Atorvastatin reduces neurological deficit and increases synaptogenesis, angiogenesis, and neuronal survival in rats subjected to traumatic brain injury.
Statins administered postischemia promote functional improvement in rats, independent of their capability to lower cholesterol. We therefore tested the effect of statin treatment on traumatic brain injury (TBI) in rats. Atorvastatin was orally administered (1 mg/kg/day) to Wistar rats starting 1 day after TBI for 7 consecutive days. Control animals received saline. Modified Neurological Severity Scores and Corner tests were utilized to evaluate functional response to treatment. Bromodeoxyuridine (BrdU, 100 mg/kg) was also intraperitoneally injected daily for 14 consecutive days to label the newly generated endothelial cells. Rats were sacrificed at day 14 after TBI, and the brain samples were processed for immunohistochemical staining. Atorvastatin administration after brain injury significantly reduced the neurological functional deficits, increased neuronal survival and synaptogenesis in the boundary zone of the lesion and in the CA3 regions of the hippocampus, and induced angiogenesis in these regions. The results suggest that atorvastatin may provide beneficial effects in experimental TBI.
Department of Neurosurgery, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Dunyue
D
Lu
Anton
A
Goussev
Jieli
J
Chen
Paul
P
Pannu
Yi
Y
Li
Asim
A
Mahmood
Michael
M
Chopp
D000284:Administration, Oral; D000818:Animals; D000069059:Atorvastatin; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D006538:Heptanoic Acids / Q000008:administration & dosage*; D007150:Immunohistochemistry; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism
D006538:Heptanoic Acids; D018696:Neuroprotective Agents; D011758:Pyrroles; D016708:Synaptophysin; D000069059:Atorvastatin