| Title | A new rat model of thrombotic focal cerebral ischemia. | | Author(s) | Zhang Z, Zhang RL, Jiang Q, Raman SB, Cantwell L, Chopp M | | Institution | Department of Neurology, Henry Ford Health Science Center, Detroit, Michigan, USA. | | Source | J Cereb Blood Flow Metab 1997 Feb; 17(2):123-35. | | MeSH | Animals
Brain Edema
Brain Ischemia
Carotid Artery, Internal
Cerebral Infarction
Disease Models, Animal
Fibrin
Fibrinolytic Agents
Injections, Intra-Arterial
Intracranial Embolism and Thrombosis
Laser-Doppler Flowmetry
Magnetic Resonance Imaging
Male
Microscopy, Confocal
Microscopy, Electron, Scanning
Parietal Lobe
Rats
Rats, Wistar
Recombinant Proteins
Reproducibility of Results
Thrombin
Thrombolytic Therapy
Tissue Plasminogen Activator
| | Abstract | We developed a fibrin-rich thrombotic focal cerebral ischemic model with reproducible and predictable infarct volume in rats. In male Wistar rats (n = 77), a thrombus was induced at the origin of the middle cerebral artery (MCA) by injection of thrombin via an intraluminal catheter placed in the intracranial segment of the internal carotid artery (ICA). Thrombus induction and consequent ischemic cell damage were examined by histopathological analysis and neurological deficit scoring, and by measuring changes in cerebral blood flow (CBF) using laser-Doppler flowmetery (LDF), perfusion-weighted imaging (PWI), and by diffusion weighted imaging (DWI). Histopathology revealed that a fibrin-rich thrombus localized to the origin of the right MCA. Regional cerebral blood flow (rCBF) in the right parietal cortex was reduced by 34-58% of preinjection levels after injection of thrombin in rats administered 30 U of thrombin (n = 10). Magnetic resonance imaging (MRI) showed a reduction in CBF and a hyperintensity DWI encompassing the territory supplied by the right MCA. The infarct volume in rats administered 80 U of thrombin was 31.29 +/- 12.9% of the contralateral hemisphere at 24 h (n = 13), and 34.7 +/- 16.4% of the contralateral hemisphere at 168 h (n = 6). Rats administered 30 U of thrombin exhibited a hemispheric infarct volume of 34.0 +/- 14.5% (n = 9) at 24 h and 29.7 +/- 13.9% (n = 8) at 168 h. In addition, thrombotic rats (n = 3) treated with recombinant tissue plasminogen activator (rt-PA) (10 mg/kg) 2 h after thrombosis showed that CBF rapidly returned towards preischemic values as measured by PWI. This model of thrombotic ischemia is relevant to thromboembolic stroke in humans and may be useful in documenting the safety and efficacy of thrombolytic intervention as well as for investigating therapies complementary to antithrombotic therapy. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, U.S. Gov't, P.H.S.
| | PubMed ID | 9040491 |
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