title: Thrombin inhibition by argatroban ameliorates early brain injury and improves neurological outcomes after experimental subarachnoid hemorrhage in rats.
abstract: OBJECTIVE
  We investigated the role of thrombin in early brain injury after subarachnoid hemorrhage (SAH).
  
  
  METHODS
  The standard intravascular perforation model was used to produce experimental SAH in Sprague Dawley rats. Low-dose (0.3 mg/h) and high-dose (0.9 mg/h) argatroban, a direct thrombin inhibitor, were evaluated for effects on brain edema, blood-brain barrier (BBB) disruption, apoptotic cell death, inflammatory marker, and neurological outcomes after SAH.
  
  
  RESULTS
  Both doses of argatroban attenuated BBB disruption; however, only high-dose was effective in lowering edema in all brain regions, reducing cell death, and inflammatory marker expression, and improving neurological outcomes.
  
  
  CONCLUSIONS
  Thrombin inhibition by argatroban improves neurological outcomes and provides neuroprotection against acute events after SAH such as BBB disruption, brain edema, and cell death.
authors.affiliation: Department of Physiology, Loma Linda University, Loma Linda, Calif 92354, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugawara
authors.forename: Vikram
authors.initials: V
authors.lastname: Jadhav
authors.forename: Robert
authors.initials: R
authors.lastname: Ayer
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Chen
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; C031942:argatroban