Long-term protective effect of atorvastatin in permanent focal cerebral ischemia.
Statins exert beneficial effects in brain diseases including stroke. Here, we investigated whether oral prophylactic atorvastatin provides long-term neuroprotection and functional recovery in permanent middle cerebral artery occlusion (pMCAO), and whether cerebral hemodynamics are affected. Male Long-Evans rats were treated with 10 mg/kg oral atorvastatin for 14 days and subjected to pMCAO. Cerebral hemodynamics were measured by bolus tracking MRI and laser Doppler flowmetry (LDF). Infarct volume was quantified at 1 week by T2-MRI and at 3 weeks by histology. Rats were also subjected to neuroscoring and cylinder test. The number of animals per group was 10. The infarct volumes were 100.8 +/- 8.2 and 47.3 +/- 5.5 mm(3) in vehicle, and 68.7 +/- 11.0 and 28.6 +/- 3.82 mm(3) in atorvastatin group at 7 and 21 days post-ischemia, respectively (mean +/- SEM). Atorvastatin significantly reduced infarct volume both at 7 and 21 days (P = 0.04 and 0.03, respectively, 1-way ANOVA). Interestingly, no improvement in cerebral hemodynamic parameters was observed in atorvastatin treated animals. The vehicle group recovered normal neuroscore at day 13, whereas atorvastatin group recovered already at day 10 after pMCAO. All treatment groups preferred to use the unaffected forelimb for rearing in Cylinder test, whereas the defected forelimb use was minimal in all groups. These results suggest that oral atorvastatin protects cerebral tissue against the subsequent pMCAO without influencing cerebral hemodynamic parameters, and it may well be that persons with ongoing atorvastatin treatment benefit in the incidence of stroke.
Yrjänheikki
Juha
J
Cerebricon Ltd, Microkatu 1, Kuopio, Finland. juha.yrjanheikki@cerebricon.com
Koistinaho
Jari
J
Kettunen
Mikko
M
Kauppinen
Risto A
RA
Appel
Kurt
K
Hüll
Michael
M
Fiebich
Bernd L
BL
D000818:Animals; D000069059:Atorvastatin; D001522:Behavior, Animal; D001775:Blood Circulation / Q000187:drug effects / Q000502:physiology; D020520:Brain Infarction / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D016291:Dizocilpine Maleate / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D020318:Rats, Long-Evans; D020127:Recovery of Function / Q000187:drug effects*; D013194:Staining and Labeling / Q000379:methods; D013995:Time; D013997:Time Factors
D006538:Heptanoic Acids; D018696:Neuroprotective Agents; D011758:Pyrroles; D016291:Dizocilpine Maleate; D000069059:Atorvastatin