Abstract
Minocycline has been demonstrated to be neuroprotective after spinal cord injury (SCI). However, the cellular consequences of minocycline treatment on the secondary injury response are poorly understood. We examined the ability of minocycline to reduce oligodendrocyte apoptosis, microglial/macrophage activation, corticospinal tract (CST) dieback, and lesion size and to improve functional outcome after SCI. Adult rats were subjected to a C7-C8 dorsal column transection, and the presence of apoptotic oligodendrocytes was assessed within the ascending sensory tract (AST) and descending CST in segments (3-7 mm) both proximal and distal to the injury site. Surprisingly, the numbers of dying oligodendrocytes in the proximal and distal segments were comparable, suggesting more than the lack of axon-cell body contiguity played a role in their demise. Minocycline or vehicle control was injected into the intraperitoneal cavity 30 min and 8 hr after SCI and thereafter twice daily for 2 d. We report a reduction of apoptotic oligodendrocytes and microglia within both proximal and distal segments of the AST after minocycline treatment, using immunostaining for active caspase-3 and Hoechst 33258 staining in combination with cell-specific markers. Activated microglial/macrophage density was reduced remote to the lesion as well as at the lesion site. Both CST dieback and lesion size were diminished after minocycline treatment. Footprint analysis revealed improved functional outcome after minocycline treatment. Thus, minocycline ameliorates multiple secondary events after SCI, rendering this clinically used drug an attractive candidate for SCI treatment trials.
Bibliography
Stirling, D. P., Khodarahmi, K., Liu, J., McPhail, L. T., McBride, C. B., Steeves, J. D., Ramer, M. S., & Tetzlaff, W. (2004). Minocycline Treatment Reduces Delayed Oligodendrocyte Death, Attenuates Axonal Dieback, and Improves Functional Outcome after Spinal Cord Injury. The Journal of Neuroscience, 24(9), 2182â2190.
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Dates
Type | When |
---|---|
Created | 21 years, 6 months ago (March 3, 2004, 1:02 p.m.) |
Deposited | 2 years, 4 months ago (April 13, 2023, 11:57 a.m.) |
Indexed | 2 days, 17 hours ago (Sept. 3, 2025, 6:58 a.m.) |
Issued | 21 years, 6 months ago (March 3, 2004) |
Published | 21 years, 6 months ago (March 3, 2004) |
Published Online | 21 years, 6 months ago (March 3, 2004) |
Published Print | 21 years, 6 months ago (March 3, 2004) |
@article{Stirling_2004, title={Minocycline Treatment Reduces Delayed Oligodendrocyte Death, Attenuates Axonal Dieback, and Improves Functional Outcome after Spinal Cord Injury}, volume={24}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.5275-03.2004}, DOI={10.1523/jneurosci.5275-03.2004}, number={9}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Stirling, David P. and Khodarahmi, Kourosh and Liu, Jie and McPhail, Lowell T. and McBride, Christopher B. and Steeves, John D. and Ramer, Matt S. and Tetzlaff, Wolfram}, year={2004}, month=mar, pages={2182–2190} }