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AXONAL GROWTH AND GUIDANCE FOR NERVOUS SYSTEM REPAIR

Award Number: R01NS040592
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/27/2000
PERIOD OF PERFORMANCE END DATE: 12/31/2009

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AXONAL GROWTH AND GUIDANCE FOR NERVOUS SYSTEM REPAIR - DESCRIPTION (provided by applicant): Over 50,000 peripheral nerve repair procedures are performed a year due to injury (National Center for Health Statistics, 1995). These data do not include nerve injury due to tumor resection or prostatectomies. Even though the peripheral nerves regenerate well, only 10 to 20% of patients that undergo surgery to repair traumatic nerve injuries show excellent to very good recovery of function. The high incidence of failed recovery is due to the misrouting of regenerating axons to their targets. This proposal is designed to better understand the potential mechanisms that direct this growth to increase functional recovery in adults. The studies will examine the role strategically expressed neurotrophins and chemorepulsive factors will have on directing the growth of sensory and motor axons into appropriate nerve branches or the spinal cord. All the experiments in this proposal will use bioreabsorbable implants to induce nerve repair and targeted gene expression of guidance factors. The first aim of these experiments will explore the use of the neurotrophins GDNF, BDNF, and NT-3 to induce the regeneration of sensory axon subsets across a 6mm dorsal root lesion gap and into the spinal cord. Behavioral analysis will examine recovery of mechanoreceptive and proprioceptive responses. The second to forth aim of experiments will use the femoral nerve model to examine peripheral nerve targeting after large excision lesions to that nerve. The femoral nerve contains both sensory and motor axons that normally segregate into a sensory branch (saphenous) and a motor branch (quadriceps femoris). After cut injury, regeneration is mostly random, in which each branch will contain a mixture of both cutanteous sensory and motor axons. The second aim will be to guide sensory axons into the saphenous branch and not the motor branch. In this study, selective neurotrophins that are growth attractive for sensory axons will be expressed in the saphenous nerve and repulsive factors that are specifically inhibitory to sensory axons expressed in the motor branch. The third aim will examine neurotrophins and repulsive factors for the selective guidance of regenerating motor and proprioceptive axons into the motor branch and not the saphenous nerve. The forth aim is designed to incorporate the factors from aim 2 and 3 to optimize target directed regeneration to more normal like patterns. This aim will also develop and test clinically relevant bioreabsorbable nerve cuffs for slow release of guidance factors. This grant proposal is designed to better define the molecular mechanisms that influence axonal regeneration and guidance within the adult PNS, with the ultimate goal of directing and organizing regeneration to more appropriate targets, while discouraging aberrant connections.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2009 ( Subtotal = $291,333 )
2009	2009	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	11/27/2008	NON-COMPETING CONTINUATION	$262,199
2009	2009	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	4/7/2009	NON-COMPETING CONTINUATION	$29,134
														Subtotal = $291,333

Issue Date FY: 2008 ( Subtotal = $291,333 )
2008	2008	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	12/18/2007	NON-COMPETING CONTINUATION	$291,333
														Subtotal = $291,333

Issue Date FY: 2007 ( Subtotal = $291,178 )
2007	2007	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	1/22/2007	NON-COMPETING CONTINUATION	$291,178
														Subtotal = $291,178

Issue Date FY: 2006 ( Subtotal = $299,715 )
2006	2006	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	12/15/2005	NON-COMPETING CONTINUATION	$299,715
														Subtotal = $299,715

Issue Date FY: 2005 ( Subtotal = $318,567 )
2005	2005	UNIVERSITY OF KENTUCKY, RESEARCH FOUNDATION	105 KINKEAD HALL	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/7/2004	COMPETING CONTINUATION	$318,567
														Subtotal = $318,567

Issue Date FY: 2003 ( Subtotal = $302,351 )
2003	2003	UNIVERSITY OF KENTUCKY	337 PETERSON SERVICE BUILDING	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4		NON-COMPETING CONTINUATION	$302,351
														Subtotal = $302,351

Issue Date FY: 2002 ( Subtotal = $293,543 )
2002	2002	UNIVERSITY OF KENTUCKY	337 PETERSON SERVICE BUILDING	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/29/2002	NON-COMPETING CONTINUATION	$293,543
														Subtotal = $293,543

Issue Date FY: 2001 ( Subtotal = $285,240 )
2001	2001	UNIVERSITY OF KENTUCKY	337 PETERSON SERVICE BUILDING	LEXINGTON	KY	40506	FAYETTE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/7/2001	NON-COMPETING CONTINUATION	$285,240
														Subtotal = $285,240

Issue Date FY: 2000 ( Subtotal = $288,483 )
2000	2000	UNIVERSITY OF KENTUCKY	337 PETERSON SERVICE BUILDING	LEXINGTON	KY	40506	FAYETTE	USA	Biological Basis Research in the Neurosciences	000	1	3/22/2000	NEW	$288,483
														Subtotal = $288,483

Grand Total All Awards = $2,661,743

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AXONAL GROWTH AND GUIDANCE FOR NERVOUS SYSTEM REPAIR

Award Number: R01NS040592

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/27/2000

PERIOD OF PERFORMANCE END DATE: 12/31/2009

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