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THE EFFECTS OF AGE AND GEOMETRY ON AXONAL GROWTH AND REGENERATION: A TISSUE SECTION CULTURE APPROACH

Pettigrew, David Brent
http://rave.ohiolink.edu/etdc/view?acc_num=ucin960925569

Abstract Details

2000, PhD, University of Cincinnati, Medicine : Interdisciplinary (Medical Science Scholars, Neuroscience).
Axonal growth is reduced with aging in several models of brain plasticity. These reductions are assumed to contribute to corresponding reductions in behavioral plasticity that occur with aging. Specifically of interest was whether the aged brain is a less permissive substrate for axonal growth in the absence of injury. To assess the baseline substrate properties of the aged brain, explants of sympathetic ganglia were cultured onto cryostat sections of young and aged forebrain and the extent of neurite outgrowth from these explants was measured. The extent of growth varied significantly between brain regions but was not reduced with aging. These data suggest that age-related reductions in axonal growth within the brain are due to age-related changes in the interactions between living cells rather than reduced baseline substrate properties. 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.
Keith Crutcher, Ph.D (Advisor)
194 p.
Biology, Neuroscience
Axonal Regeneration; Aging; White Matter; Glial Scarring; Axon Guidance

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Citations

  • Pettigrew, D. B. (2000). THE EFFECTS OF AGE AND GEOMETRY ON AXONAL GROWTH AND REGENERATION: A TISSUE SECTION CULTURE APPROACH [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin960925569

    APA Style (7th edition)

  • Pettigrew, David. THE EFFECTS OF AGE AND GEOMETRY ON AXONAL GROWTH AND REGENERATION: A TISSUE SECTION CULTURE APPROACH. 2000. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin960925569.

    MLA Style (8th edition)

  • Pettigrew, David. "THE EFFECTS OF AGE AND GEOMETRY ON AXONAL GROWTH AND REGENERATION: A TISSUE SECTION CULTURE APPROACH." Doctoral dissertation, University of Cincinnati, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=ucin960925569

    Chicago Manual of Style (17th edition)

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