Spinal Cord Cells Proliferate After Injury

Occasionally we set out looking for one thing and, much to our delight, find another. This happened to Dr. Mark Tuszynski and his collaborators at the University of California in San Diego while doing research on spinal cord injury. Human recovery from spinal cord injury is modest at best. Dr, Tuszynski’s hypothesis was “cell division after primate Spinal Cord Injury is primarily limited to inflammatory cell lineages”. Yet, their experiments yielded an unexpected and exciting finding: while macrophages and microglia increased initially following injury, after seven weeks the number of these cells decreases, while the number of oligodendrocytes, astrocytes, and infiltrating Schwann actually cells increase. For the layperson, Dr. Tuszynski was expecting to find cells involved in repairing injury being born, but unexpectedly found cells that support neurons being born. This finding provides hope that this “natural compensatory response” can be targeted for possible therapies. In particular, the encouraging possibility of “increasing the number and modifying the fate of endogenous stem cells”.

Stereology played an important part in these experiments. Dr. Tuszynski and his group used double and triple confocal immunolabeling; BRDU-immunostaining was combined with various markers including those for inflammatory cells and glial cells. They used Stereo Investigator’s Optical Fractionator probe. The sampling parameters were determined so that at least 200 cells were counted for a given newly-born cell type per spinal cord. Systematic random sampling was performed and guard zones were set at a little less than 20% of the section thickness.

See: Yang, H., et.al., 2006 Endogenous Neurogenesis Replaces Oligodendrocytes and Astrocytes after Primate Spinal Cord Injury. Journal of Neuroscience 26(8):2157-2166

Images and and cell numbers determined using stereology
Figure 1. Lesion and BrdU labeling. A, Nissl-stained section of C6 lesion site in subject 4, 7 months after injury. Peri-les, Perilesion tissue; IW, intact white matter; IG, intact gray matter. B, Abundant BrdU labeling in perilesioned region of subject 4, 7 months after injury. C, In contrast, intact subject exhibits only sparse BrdU labeling at C6 level. D, Mean density of BrdU-labeled cells in four monkeys with C6 –C7 spinal cord lesions. Extensive cell division occurs in perilesion region, and newly dividing cells are also evident on the contralateral, intact side of spinal cord and on lesioned side caudal to injury. Significantly more cells are present in perilesioned region than in other spinal cord areas ( p_0.001). E, Total numbers of BrdU-labeled cells determined stereologically in each of four lesioned subjects at various time points after injury and in one intact monkey. Subj., Subject; Les. Vol., lesion volume. Scale bars: A, 720 µm; (in B) B, C, 20 µm. Error bars represent SEM.