HMG-CoA reductase inhibitor, atorvastatin, promotes sensorimotor recovery, suppressing acute inflammatory reaction after experimental intracerebral hemorrhage.
OBJECTIVE
Statins have neuroprotective effects on ischemic stroke. They modify the endothelial function, increase blood flow, and inhibit thrombus formation, which are independent of lipid-lowering effects. However, whether statins have a protective effect toward hemorrhagic stroke is yet unknown. To test this possibility, we attempted to determine the effect of atorvastatin on experimental intracerebral hemorrhage (ICH).


METHODS
ICH was induced using stereotaxic infusion of collagenase into the left basal ganglia in adult rats. Atorvastatin (1 mg/kg or 10 mg/kg) or phosphate-buffered saline was administered for 2 weeks. To monitor the sensorimotor deficits, limb placing and Rotorod tests were performed. Hematoma volume, brain water content, and hemispheric atrophy were analyzed. Immunohistochemical staining for myeloperoxidase (MPO), microglia (OX42), inducible nitric oxide synthase (iNOS), or endothelial nitric oxide synthase (eNOS) was performed. Perihematomal cell death was determined by TUNEL staining.


RESULTS
The atorvastatin-treated ICH group showed better performance on Rotorod and limb placing tests when compared with the vehicle-treated group (P<0.01). The hematoma volumes between groups were not different, but the brain water content and hemispheric atrophy were reduced in the atorvastatin-treated ICH group. Atorvastatin reduced TUNEL-positive cells, iNOS expression, and MPO-positive or OX42-positive cells in the perihematomal regions in a dose-dependent manner, whereas it increased eNOS expression.


CONCLUSIONS
The present study shows that atorvastatin reduces the perihematomal cell death via antiinflammation, which is associated with sensorimotor recovery after experimental ICH.
Jung
Keun-Hwa
KH
Stroke and Neural Stem Cell Laboratory in Clinical Research Institute, Department of Neurology, Seoul National University Hospital, Seoul National University, Seoul, South Korea.
Chu
Kon
K
Jeong
Sang-Wuk
SW
Han
So-Young
SY
Lee
Soon-Tae
ST
Kim
Jin-Young
JY
Kim
Manho
M
Roh
Jae-Kyu
JK
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D001284:Atrophy; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006406:Hematoma / Q000473:pathology; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011597:Psychomotor Performance; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018696:Neuroprotective Agents; D011758:Pyrroles; D000069059:Atorvastatin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat