The experiments proposed in this study will test the ability of specific brain-derived neurotrophic substances to produce a behavioral improvement when delivered to damaged brain areas. Our laboratory has developed a procedure for deriving specific neurotrophic agents from explant co- cultures of embryonic central nervous system (CNS) structures. These agents are then able to rescue specific CNS neurons damaged in vivo. the experiments proposed here will test whether delivery of these neurotrophic agents to damaged brain areas will also contribute to recovery of a behavioral function impaired by the damage. We will first test whether a macromolecular fraction of conditioned medium (CM) from co-cultures of embryonic rat cortex and diencephalon is able to ameliorate a learning impairment in visual pattern discrimination that results when newborn rats sustain a unilateral posterior cortex removal. We will also determine the relationship between the behavioral effects of this CM fraction delivered to the lesion site and neuron survival in visual system structures with norm direct connections to the lesion site. the specificity of the behavioral effects will be tested by comparing the results with animals receiving similarly prepared CM fractions from co- culture of embryonic structures that normally have no direct connections, or other visual system areas with direct connections. These same experiments will also be conducted in animals receiving unilateral or bilateral visual cortex lesion of the CM fraction from an implanted osmotic pump. The direct contribution to the behavioral improvement of structures showing increased neuroviability in response to the neurotrophic agent, will then be tested by making lesions of those structures following delivery of the CM fraction. The results of these experiments will indicate whether CNS cell products with specific neuron survival-promoting properties may also improve behavioral functions impaired by damage to those neurons.
| Haun, F; Cunningham, T J (1993) Recovery of frontal cortex-mediated visual behaviors following neurotrophic rescue of axotomized neurons in medial frontal cortex. J Neurosci 13:614-22 |
| Eagleson, K L; Cunningham, T J; Haun, F (1992) Rescue of both rapidly and slowly degenerating neurons in the dorsal lateral geniculate nucleus of adult rats by a cortically derived neuron survival factor. Exp Neurol 116:156-62 |
