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Focal embolic cerebral ischemia in the rat

Nature Protocols volume 10, pages 539–547 (2015)Cite this article

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Abstract

Animal models of focal cerebral ischemia are well accepted for investigating the pathogenesis and potential treatment strategies for human stroke. Occlusion of the middle cerebral artery (MCA) with an endovascular filament is a widely used model to induce focal cerebral ischemia. However, this model is not amenable to thrombolytic therapies. As thrombolysis with recombinant tissue plasminogen activator (rtPA) is a standard of care within 4.5 h of human stroke onset, suitable animal models that mimic cellular and molecular mechanisms of thrombosis and thrombolysis of stroke are required. By occluding the MCA with a fibrin-rich allogeneic clot, we previously developed an embolic model of MCA occlusion in the rat, which recapitulates the key components of thrombotic development and of thrombolytic therapy of rtPA observed from human ischemic stroke. Here we describe in detail the surgical procedures of our model, including preparing emboli from rat donors. These procedures can be typically completed within ∼30 min, and they are highly adaptable to other strains of rats, as well as mice, in both sexes. Thus, this model provides a powerful tool for translational stroke research.

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Figure 1: Preparation of clot and measurement of catheter.
Figure 2: MCAO and ischemic lesion.
Figure 3: Angiogram, CBF and thrombosis.
Figure 4: Neurological outcome.

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Acknowledgements

This work is supported by US National Institutes of Health grants R01NS079612 (Z.G.Z.) and R01AG037506 (M.C.).

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Authors and Affiliations

  1. Department of Neurology, Henry Ford Hospital, Detroit, Michigan, USA

    Li Zhang, Rui Lan Zhang, Quan Jiang, Guangliang Ding, Michael Chopp & Zheng Gang Zhang

  2. Department of Physics, Oakland University, Rochester, Michigan, USA

    Michael Chopp

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Contributions

R.L.Z., Z.G.Z. and M.C. conceptualized experiments. R.L.Z., L.Z. and Z.G.Z. performed the surgeries and histological analysis. Q.J. and G.D. performed MRI experiments and analyzed MRI data. L.Z., Z.G.Z. and M.C. wrote the manuscripts.

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Correspondence to Zheng Gang Zhang.

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Zhang, L., Zhang, R., Jiang, Q. et al. Focal embolic cerebral ischemia in the rat. Nat Protoc 10, 539–547 (2015). https://doi.org/10.1038/nprot.2015.036

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