title: Brain injury and cerebrovascular fibrin deposition correlate with reduced antithrombotic brain capillary functions in a hypertensive stroke model.
abstract: Hemostasis factors may influence the pathophysiology of stroke. The role of brain hemostasis in ischemic hypertensive brain injury is not known. We studied ischemic injury in spontaneously hypertensive rats in relation to cerebrovascular fibrin deposition and activity of different hemostasis factors in brain microcirculation. In spontaneously hypertensive rats subjected to transient middle cerebral artery occlusion versus normotensive Wistar-Kyoto (W-K) rats, infarct and edema volumes were increased by 6.1-fold (P < 0.001) and 5.8-fold (P < 0.001), respectively, the cerebral blood flow (CBF) reduced during middle cerebral artery occlusion (MCAO) by 55% (P < 0.01), motor neurologic score increased by 6.9-fold (P < 0.01), and cerebrovascular fibrin deposition increased by 6.8-fold (P < 0.01). Under basal conditions, brain capillary protein C activation and tissue plasminogen activator activity were reduced in spontaneously hypertensive rats compared with Wistar-Kyoto rats by 11.8-fold (P < 0.001) and 5.1-fold (P < 0.001), respectively, and the plasminogen activator inhibitor-1 antigen and tissue factor activity were increased by 154-fold (P < 0.00001) and 74% (P < 0.01), respectively. We suggest that hypertension reduces antithrombotic mechanisms in brain microcirculation, which may enhance cerebrovascular fibrin deposition and microvascular obstructions during transient focal cerebral ischemia, which results in greater neuronal injury.
authors.affiliation: Department of Neurological Surgery, Children's Hospital Los Angeles, USC School of Medicine, California, USA.
authors.forename: T
authors.initials: T
authors.lastname: Ninomia
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: S R
authors.initials: SR
authors.lastname: Kumar
authors.forename: A
authors.initials: A
authors.lastname: Kim
authors.forename: B V
authors.initials: BV
authors.lastname: Zlokovic
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002196:Capillaries / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D005337:Fibrin / Q000032:analysis / Q000378:metabolism*; D005342:Fibrinolysis / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006487:Hemostasis / Q000502:physiology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D020767:Intracranial Thrombosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008854:Microscopy, Electron; D009460:Neurologic Examination; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011486:Protein C / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020521:Stroke / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013925:Thromboplastin / Q000235:genetics
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D012333:RNA, Messenger; D005337:Fibrin; D013925:Thromboplastin