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Experimental Brain Research

, Volume 182, Issue 2, pp 261–266 | Cite as

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

  • Shih-Yen Tsai
  • Tiffanie M. Markus
  • Ellen M. Andrews
  • Joseph L. Cheatwood
  • April J. Emerick
  • Anis K. Mir
  • Martin E. Schwab
  • Gwendolyn L. Kartje
Research Note

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.

Keywords

Ischemic Stroke Middle Cerebral Artery Occlusion Perivascular Space Prefer Limb Intrathecal Route 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

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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Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Shih-Yen Tsai
    • 1
  • Tiffanie M. Markus
    • 1
    • 2
    • 7
  • Ellen M. Andrews
    • 1
    • 3
  • Joseph L. Cheatwood
    • 1
    • 2
    • 6
  • April J. Emerick
    • 1
    • 2
  • Anis K. Mir
    • 4
  • Martin E. Schwab
    • 5
  • Gwendolyn L. Kartje
    • 1
    • 2
    • 3
    • 6
  1. 1.Neurology and Research ServiceHines VA HospitalHinesUSA
  2. 2.Neuroscience InstituteLoyola University ChicagoMaywoodUSA
  3. 3.Department of Cell Biology, Neurobiology, and AnatomyLoyola University ChicagoMaywoodUSA
  4. 4.Novartis Pharma AGNervous System Research, Neuroregeneration UnitBaselSwitzerland
  5. 5.Brain Research Institute University of Zurich and Department of BiologySwiss Federal Institute of TechnologyZurichSwitzerland
  6. 6.Department of NeurologyLoyola University Medical CenterMaywoodUSA
  7. 7.Vanderbilt University Institute of Imaging ScienceSouth NashvilleUSA

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