title: Dorsal column sensory axons lack TrkC and are not rescued by local neurotrophin-3 infusions following spinal cord contusion in adult rats.
abstract: By reducing the progressive degeneration and disconnection of axons following spinal cord injury the functional outcome should improve. After direct transection of dorsal column sensory axons, neurotrophin-3 (NT-3) treatment can reduce degeneration and promote regeneration of the proximal stumps. Here, we tested in adult rats whether NT-3 infusion at the site of a moderate T9 spinal cord contusion would rescue sensory connections to the gracile nucleus in the medulla. Sensory projections were anterogradely traced bilaterally with injections of cholera toxin B (CTB) into the sciatic nerve 3 days before analysis. Seven days after the contusion plus intrathecal (subarachnoid) vehicle infusion as a control, the CTB-positive innervation of the gracile nucleus was reduced to approximately 25% of sham-operated rats. Intrathecal infusion of 10 microg/day of NT-3 did not affect this reduced innervation. To ensure good tissue penetration and high concentrations of NT-3 early after the injury, other rats received intraparenchymal infusions of vehicle or NT-3 near the injury site starting 2 days before until 7 days after the injury. This NT-3 treatment also did not affect the reduced innervation. This suggests that local NT-3 treatments cannot protect sensory axons from secondary degeneration after a contusive spinal cord injury. These results are likely because TrkC is not present in axons of the dorsal columns or gracile nucleus, or in other dorsal column cell types, even after the contusion. Together with published results, our data suggest that NT-3 is a peripherally--but not centrally--derived neurotrophic factor for sensory neurons.
authors.affiliation: Kentucky Spinal Cord Injury Research Center, Department of Neurological Surgery, MDR Building, Room 616, University of Louisville, Louisville, KY 40292, USA.
authors.forename: K Adam
authors.initials: KA
authors.lastname: Baker
authors.forename: Shojiro
authors.initials: S
authors.lastname: Nakashima
authors.forename: Theo
authors.initials: T
authors.lastname: Hagg
mesh_terms: D000344:Afferent Pathways / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D002408:Catheters, Indwelling; D002772:Cholera Toxin / Q000008:administration & dosage; D003288:Contusions / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D004334:Drug Administration Schedule; D005260:Female; D008526:Medulla Oblongata / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000517:prevention & control; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D020933:Neurotrophin 3 / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020812:Receptor, trkC / Q000172:deficiency* / Q000378:metabolism; D012584:Sciatic Nerve / Q000503:physiopathology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D020933:Neurotrophin 3; D002772:Cholera Toxin; D020812:Receptor, trkC