An Examination of The Mechanisms by Which Neural Precursors Augment Recovery Following Spinal Cord Injury: A Key Role for Remyelination
Authors: Gregory W. Hawryluk, Stefania Spano, Derek Chew, Shelly Wang, Mark Erwin, Mahmood Chamankhah, Nicole Forgione, Michael G. Fehlings
Source: Cell Transplantation
Publisher: Cognizant Communication Corporation
Abstract:Background: The mechanism(s) by which neural precursor cells (NPCs) enhance functional recovery from spinal cord injury (SCI) remain unclear.Methods: Spinal cord injured rats were transplanted with wild type mouse NPCs, shiverer NPCs unable to produce myelin, dead NPCs or media. Most animals also received minocycline, cyclosporin and peri-lesional infusion of trophins. Motor function was graded according to the BBB scale. H&E/LFB staining was used to assess grey and white matter, cyst and lesional tissue. Mature oligodendrocytes and ED1+ inflammatory cells were quantitated. Confocal and electron microscopy assessed the relationship between transplanted cells and axons.Results: Pharmacotherapy and trophin infusion preserved grey matter, white matter and oligodendrocytes. Trophin infusion also significantly increased cyst, lesional tissue volume as well as inflammatory infiltrate and it reduced functional recovery. Animals transplanted with wild-type NPCs showed greatest functional recovery; animals transplanted with shiverer NPCs performed worst. Wild-type NPCs remyelinated host axons. Shiverer NPCs ensheath axons but did not produce MBP.Conclusions: These results suggest that remyelination by NPCs is an important contribution to functional recovery following SCI. Shiverer NPCs may prevent remyelination by endogenous cells capable of myelin formation. These findings suggest that remyelination is an important therapeutic target following SCI.
Appeared or available online: January 28, 2013