Long-term viral brain-derived neurotrophic factor delivery promotes spasticity in rats with a cervical spinal cord hemisection.
Fouad K, Bennett DJ, Vavrek R, Blesch A.
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.