Atorvastatin reduction of intravascular thrombosis, increase in cerebral microvascular patency and integrity, and enhancement of spatial learning in rats subjected to traumatic brain injury.
OBJECTIVE
Atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects, such as promoting angiogenesis, increasing fibrinolysis, and reducing inflammatory responses, and has shown promise in enhancing recovery in animals with traumatic brain injury (TBI) and stroke. The authors tested the effect of atorvastatin on vascular changes after TBI.


METHODS
Male Wistar rats subjected to controlled cortical impact injury were perfused at different time points with fluorescein isothiocyanate (FITC)--conjugated dextran 1 minute before being killed. Spatial memory function had been measured using a Morris Water Maze test at various points before and after TBI. The temporal profile of intravascular thrombosis and vascular changes was measured on brain tissue sections by using a microcomputer imaging device and a laser confocal microscopy. The study revealed the following results. 1) Vessels in the lesion boundary zone and hippocampal CA3 region showed a variety of damage, morphological alterations, reduced perfusion, and intraluminal microthrombin formation. 2) Atorvastatin enhanced FITC-dextran perfusion of vessels and reduced intravascular coagulation. 3) Atorvastatin promoted the restoration of spatial memory function.


CONCLUSIONS
These results indicated that atorvastatin warrants investigation as a potential therapeutic drug for TBI.
Lu
Dunyue
D
Department of Neurosurgery, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
Mahmood
Asim
A
Goussev
Anton
A
Schallert
Timothy
T
Qu
Changsheng
C
Zhang
Zheng Gang
ZG
Li
Yi
Y
Lu
Mei
M
Chopp
Michael
M
D000818:Animals; D000069059:Atorvastatin; D001930:Brain Injuries / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008297:Male; D008568:Memory / Q000187:drug effects*; D008833:Microcirculation / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013917:Thrombin / Q000187:drug effects / Q000378:metabolism; D014654:Vascular Patency / Q000187:drug effects
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D013917:Thrombin