Abstract
We have recently reported that rats with complete thoracic spinal cord injury (SCI) that received a combinatorial treatment, including viral brain-derived neurotrophic factor (BDNF) delivery in the spinal cord, not only showed enhanced axonal regeneration, but also deterioration of hind-limb motor function. By demonstrating that BDNF over-expression can trigger spasticity-like symptoms in a rat model of sacral SCI, we proposed a causal relationship between the observed spasticity-like symptoms (i.e., resistance to passive range of motion) and the over-expression of BDNF. The current study was originally designed to evaluate a comparable combined treatment for cervical SCI in the rat to improve motor recovery. Once again we found similar signs of spasticity involving clenching of the paws and wrist flexion. This finding changed the focus of the study and, we then explored whether this spasticity-like symptom is directly related to the over-expression of BDNF by administering a BDNF antagonist. Using electromyographic measurements we showed that this treatment gradually diminished the resistance to overcome forelimb flexion in an acute experiment. Thus, we conclude that neuro-excitatory effects of chronic BDNF delivery together with diminished descending control after SCI can result in adverse effects.
Highlights
Axonal regeneration in the adult mammalian central nervous system is inhibited by numerous factors [1] impeding the development of effective treatments for brain or spinal cord injuries (SCI)
By 6 weeks, only 12% of rats (2 out of 16) in the control treatment group showed abnormal wrist flexion and clenching of the paw. This stood in contrast to 60% (3 out of 5) of rats that were injected with Self-complementary adeno-associated viral vectors (scAAV)-brain-derived neurotrophic factor (BDNF) and 72% (13 out of 18) of rats belonging to the FULL treatment group and three out of seven rats (43%) in the GRAFT/NT-3 group which received the cell grafts expressing BDNF and NT-3 in the lesion site and scAAVNT-3 only expression caudal to lesion
Rats in all groups attempted to reach for pellets, a significant decline in the attempt rate was apparent in the treated groups when compared to their baseline attempt rate measurements (FULL treatment group: 15.4%, scAAV-BDNF group: 35%, GRAFT/NT-3 group: 56.7%; GRAFT/ChABC group: 25.7%, and control group: 86.7%)
Summary
Axonal regeneration in the adult mammalian central nervous system is inhibited by numerous factors [1] impeding the development of effective treatments for brain or spinal cord injuries (SCI). It is likely that repair of the injured spinal cord by axonal regeneration and plasticity will require a combined treatment approach. Provide an indirect explanation by demonstrating that the over-expression of BDNF could promote the development of hyperreflexia in tail muscles in a sacral model of SCI [11] It remains unclear whether this effect of BDNF was caused by its neuro-excitatory properties or through an augmentation of neuroplasticity and/or regenerative growth. The focus of the analysis shifted when severe spasticity-like symptoms in the injured forelimb became evident, which led us to focus on determining the cause of spasticity To address this question we administered a BDNF antagonist into the spinal cord of rats that showed spasticity-like symptoms, and these were gradually reduced by this treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
