NT-3 delivered by an adenoviral vector induces injured dorsal root axons to regenerate into the spinal cord of adult rats

TY - JOUR

T1 - NT-3 delivered by an adenoviral vector induces injured dorsal root axons to regenerate into the spinal cord of adult rats

AU - Zhang, Y

AU - Dijkhuizen, Paul A

AU - Anderson, Patrick N

AU - Lieberman, A Robert

AU - Verhaagen, J

PY - 1998/11/15

Y1 - 1998/11/15

N2 - Sensory axons interrupted in the dorsal roots of adult mammals are normally unable to regenerate into the spinal cord. We have investigated whether the introduction of a neurotrophin gene into the spinal cord might offer an approach to otherwise intractable spinal root injuries. The dorsal roots of the 4th, 5th, and 6th lumbar spinal nerves of adult rats were severed and reanastomosed. Fourteen to nineteen days later, adenoviral vectors containing either the LacZ or NT-3 genes were injected into the ventral horn of the lumbar spinal cord, resulting in strong expression of the transgenes in glial cells and motor neurons between 4 and 40 days after injection. When dorsal root axons were transganglionically labelled with HRP conjugated to cholera toxin subunit B, 16 to 37 days after dorsal root injury, large numbers of labelled axons could be seen to have regenerated into the cord, but only in those animals injected with vector carrying the NT-3 gene. The regenerated axons were found at the injection site, mainly in the grey matter, and had penetrated as deep as lamina V. Gene therapy with adenoviral vectors encoding a neurotrophin has therefore been shown to be capable of enhancing and directing the regeneration of a subpopulation of dorsal root axons (probably myelinated A fibres), into and through the CNS environment.

AB - Sensory axons interrupted in the dorsal roots of adult mammals are normally unable to regenerate into the spinal cord. We have investigated whether the introduction of a neurotrophin gene into the spinal cord might offer an approach to otherwise intractable spinal root injuries. The dorsal roots of the 4th, 5th, and 6th lumbar spinal nerves of adult rats were severed and reanastomosed. Fourteen to nineteen days later, adenoviral vectors containing either the LacZ or NT-3 genes were injected into the ventral horn of the lumbar spinal cord, resulting in strong expression of the transgenes in glial cells and motor neurons between 4 and 40 days after injection. When dorsal root axons were transganglionically labelled with HRP conjugated to cholera toxin subunit B, 16 to 37 days after dorsal root injury, large numbers of labelled axons could be seen to have regenerated into the cord, but only in those animals injected with vector carrying the NT-3 gene. The regenerated axons were found at the injection site, mainly in the grey matter, and had penetrated as deep as lamina V. Gene therapy with adenoviral vectors encoding a neurotrophin has therefore been shown to be capable of enhancing and directing the regeneration of a subpopulation of dorsal root axons (probably myelinated A fibres), into and through the CNS environment.

KW - Adenoviridae

KW - Animals

KW - Axons

KW - Cell Movement

KW - Female

KW - Genetic Therapy

KW - Genetic Vectors

KW - In Situ Hybridization

KW - Injections, Spinal

KW - Motor Neurons

KW - Nerve Growth Factors

KW - Nerve Regeneration

KW - Neuroglia

KW - Neurotrophin 3

KW - Rats

KW - Rats, Sprague-Dawley

KW - Sciatic Nerve

KW - Spinal Cord Injuries

KW - Spinal Nerve Roots

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/(SICI)1097-4547(19981115)54:4<554::AID-JNR12>3.0.CO;2-M

DO - 10.1002/(SICI)1097-4547(19981115)54:4<554::AID-JNR12>3.0.CO;2-M

M3 - Article

C2 - 9822165

SN - 0360-4012

VL - 54

SP - 554

EP - 562

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

IS - 4

ER -