Reduction of brain injury by antithrombotic agent acutobin after middle cerebral artery ischemia/reperfusion in the hyperglycemic rat

Brain Res. 2004 Oct 1;1022(1-2):234-43. doi: 10.1016/j.brainres.2004.07.019.

Abstract

In vivo magnetic resonance imaging (MRI) was used to observe the effect of acutobin, a purified thrombin-like enzyme (TLE), isolated from the snake venom of Deinagkistrodon acutus, on MRI-detected brain lesion volume and tissue perfusion deficit in a hyperglycemic rat right middle cerebral artery occlusion/reperfusion (MCAO/R) model. Acutobin (0.75 U/ml) was intravenously injected with a dosage of 2.5 U/kg body weight 30 min after MCAO (MCAO duration=60 min) and again 24 h after reperfusion. Multislice diffusion weighted imaging (DWI) and single-slice dynamic bolus tracking gradient echo (GE) imaging were sequentially acquired before and after MCAO/R. DWI-detected lesion volume was significantly (p<0.05) reduced by 24-31% from 350+/-45, 369+/-45 and 374+/-36 mm(3) in the saline-treated group to 239+/-17, 282+/-26 and 259+/-32 mm(3) at 3, 4 and 24 h after reperfusion in the acutobin-treated group, respectively. Residual cerebral blood flow (CBF) in the right hemisphere recovered and remained at approximately 80% of normal perfusion over the measurement period in the acutobin-treated group, compared to approximately 40% in the saline-treated group. Mortality at 1 week after MCAO/R in the acutobin-treated group was significantly lower (25% mortality) than the saline control group (85% mortality). Our results indicate that acutobin improves brain tissue perfusion and reduces infarct volume and mortality in the hyperglycemic rat MCAO/R model.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Injuries / drug therapy*
  • Brain Injuries / etiology
  • Brain Injuries / pathology
  • Brain Mapping
  • Cerebrovascular Circulation / drug effects
  • Crotalid Venoms / therapeutic use
  • Disease Models, Animal
  • Fibrinolytic Agents / therapeutic use*
  • Hyperglycemia / drug therapy
  • Hyperglycemia / physiopathology*
  • Infarction, Middle Cerebral Artery / physiopathology*
  • Magnetic Resonance Imaging / methods
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology
  • Reperfusion*
  • Thrombin / therapeutic use
  • Time Factors

Substances

  • Crotalid Venoms
  • Fibrinolytic Agents
  • Thrombin
  • acutobin, Deinagkistrodon acutus