The long-range goals of the experiments described in this application are to understand the anatomical and molecular underpinnings which determine the accuracy of peripheral nerve regeneration. The present proposal addresses accuracy of peripheral nerve regeneration at the nerve trunk level, within the context of """"""""preferential motor reinnervation"""""""". Preferential motor reinnervation (PMR) refers to the fact that during regeneration of rat femoral nerve, a mixed peripheral nerve, motor axons have been shown to preferentially, albeit incompletely, reinnervate a terminal motor vs sensory distal nerve branch. Our preliminary studies have lead to two major discoveries that shape our proposed experiments: 1) the addition of growth factors to the nerve repair site significantly enhances PR; and 2) BDNF mRNA levels are differentially regulated in the terminal motor and sensory nerve trunks following femoral nerve transection. This proposal has three main parts. The first will be to determine, on an in vivo level, the mechanism by which the addition of specific growth factors to a nerve transection site increase preferential motor reinnervation. The second part will determine if PMR is dependent upon the presence of living Schwann cells. Finally, we will analyze the potential involvement of the neurotrophins and ciliary neuronotrophic factor, and we will use uniquely powerful molecular techniques to demonstrate differentially expressed gene products that may underlie the accuracy of regeneration in this model system. Gaining insight into the cellular and molecular underpinnings which determine the accuracy of nerve regeneration in these animal models has direct relevance to human peripheral nerve repair.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS022404-10A1
Application #
2264497
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1986-04-01
Project End
1998-05-31
Budget Start
1995-07-01
Budget End
1996-05-31
Support Year
10
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Duke University
Department
Surgery
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Krarup, Christian; Archibald, Simon J; Madison, Roger D (2002) Factors that influence peripheral nerve regeneration: an electrophysiological study of the monkey median nerve. Ann Neurol 51:69-81
Madison, R D; Zomorodi, A; Robinson, G A (2000) Netrin-1 and peripheral nerve regeneration in the adult rat. Exp Neurol 161:563-70
Robinson, G A; Madison, R D (2000) Survival of adult rat retinal ganglion cells with regrown axons in peripheral nerve grafts: a comparison of graft attachment with suture of fibrin glue. J Neurosurg 93:275-8
Madison, R D; Robinson, G A (1998) lambda RNA internal standards quantify sensitivity and amplification efficiency of mammalian gene expression profiling. Biotechniques 25:504-8, 510, 512, passim
Madison, R D; Archibald, S J; Brushart, T M (1996) Reinnervation accuracy of the rat femoral nerve by motor and sensory neurons. J Neurosci 16:5698-703
Archibald, S J; Shefner, J; Krarup, C et al. (1995) Monkey median nerve repaired by nerve graft or collagen nerve guide tube. J Neurosci 15:4109-23
Madison, R D; Archibald, S J (1994) Point sources of Schwann cells result in growth into a nerve entubulation repair site in the absence of axons: effects of freeze-thawing. Exp Neurol 128:266-75
Madison, R D; Macklis, J D (1993) Noninvasively induced degeneration of neocortical pyramidal neurons in vivo: selective targeting by laser activation of retrogradely transported photolytic chromophore. Exp Neurol 121:153-9
Paramore, C G; Turner, D A; Madison, R D (1993) Induction of neuronal morphology in adrenal chromaffin cells cocultured with denervated Schwann cells. Exp Neurol 121:288-94
Harsh, C; Archibald, S J; Madison, R D (1991) Double-labeling of saphenous nerve neuron pools: a model for determining the accuracy of axon regeneration at the single neuron level. J Neurosci Methods 39:123-30

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