Improvement in neurological outcome after administration of atorvastatin following experimental intracerebral hemorrhage in rats.
OBJECTIVE
Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor, improves neurological functional outcome, reduces cerebral cell loss, and promotes regional cellular plasticity when administered after intracerebral hemorrhage (ICH) in rats.


METHODS
Autologous blood was stereotactically injected into the right striatum in rats, and atorvastatin was administered orally beginning 24 hours after ICH and continued daily for 1 week. At a dose of 2 mg/kg, atorvastatin significantly reduced the severity of neurological deficit from 2 to 4 weeks after ICH. The area of cell loss in the ipsilateral striatum was also significantly reduced in these animals. Consistent with previous study data, higher doses of atorvastatin (8 mg/kg) did not improve functional outcome or reduce the extent of injury. Histochemical stains for markers of synaptogenesis, immature neurons, and neuronal migration revealed increased labeling in the region of hemorrhage in the atorvastatin-treated rats.


CONCLUSIONS
Analysis of the data in this study indicates that atorvastatin improves neurological recovery after experimental ICH and may do so in part by increasing neuronal plasticity.
Seyfried
Donald
D
Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan 48202, USA. nsdos@neuro.hfh.edu
Han
Yuxia
Y
Lu
Dunyue
D
Chen
Jieli
J
Bydon
Ali
A
Chopp
Michael
M
D000818:Animals; D000069059:Atorvastatin; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D009420:Nervous System / Q000503:physiopathology*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects; D012720:Severity of Illness Index; D016896:Treatment Outcome
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin