Simvastatin protects against long-lasting behavioral and morphological consequences of neonatal hypoxic/ischemic brain injury

Citation
W. Balduini et al., Simvastatin protects against long-lasting behavioral and morphological consequences of neonatal hypoxic/ischemic brain injury, STROKE, 32(9), 2001, pp. 2185-2191
Citations number
27
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurology,"Cardiovascular & Hematology Research
Journal title
STROKE
ISSN journal
0039-2499 → ACNP
Volume
32
Issue
9
Year of publication
2001
Pages
2185 - 2191
Database
ISI
SICI code
0039-2499(200109)32:9<2185:SPALBA>2.0.ZU;2-N
Abstract
Background and Purpose-Recent studies suggest that statins (3-hydroxy-3-met hylglutaryl coenzyme A reductase inhibitors) not only reduce the incidence of stroke by lowering cholesterol levels but may also exert neuroprotective effects via a mechanism not related to their lipid-lowering effect. Despit e the growing body of evidence, however, the neuroprotective effect of stat ins in stroke is still controversial. Herein, we studied whether a prophyla ctic administration of simvastatin (Sim) provides significant protection ag ainst brain damage, and we sought to determine its long-lasting behavioral consequences in a neonatal model of hypoxia/ischemia. Methods-Newborn male rats were injected daily from postnatal days 1 to 7 wi th activated Sim (20 mg/kg) or an equivalent volume of vehicle. On postnata l day 7, the rats were subjected to ligation of the right common carotid ar tery, followed by 3 hours of hypoxia or by sham operation. The neuroprotect ive effect of Sim was evaluated after the rats had achieved adulthood by us ing a battery of behavioral tests and histological analysis. Results-Sim-treated ischemic rats performed the circular water maze, the ra dial arm maze, and the multiple-choice water maze significantly better than did vehicle-treated ischemic rats. Furthermore, in contrast to the ischemi c rats, hypoxia/ischemia-injured rats pretreated with Sim were not hyperact ive at weaning and showed less behavioral asymmetry. Consistently, it was f ound that brain damage was significantly attenuated. Conclusions-These findings indicate that prophylactic administration of sta tins may provide a potential neuroprotective strategy leading to an improve ment in functional outcome in ischemic stroke. However, toxicity concern mu st be addressed before these agents can be directed to the asphyxiated fetu s or newborn.