Transplantation of Genetically Modified Fibroblasts Expressing BDNF in Adult Rats with a Subtotal Hemisection Improves Specific Motor and Sensory Functions

Abstract

Objective: We have previously reported that grafting fibroblasts genetically mod ified to express brain-derived neurotrophic factor (BDNF) into a subtotal cervical hemisection site that destroys the entire lateral funiculus will promote regeneration of rubrospinal axons and growth of other axons, prevent atrophy and death of axo tomized red nucleus neurons, and improve forelimb use during spontaneous vertical exploration. We have now extended these studies by using additional sensorimotor tests to examine recovery. Methods: The range of tests used included those in which the intervention did not improve recovery, those in which the intervention was as sociated with recovery, and those that showed little deficit. The selected tasks tested both sensory and motor functions and both forelimb and forelimb function. We used the open-field locomotor rating scale (BBB), locomotion on a narrow beam, forelimb use during swimming, horizontal rope walking, and a somatosensory asymmetry (patch- removal) test. After testing during an 8-week recovery period, a second lesion was made just rostral to the initial lesion/transplant site to test the role of the transplant in recovery. The rats were then retested for a further 5 weeks after the repeated le sion. Results: The horizontal rope, swim, and patch-removal tests were reliably sen sitive to the subtotal hemisection injury. Fb/BDNF-transplanted animals recovered motor functions on the horizontal rope-crossing test, and this recovery was abolished by a second lesion just rostral to the first lesion/transplant. In the patch-removal test, the latency to contact the affected limb was shorter in Fb/BDNF-treated rats than in the control group, and this effect was completely abolished by a second lesion. Con clusions : The rope-crossing and patch-removal tests are particularly useful tasks for assessing the beneficial effects of BDNF-expressing grafts in this injury model. Key Words: BDNF—Fibroblasts—Transplants—Recovery of function.