The long term objectives of this research are to test, in vivo, the influence of the microenvironment on axonal regeneration in the mouse peripheral nervous system. We will continue to develop anatomic and physiologic methods and techniques which will quantitatively assess functional as well as anatomical recovery following peripheral nerve repair.
Specific Aims I and II will quantify the regeneration response of sensory and motor neurons and their axons. This quantification will be carried out for different experimental conditions which systematically alter the microenvironment of the regenerating axons.
Specific Aims III -V focus on interactions of the regenerated axons with their target. The goal of these experiments is to establish how many axons grow back to their appropriate targets, and once in the target how many of them establish anatomical and physiological connections which are functional.
Specific Aim V I will use the quantitative methods of the previous specific aims to directly compare the efficacy of various standard procedures for peripheral nerve repair. The results of these studies will provide quantitative baseline data concerning functional recovery following peripheral nerve repair. Direct correlation of anatomical and physiological measures of functional nerve regeneration will be used to compare the efficacy of different peripheral nerve repair strategies. Such quantitative comparisons have direct clinical relevance to human peripheral nerve repair.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurological Sciences Subcommittee 1 (NLS)
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Duke University
Schools of Medicine
United States
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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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