An investigation into the potential for activity-dependent regeneration of the rubrospinal tract after spinal cord injury.
We tested whether regeneration of transected rubrospinal tract (RST) axons is facilitated by a prolonged electrical stimulation of these axons. A peripheral nerve was grafted to the transected RST at the cervical level (C4/5) of adult rats, providing a permissive environment for regeneration of rubrospinal axons. Direct antidromic stimulation of the RST was applied immediately after grafting through a microwire inserted just rostral to the RST lesion, using a 1-h 20-Hz supramaximal stimulation protocol. Stimulation caused no direct damage to rubrospinal axons, and was sufficient to recruit the entire rubrospinal tract. In control animals that had a nerve graft and implanted microwire with no stimulation, there were 42.7 +/- 10.2 rubrospinal neurons regenerated into the graft at 8 weeks, as assessed by retrograde labelling. In test animals that were stimulated there were 28.2 +/- 7.4 back-labelled neurons, not significantly different from control, indicating that this stimulation did not improve the regenerative capacity of rubrospinal neurons. Furthermore, reverse-transcriptase polymerase chain reaction and in situ hybridization for brain-derived neurotrophic factor (BDNF) and/or growth-associated protein-43 (GAP-43) expression in rubrospinal neurons revealed no significant difference between stimulated and unstimulated groups at 48 h after injury, with either 1 or 8 h of stimulation. In summary, direct stimulation of the injured RST axons for the periods tested does not increase expression of GAP-43 and BDNF, and ultimately does not promote regeneration of these central nervous system axons.
Harvey
Philip J
PJ
Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.
Grochmal
Joey
J
Tetzlaff
Wolfram
W
Gordon
Tessa
T
Bennett
David J
DJ
D000818:Animals; D019771:Axotomy / Q000379:methods; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000502:physiology* / Q000528:radiation effects; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D019922:GAP-43 Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D017403:In Situ Hybridization / Q000379:methods; D008872:Microwaves / Q000627:therapeutic use; D009416:Nerve Regeneration / Q000502:physiology*; D009474:Neurons / Q000528:radiation effects; D010525:Peripheral Nerves / Q000637:transplantation; D011712:Pyramidal Tracts / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012012:Red Nucleus / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013119:Spinal Cord Injuries / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy
D019208:Brain-Derived Neurotrophic Factor; D019922:GAP-43 Protein; D012333:RNA, Messenger