Following trauma to the CNS a regenerative process known as axon sprouting or reactive synaptogenesis begins. In this way the circuitry of the damaged area is reordered, resulting in functional changes. The aged CNS has a diminished injury-induced growth response when compared to young adults. The proposed experiments will determine the mechanism(s) behind the aged brain's response to damage. In the first set of experiments we will assess the ability of the aged animal to support reactive growth in two different areas of the CNS, the hippocampus and septum. Both areas are denervated by a transection of the fimbria-fornix. This will explore the extent of the growth reponse in the aged brain. The second set of experiments will determine if experimental alteration in the neuropil milieu can directly influence the altered lesion-induced growth response in the aged brain. Following injury in the young adult, a timed accumulation of a trophic substance, neuronotrophic factor (NTF), is produced which supports cell survival and promotes process growth. By administering a purified form of NTF we will test its ability to promote lesion-induced growth in the aged brain. In the third series of investigations, fetal tissue will be implanted into the aged host to determine if the alteration of plasticity in the senescent brain is the loss of the aged neuron's ability to innervate a target area or the loss of the target area to support reinnervation. By providing a detaileds qualitative and quantitative analysis of the restoration process at various times post surgical intervention, it will be possible to gain information on the rate and magnitude of the reactive growth response. Quantitative electron microscopic and biochemical indices of lesion-induced growth will be employed.
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