Abstract W P209: Development of a Useful Brain Ischemic Stroke Model via a Transient Occlusion of Middle Cerebral Artery in the Nonhuman Primate
Objectives: Most experimental stroke research is carried out in rodents, but given differences between rodents and human, the nonhuman primate (NHP) models may provide a valuable tool to study the clinical therapy. We developed a surgical method for transient occlusion of the middle cerebral artery (MCA-M1) in the Cynomolgus monkeys to evaluate the MCA territory blood flow, the model stability, animal clinical neurological behavior, morphology changes under magnetic resonance imaging (MRI) and histopathology.
Methods: The left brain sylvian fissure was exposed by a small fronto-temporal craniotomy. The MCA-M1 was exposed by microsurgical dissection and clipped for 4 hours. The brain blood flow was measured in the MCA territory during the ischemia period and early phase of reperfusion period. The clinical neurological examinations and MRI were carried out at regular post-operative course till 4 weeks of stroke.
Results: During MCA occlusion, the MCA territory blood flow was decreased significantly in 80%. This territory was reflowed right after reperfusion and showed an overload in about 20% over pre ischemia flow within 1hr after reperfusion and gradually returned to previous flow (Fig 1). Animal neurological behavior changed significantly within 1 week and became a steady status of neurological impairment. MRI demonstrated extensive MCA territory infarction. Histologically, at the end of 4 week stroke the brain showed a clear board of glia proliferation between infarct and normal brain tissue.
Conclusion: These results indicate a stable ischemic stroke model in cynomolgus monkeys after complete MCA-M1 occlusion, which will be a useful NHP stroke model for stroke research and the clinical therapeutic studies.
Fig 1 Changes in MCA territory blood flow during ischemia-reperfusion period
Author Disclosures: E. Sho: None. Z. Zhu: None. Y. Zhao: None. J. Chen: None. D. He: None. W. Wang: None. X. Tu: None. J. Ma: None. W. Zheng: None.
- © 2014 by American Heart Association, Inc.