Reduction of brain injury by antithrombotic agent acutobin after middle cerebral artery ischemia/reperfusion in the hyperglycemic rat.
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.
Wei
Jing-na
JN
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Hall MRI Laboratory 1143, Galveston, TX 77555-1143, USA.
Wang
Qing-chuan
QC
Liu
Guang-fen
GF
Ezell
Edward L
EL
Quast
Michael J
MJ
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003435:Crotalid Venoms / Q000627:therapeutic use; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006943:Hyperglycemia / Q000188:drug therapy / Q000503:physiopathology*; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D015424:Reperfusion; D013917:Thrombin / Q000627:therapeutic use; D013997:Time Factors
D003435:Crotalid Venoms; D005343:Fibrinolytic Agents; D013917:Thrombin; C508893:acutobin, Deinagkistrodon acutus