title: Delayed thrombosis after traumatic brain injury in rats.
abstract: Secondary thrombosis may contribute to cerebral ischemia caused by traumatic brain injury (TBI). In this study, we sought to investigate the temporal and spatial profiles of intravascular thrombosis and to evaluate the effect of atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor, on thrombosis after TBI. Young male Wistar rats weighing 350-400 g were subjected to controlled cortical impact injury, and were sacrificed at 1 and 4 h, and 1, 3, 8, and 15 days after TBI (5 rats/time point), respectively. For the evaluation of the effects of atorvastatin on intravascular thrombosis, rats were subjected to TBI, and subsequently atorvastatin (1 mg/kg) was orally administered starting 1 day after TBI and then daily until sacrifice at 3, 8, and 15 days after TBI (5 rats/time point). Before sacrifice of animals, blood was withdrawn and employed for the measurement of von Willibrand factor and platelet activity using enzyme-linked immunoabsorbant assay (ELISA). Brain tissues were prepared for histological analysis. The data show that (1) delayed thrombosis is present in the lesion boundary zone and in the hippocampal CA3 region, starting at 1-4 h, peaking at 1-3 days, and then declining at 8 and 15 days after TBI; (2) intravascular thrombosis also occurs in the other areas of cortex, striatum, and corpus callosum, but with a scattered distribution; (3) delayed thrombi are composed of platelets, fibrin, and vWF; and (4) reduction of the plasma vWF level and platelet activity by atorvastatin decreases delayed thrombosis after TBI. These data suggest that atorvastatin reduces intravascular thrombosis attributed to hemostatic disturbances caused by TBI.
authors.affiliation: Department of Neurosurgery, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.
authors.forename: Dunyue
authors.initials: D
authors.lastname: Lu
authors.forename: Asim
authors.initials: A
authors.lastname: Mahmood
authors.forename: Anton
authors.initials: A
authors.lastname: Goussev
authors.forename: Changsheng
authors.initials: C
authors.lastname: Qu
authors.forename: Zheng Gang
authors.initials: ZG
authors.lastname: Zhang
authors.forename: Michael
authors.initials: M
authors.lastname: Chopp
mesh_terms: D000818:Animals; D000069059:Atorvastatin; D001779:Blood Coagulation Factors / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D005337:Fibrin / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D020767:Intracranial Thrombosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D001779:Blood Coagulation Factors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D005337:Fibrin; D000069059:Atorvastatin