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Extended Middle Cerebral Artery Occlusion (MCAO) Model to Mirror Stroke Patients Undergoing Thrombectomy

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Abstract

Stroke remains a leading global cause of death and disability. In the last decade, the therapeutic window for mechanical thrombectomy has increased from a maximum of 6 to 24 h and beyond. While endovascular advancements have improved rates of recanalization, no post-stroke pharmacotherapeutics have been effective in enhancing neurorepair and recovery. New experimental models are needed to closer mimic the human patient. Our group has developed a model of transient 5-h occlusion in rats to mimic stroke patients undergoing thrombectomy. Our procedure was designed specifically in aged rats and was optimized based on sex in order to keep mortality and extent of injury consistent between aged male and female rats. This model uses a neurological assessment modeled after the NIH Stroke Scale. Finally, the potential for translation between our rat model of stroke and humans was assessed using comparative gene expression for key inflammatory genes. This model will be useful in the evaluation of therapeutic targets to develop adjuvant treatments for large vessel occlusion during the thrombectomy procedure.

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Acknowledgements

Beverly Meacham (Senior Radiology Technologist) and David Powell (Assistant Professor) with The Magnetic Resonance Imaging and Spectroscopy Center. NIH Shared Instrumentation Program Grant for the 7T ClinScan. S10 (1S10RR029541-01).

Funding

National Institute of Neurological Disorders and Stroke (5R01NS091146-04).

Author information

Author notes

  1. Sarah J. Messmer and Kathleen E. Salmeron contributed equally to this body of work

Authors and Affiliations

  1. Center for Advanced Translational Stroke Science, University of Kentucky, Lexington, KY, USA

    Sarah J. Messmer, Jacqueline A. Frank, Justin F. Fraser & Keith R. Pennypacker

  2. Department of Behavioral Science, University of Kentucky, Lexington, KY, USA

    Christopher J. McLouth

  3. Department of Neurology, University of Kentucky, Lexington, KY, USA

    Sarah J. Messmer, Jacqueline A. Frank, Justin F. Fraser & Keith R. Pennypacker

  4. Department of Neuroscience, University of Kentucky, Lexington, KY, USA

    Kathleen E. Salmeron, Tyler C. Hammond, Ai-Ling Lin, Justin F. Fraser & Keith R. Pennypacker

  5. Department of Neurological Surgery, University of Kentucky, Lexington, KY, USA

    Justin F. Fraser

  6. Department of Radiology, University of Kentucky, Lexington, KY, USA

    Douglas E. Lukins & Justin F. Fraser

  7. Sanders-Brown Center On Aging, University of Kentucky, Lexington, KY, USA

    Tyler C. Hammond & Ai-Ling Lin

  8. Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY, USA

    Ai-Ling Lin

  9. F. JosephHalcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY, USA

    Ai-Ling Lin

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  1. Sarah J. Messmer
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Contributions

SM performed surgeries, and SM and JF analyzed the data. KS wrote the manuscript with exception of methods (SM and JF). CM analyzed behavioral data. DL analyzed infarct and edema data. TH and AL analyzed the cerebral perfusion data. KRP, SM, and JF planned experiments and edited the manuscript. JFF performed human thrombectomy surgeries and JFF and KRP oversaw the formulation of the project and edited the manuscript.

Corresponding author

Correspondence to Keith R. Pennypacker.

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KRP and JFF co-founders of Cerelux, LLC.

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Messmer, S.J., Salmeron, K.E., Frank, J.A. et al. Extended Middle Cerebral Artery Occlusion (MCAO) Model to Mirror Stroke Patients Undergoing Thrombectomy. Transl. Stroke Res. 13, 604–615 (2022). https://doi.org/10.1007/s12975-021-00936-y

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  • DOI: https://doi.org/10.1007/s12975-021-00936-y

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