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Intrathecal treatment with anti-Nogo-A antibody improves functional recovery in adult rats after stroke

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Abstract

Stroke often results in devastating neurological disabilities with no specific treatment available to improve functional recovery. Neurite growth inhibitory proteins such as Nogo-A play a critical role in impeding regain of function after stroke. We have reported that treatment with anti-Nogo-A antibody using the intracerebroventricular route resulted in improvement of function and neuroplasticity in adult or aged rats after stroke. This present study tested a more clinically accessible route for applying anti-Nogo-A antibodies, the intrathecal route. Anti-Nogo-A or control antibody was administered intrathecally at lower lumbar levels 1 week after middle cerebral artery occlusion in adult rats. Our results show that anti-Nogo-A antibody delivered by this intrathecal route for 2 weeks penetrated into brain parenchyma and bound to myelin-enriched structures such as the corpus callosum and striatal white matter. Animals receiving anti-Nogo-A antibody treatment significantly improved recovery of function on the skilled forelimb reaching task as compared to stroke only and stroke/control antibody animals. These findings show that anti-Nogo-A antibody delivered through the intrathecal route is as effective in restoring lost functions after stroke as the intracerebroventricular route. This is of great importance for the future application of anti-Nogo-A immunotherapy for ischemic stroke treatment.

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Acknowledgments

Supported by the Department of Veterans Affairs, MREP, NIH (Grant NS40960), Neuroscience Institute and Falk Foundation, Novartis Pharmatheuticals, and the Swiss NSF. We thank Dr. Chung-Sung Sung (VGH Taipei, Taiwan) for assisting in intrathecal catheterization, and Sam and Josh Rosales for their technical assistance.

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Author notes

  1. Tiffanie M. Markus

    Present address: Vanderbilt University Institute of Imaging Science, R-1302 Medical Center North, 1161 21st Ave, South Nashville, TN, 37232, USA

Authors and Affiliations

  1. Neurology and Research Service, Hines VA Hospital, Roosevelt Road and Fifth Avenue, Hines, IL, 60141, USA

    Shih-Yen Tsai, Tiffanie M. Markus, Ellen M. Andrews, Joseph L. Cheatwood, April J. Emerick & Gwendolyn L. Kartje

  2. Neuroscience Institute, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL, 60153, USA

    Tiffanie M. Markus, Joseph L. Cheatwood, April J. Emerick & Gwendolyn L. Kartje

  3. Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Chicago, 2160 S. First Avenue, Maywood, IL, 60153, USA

    Ellen M. Andrews & Gwendolyn L. Kartje

  4. Novartis Pharma AG, Nervous System Research, Neuroregeneration Unit, CH 4002, Basel, Switzerland

    Anis K. Mir

  5. Brain Research Institute University of Zurich and Department of Biology, Swiss Federal Institute of Technology, Winterthurerstrasse 190, 8057, Zurich, Switzerland

    Martin E. Schwab

  6. Department of Neurology, Loyola University Medical Center, 2160 S. First Avenue, Maywood, IL, 60153, USA

    Joseph L. Cheatwood & Gwendolyn L. Kartje

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  1. Shih-Yen Tsai
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  2. Tiffanie M. Markus
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  8. Gwendolyn L. Kartje
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Correspondence to Shih-Yen Tsai.

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Tsai, SY., Markus, T.M., Andrews, E.M. et al. Intrathecal treatment with anti-Nogo-A antibody improves functional recovery in adult rats after stroke. Exp Brain Res 182, 261–266 (2007). https://doi.org/10.1007/s00221-007-1067-0

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  • DOI: https://doi.org/10.1007/s00221-007-1067-0

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