UBC Theses and Dissertations
Astrocytes in development and in the injured CNS McGraw, John
After a traumatic injury to the brain or spinal cord, the adult mammalian central nervous system (CNS) has a limited ability to repair itself. The reasons why CNS neurons are unable to grow and make functional connections after injury are beginning to be elucidated. There is evidence to suggest that both the intrinsic response of the neuron to injury and the environment the surrounding injured neuron contribute to the absence of anatomical and functional recovery after axotomy. In the developing chick embryo, the onset of myelination by oligodendrocytes is associated with a transition from a growth V permissive to a growth restrictive extraneuronal environment. This thesis examined the development of astrocytes, another glial cell, in chick development. Astrocytes begin to show a differentiated phenotype at embryonic day 12, which is just prior to the onset of myelination. In the adult, reactive astrocytes are a prominent feature of the glial scar that forms after injury. Although it has never been proven, the astroglial scar is less permissive to axonal growth than the surrounding CNS environment. It was the aim of my research to investigate different methods of reducing or removing the astroglial scar after a spinal cord injury in the adult rat. These approaches included 1) targeted antibody and complement-mediated lysis of astrocytes, 2) the reduction of transforming growth factor beta and 3) the ablation of astrocytes using 1-alpha aminoadipate (L-AAA). Of all these treatments, L-AAA was found to be the most successful at removing astrocytes from the site of injury over a one-week period. In the future, L-AAA may be useful in the investigation of the role astrocyte have in CNS development and regeneration after injury.
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