Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury

TY - JOUR

T1 - Adeno-associated viral vector-mediated gene transfer of brain-derived neurotrophic factor reverses atrophy of rubrospinal neurons following both acute and chronic spinal cord injury

AU - Ruitenberg, Marc J

AU - Blits, Bas

AU - Dijkhuizen, Paul A

AU - te Beek, Erik T

AU - Bakker, Arne

AU - van Heerikhuize, Joop J

AU - Pool, Chris W

AU - Hermens, Wim T J M C

AU - Boer, Gerard J

AU - Verhaagen, J.

PY - 2004/3

Y1 - 2004/3

N2 - Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.

AB - Rubrospinal neurons (RSNs) undergo marked atrophy after cervical axotomy. This progressive atrophy may impair the regenerative capacity of RSNs in response to repair strategies that are targeted to promote rubrospinal tract regeneration. Here, we investigated whether we could achieve long-term rescue of RSNs from lesion-induced atrophy by adeno-associated viral (AAV) vector-mediated gene transfer of brain-derived neurotrophic factor (BDNF). We show for the first time that AAV vectors can be used for the persistent transduction of highly atrophic neurons in the red nucleus (RN) for up to 18 months after injury. Furthermore, BDNF gene transfer into the RN following spinal axotomy resulted in counteraction of atrophy in both the acute and chronic stage after injury. These novel findings demonstrate that a gene therapeutic approach can be used to reverse atrophy of lesioned CNS neurons for an extended period of time.

KW - Acute Disease

KW - Animals

KW - Atrophy

KW - Axotomy

KW - Brain-Derived Neurotrophic Factor

KW - Chronic Disease

KW - Dependovirus

KW - Disease Models, Animal

KW - Efferent Pathways

KW - Gene Transfer Techniques

KW - Genetic Vectors

KW - Male

KW - Nerve Regeneration

KW - Neurons

KW - Rats

KW - Reaction Time

KW - Receptor, trkB

KW - Red Nucleus

KW - Retrograde Degeneration

KW - Spinal Cord

KW - Spinal Cord Injuries

KW - Journal Article

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

U2 - 10.1016/j.nbd.2003.11.018

DO - 10.1016/j.nbd.2003.11.018

M3 - Article

C2 - 15006710

SN - 0969-9961

VL - 15

SP - 394

EP - 406

JO - Neurobiology of Disease

JF - Neurobiology of Disease

IS - 2

ER -