A rat model of studying tissue-type plasminogen activator thrombolysis in ischemic stroke with diabetes

Stroke. 2012 Feb;43(2):567-70. doi: 10.1161/STROKEAHA.111.635250. Epub 2011 Nov 3.

Abstract

Background and purpose: Poststroke hyperglycemia and diabetes mellitus are associated with lower thrombolytic efficacy and an increased risk of postischemic cerebral hemorrhage. We aimed to develop a rodent model of thrombolysis in diabetic stroke that mimics the clinical situation. Method- Male 6-week Type I diabetic rats (14 weeks old) were subjected to embolic focal stroke and treated with tissue-type plasminogen activator at 1.5 hours. Reperfusion and 24-hour neurological outcomes were measured and compared with nondiabetic control rats.

Results: Diabetic rats exhibited resistance to thrombolytic reperfusion, larger infarction volumes, and increased intracerebral hemorrhage.

Conclusions: This animal model would be relevant to future studies investigating pathophysiological mechanisms and in developing new therapeutic approaches to enhance the efficacy of tissue-type plasminogen activator thrombolysis in stroke patients with diabetes or poststroke hyperglycemia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain Edema / drug therapy
  • Brain Edema / pathology
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Cerebral Hemorrhage / drug therapy
  • Cerebral Hemorrhage / pathology
  • Cerebral Infarction / drug therapy
  • Cerebral Infarction / pathology
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / complications
  • Diabetic Angiopathies / drug therapy*
  • Fibrinolytic Agents / therapeutic use*
  • Immunohistochemistry
  • Intracranial Embolism / drug therapy
  • Intracranial Embolism / pathology
  • Laser-Doppler Flowmetry
  • Male
  • Microcirculation / physiology
  • Nervous System Diseases / etiology
  • Rats
  • Rats, Wistar
  • Stroke / drug therapy*
  • Stroke / etiology
  • Tissue Plasminogen Activator / therapeutic use*

Substances

  • Fibrinolytic Agents
  • Tissue Plasminogen Activator