Tuesday December 12 - Special Neuroscience Seminar - 12:00 noon Rm 928 McDonnell Science. Dr. David Pettigrew, Dept. of Neurosurgery, Univ. of Cincinnati, "The Effects of Myelin Geometry on Axonal Growth and Regeneration: A Tissue Section Culture Approach"

Axonal regeneration is limited in the CNS following injury. Previous investigations have identified axon-growth inhibitors associated with myelin, inspiring the hypothesis that myelinated fiber tracts cannot support axonal growth. Other studies, however, have shown that white matter can support axonal growth in vivo. We sought to reconcile these contrasting lines of evidence by reassessing the capacity of white matter in cryostat sections of brain and spinal cord to support neurite growth from cultured sympathetic neurons. White matter was found to support long neurite growth oriented in parallel with the fiber tract and inhibit non-parallel growth. This geometric growth constraint is likely due to myelin-associated inhibitors since neurites extending on myelin-deficient tracts or on myelinated tracts in the presence of factors known to deactivate these inhibitors were significantly less parallel.

To assess the effects of injury-induced tissue disruption on axonal growth in the absence of glial scarring, spinal cord or sciatic nerve was crushed and immediately frozen to prevent glial scarring. When longitudinal cryostat sections were used as substrata for sympathetic neurons, neurites extended on uncrushed tissue, crossed crushed gray matter but did not cross crushed white matter or crushed sciatic nerve. These data suggest that injuries to fiber tracts are barriers to axonal regeneration in the absence of glial scarring and that restoration of tissue organization is key in permitting axonal regeneration.