneous simvastatin or vehicle for 14 days and then subjected to endovascular perforation of the right anterior cerebral artery or sham surgery. Three days later, neurological deficits were scored (5 to 27; 27=normal), and middle cerebral artery diameter and eNOS protein were measured. The study was repeated, but simvastatin treatment was started after SAH or sham surgery.

RESULTS: In SAH mice, simvastatin pretreatment increased middle cerebral artery diameter (SAH-simvastatin=74+/-22 micro m, SAH-vehicle=52+/-18 micro m, P=0.03; sham-simvastatin=102+/-8 micro m, sham-vehicle=105+/-6 micro m). Pretreatment reduced neurological deficits (SAH-simvastatin=25+/-2, SAH-vehicle=20+/-2, P=0.005; sham-simvastatin and sham-vehicle=27+/-0). Simvastatin pretreatment also increased eNOS protein. Simvastatin posttreatment caused a modest increase in middle cerebral artery diameter in SAH mice (SAH-simvastatin=56+/-12 micro m, SAH-vehicle=45+/-4 micro m, P=0.03; sham-simvastatin=92+/-13 micro m, sham-vehicle=99+/-10 micro m) and reduced neurological deficits (SAH-simvastatin=21+/-1, SAH-vehicle=19+/-2, P=0.009). Simvastatin posttreatment did not significantly increase eNOS protein.

CONCLUSIONS: Simvastatin treatment before or after SAH attenuated cerebral vasospasm and neurological deficits in mice. The mechanism may be attributable in part to eNOS upregulation.

Author List

McGirt MJ, Lynch JR, Parra A, Sheng H, Pearlstein RD, Laskowitz DT, Pelligrino DA, Warner DS

MESH terms used to index this publication - Major topics in bold

Animals
Brain
Disease Models, Animal
Endothelium, Vascular
Enzyme Activation
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Injections, Subcutaneous
Male
Mice
Mice, Inbred C57BL
Middle Cerebral Artery
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Simvastatin
Subarachnoid Hemorrhage
Time Factors
Up-Regulation
Vascular Patency
Vasospasm, Intracranial