OBJECTIVE: In the present study, MRI has been used to investigate therapeutic intervention with statins in a model of permanent focal cerebral ischemia in rat. METHODS AND RESULTS: Brain ischemia was induced in rats by the permanent occlusion of middle cerebral artery (MCAO) and the brain infarct size followed up in alive animals 2, 24, and 48 hours after MCAO, using the trace of apparent diffusion coefficient [Tr(D)] maps and T2-weighted images. In vehicle-treated rats, the infarct volumes increased by 38.5% and 89% after 24 and 48 hours, respectively, compared with the damage detected at 2 hours after MCAO. Treatment with simvastatin (20 mg/kg) after MCAO prevented the increase in brain infarct volume occurring at 24 hours and induced a 46.6% reduction after 48 hours. This effect was similar to that observed when simvastatin was administered before the induction of focal ischemia. T2W-MRI images confirmed these findings. The neuroprotective effects of simvastatin were paralleled by an increase in endothelial NO synthase immunoreactivity, detectable in the brain of simvastatin-treated rats. CONCLUSIONS: Statins, in addition to their preventive effect on cerebral ischemia, exert a neuroprotective role in the attenuation of brain damage after acute stroke.

Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage / L. Sironi, M. Cimino, U. Guerrini, A. M. Calvio, B. Lodetti, M. Asdente, W. Balduini, R. Paoletti, E. Tremoli. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 23:2(2003 Feb 01), pp. 322-327. [10.1161/01.ATV.0000044458.23905.3B]

Treatment with statins after induction of focal ischemia in rats reduces the extent of brain damage

L. Sironi;U. Guerrini;M. Asdente;R. Paoletti;E. Tremoli
2003-02-01

Abstract

OBJECTIVE: In the present study, MRI has been used to investigate therapeutic intervention with statins in a model of permanent focal cerebral ischemia in rat. METHODS AND RESULTS: Brain ischemia was induced in rats by the permanent occlusion of middle cerebral artery (MCAO) and the brain infarct size followed up in alive animals 2, 24, and 48 hours after MCAO, using the trace of apparent diffusion coefficient [Tr(D)] maps and T2-weighted images. In vehicle-treated rats, the infarct volumes increased by 38.5% and 89% after 24 and 48 hours, respectively, compared with the damage detected at 2 hours after MCAO. Treatment with simvastatin (20 mg/kg) after MCAO prevented the increase in brain infarct volume occurring at 24 hours and induced a 46.6% reduction after 48 hours. This effect was similar to that observed when simvastatin was administered before the induction of focal ischemia. T2W-MRI images confirmed these findings. The neuroprotective effects of simvastatin were paralleled by an increase in endothelial NO synthase immunoreactivity, detectable in the brain of simvastatin-treated rats. CONCLUSIONS: Statins, in addition to their preventive effect on cerebral ischemia, exert a neuroprotective role in the attenuation of brain damage after acute stroke.
Magnetic Resonance Imaging; Animals; Cerebral Infarction; Simvastatin; Brain Chemistry; Brain Damage, Chronic; Disease Models, Animal; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Neuroprotective Agents; Endothelium, Vascular; Rats; Cerebral Cortex; Rats, Sprague-Dawley; Brain Mapping; Nitric Oxide Synthase Type III; Nitric Oxide Synthase; Brain Ischemia; Up-Regulation; Brain Injuries; Immunohistochemistry; Male; Cerebral Arteries
Settore BIO/14 - Farmacologia
ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY
Article (author)
File in questo prodotto:
File Dimensione Formato  
322.full.pdf

non disponibili

597.54 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/185849
Citazioni
  • ???jsp.display-item.citation.pmc??? 45
  • Scopus 174
  • ???jsp.display-item.citation.isi??? 159
social impact