PMID- 12111797 OWN - NLM STAT- MEDLINE DCOM- 20020814 LR - 20061115 IS - 0360-4012 (Print) IS - 0360-4012 (Linking) VI - 69 IP - 2 DP - 2002 Jul 15 TI - Brain-derived neurotrophic factor applied to the motor cortex promotes sprouting of corticospinal fibers but not regeneration into a peripheral nerve transplant. PG - 160-8 AB - Previous experiments from our laboratory have shown that application of brain-derived neurotrophic factor (BDNF) to the red nucleus or the motor cortex stimulates an increase in the expression of regeneration-associated genes in rubrospinal and corticospinal neurons. Furthermore, we have previously shown that BDNF application stimulates regeneration of rubrospinal axons into a peripheral graft after a thoracic injury. The current study investigates whether application of BDNF to the motor cortex will facilitate regeneration of corticospinal neurons into a peripheral nerve graft placed into the thoracic spinal cord. In adult Sprague Dawley rats, the dorsal columns and the corticospinal tract between T9 and T10 were ablated by suction, and a 5-mm-long segment of predegenerated tibial nerve was autograft implanted into the lesion. With an osmotic pump, BDNF was infused directly into the parenchyma of the motor cortex for 14 days. Growth of the corticospinal tract into the nerve graft was then evaluated by transport of an anterograde tracer. Anterogradely labeled corticospinal fibers were not observed in the peripheral nerve graft in animals treated with saline or BDNF. Serotinergic and noradrenergic fibers, as well as peripheral sensory afferents, were observed to penetrate the graft, indicating the viability of the peripheral nerve graft as a permissive growth substrate for these specific fiber types. Although treatment of the corticospinal fibers with BDNF failed to produce regeneration into the graft, there was a distinct increase in the number of axonal sprouts rostral to the injury site. This indicates that treatment of corticospinal neurons with neurotrophins, e.g., BDNF, can be used to enhance sprouting of corticospinal axons within the spinal cord. Whether such sprouting leads to functional recovery after spinal cord injury is currently under investigation. CI - Copyright 2002 Wiley-Liss, Inc. FAU - Hiebert, G W AU - Hiebert GW AD - CORD (Collaboration On Repair Discoveries), University of British Columbia, Vancouver, British Columbia, Canada. hiebert@cord.ubc.ca FAU - Khodarahmi, K AU - Khodarahmi K FAU - McGraw, J AU - McGraw J FAU - Steeves, J D AU - Steeves JD FAU - Tetzlaff, W AU - Tetzlaff W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci Res JT - Journal of neuroscience research JID - 7600111 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology/*physiology MH - Immunohistochemistry MH - Male MH - Motor Cortex/*drug effects MH - Nerve Regeneration/*drug effects MH - Peripheral Nerves/*drug effects MH - Pyramidal Tracts/drug effects/*growth & development MH - Rats MH - Rats, Sprague-Dawley MH - Transplants EDAT- 2002/07/12 10:00 MHDA- 2002/08/15 10:01 CRDT- 2002/07/12 10:00 PHST- 2002/07/12 10:00 [pubmed] PHST- 2002/08/15 10:01 [medline] PHST- 2002/07/12 10:00 [entrez] AID - 10.1002/jnr.10275 [doi] PST - ppublish SO - J Neurosci Res. 2002 Jul 15;69(2):160-8. doi: 10.1002/jnr.10275.