A TrkB Antibody Agonist Promotes Plasticity after Cervical Spinal Cord Injury in Adult Rats.
After spinal cord injury (SCI) in mammals, there is only limited repair and, consequently, only moderate recovery. One mechanism frequently discussed to be involved in this recovery is plasticity (i.e., adaptations in spared neuronal circuitries). In the current study, we tested the effect of an intrathecal application of the TrkB agonist antibody, 29D7, on plasticity after cervical SCI in adult rats. Treatment with 29D7 for 4 weeks resulted in an ∼50% increase in collateral sprouting of severed corticospinal tract fibers above the lesion compared to the control group and enhanced branching in the gray matter rostral to the injury. Growth-associated protein 43 immunoreactivity in the spinal cord rostral to the level of the injury as well as contralateral to the lesion was also increased. These indications of enhanced plasticity by 29D7 were paralleled by improved performances of the mildly affected paw, as assessed by Montoya and tray reaching tasks. The reaching behaviors of the paw ipsilateral to the side of severe injury to the cortico- and rubrospinal tract were not altered by the treatment. The present study suggests that 29D7 may be a potential candidate to promote plasticity and functional recovery, especially after moderate SCI. Future studies confirming these results, along with a potential combinatory therapy including rehabilitative training, will be needed to evaluate the clinical value of such a treatment.
Fouad
Karim
K
Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada.
Vavrek
Romana
R
Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada.
Cho
Seongeun
S
Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Alberta, Canada.|U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D066193:Cervical Cord / Q000187:drug effects / Q000293:injuries* / Q000502:physiology; D005260:Female; D007260:Infusion Pumps; D007278:Injections, Spinal; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D020813:Receptor, trkB / Q000819:agonists*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology
D000911:Antibodies, Monoclonal; C000621230:Ntrk2 protein, rat; D020813:Receptor, trkB