TY - JOUR
T1 - HMG-CoA reductase inhibitor, atorwastatin, promotes sensorimotor recovery, suppressing acute inflammatory after experimental intracerebral hemorrhage
AU - Jung, Keun Hwa
AU - Chu, Kon
AU - Jeong, Sang Wuk
AU - Han, So Young
AU - Lee, Soon Tae
AU - Kim, Jin Young
AU - Kim, Manho
AU - Roh, Jae Kyu
PY - 2004/7
Y1 - 2004/7
N2 - Background and Purpose-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. Conclusion-The present study shows that atorvastatin reduces the perihematomal cell death via antiinflammation, which is associated with sensorimotor recovery after experimental ICH.
AB - Background and Purpose-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. Conclusion-The present study shows that atorvastatin reduces the perihematomal cell death via antiinflammation, which is associated with sensorimotor recovery after experimental ICH.
KW - Apoptosis
KW - Brain edema
KW - HMG-CoA reductase inhibitors
KW - Inflammation
KW - Intracerebral hemorrhage
UR - http://www.scopus.com/inward/record.url?scp=3042688440&partnerID=8YFLogxK
U2 - 10.1161/01.STR.0000131270.45822.85
DO - 10.1161/01.STR.0000131270.45822.85
M3 - Article
C2 - 15166393
AN - SCOPUS:3042688440
SN - 0039-2499
VL - 35
SP - 1744
EP - 1749
JO - Stroke
JF - Stroke
IS - 7
ER -