PMID- 17652412 OWN - NLM STAT- MEDLINE DCOM- 20080108 LR - 20131121 IS - 0022-3077 (Print) IS - 0022-3077 (Linking) VI - 98 IP - 4 DP - 2007 Oct TI - Neurotrophic factors promote and enhance locomotor recovery in untrained spinalized cats. PG - 1988-96 AB - In spinal cats, locomotor recovery without rehabilitation is limited, but weight-bearing stepping returns with treadmill training. We studied whether neurotrophins administered to the injury site also restores locomotion in untrained spinal cats and whether combining both neurotrophins and training further improves recovery. Ordinary rat fibroblasts or a mixture of fibroblasts secreting brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) (Fb-NTF) were grafted into T12 spinal transection sites. Cats with each type of transplant were divided into two groups: one receiving daily training and the other receiving no training. As expected, trained cats with/without neurotrophin-producing transplants could step on the treadmill. Untrained cats without neurotrophin-producing transplants could not locomote. However, untrained cats with neurotrophin-secreting transplants performed plantar weight-bearing stepping at speeds up to 0.8 m/s as early as 2 wk after transection. Locomotor capability and stance lengths in these animals were similar to those in animals receiving training alone, suggesting that administration of BDNF/NT-3 was equivalent to treadmill training in restoring locomotion in chronically spinalized cats. Cats receiving both interventions showed the greatest improvement in step length. Anatomical evaluation indicated that all transections were complete and that axons did not enter the cord caudal to the graft. Thus BDNF/NT-3 secreting fibroblasts were equivalent to training in their ability to engage the locomotor circuitry in chronic spinal cats. Furthermore, the rapid time-course of recovery and the absence of axonal growth through the transplants indicate that the restorative mechanisms were not related to supraspinal axonal growth. Finally, the results show that transplants beneficial in rodents are applicable to larger mammals. FAU - Boyce, Vanessa S AU - Boyce VS AD - Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA. FAU - Tumolo, Maureen AU - Tumolo M FAU - Fischer, Itzhak AU - Fischer I FAU - Murray, Marion AU - Murray M FAU - Lemay, Michel A AU - Lemay MA LA - eng GR - NS24707/NS/NINDS NIH HHS/United States GR - NS41975/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20070725 PL - United States TA - J Neurophysiol JT - Journal of neurophysiology JID - 0375404 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) SB - IM CIN - J Neurophysiol. 2007 Oct;98(4):1845-6. PMID: 17686909 MH - Animals MH - Biomechanical Phenomena MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Cats MH - Data Interpretation, Statistical MH - Decerebrate State/*drug therapy/*physiopathology/therapy MH - Exercise Therapy MH - Female MH - Fibroblasts/drug effects/transplantation MH - Functional Laterality/physiology MH - Hindlimb/physiology MH - Immunohistochemistry MH - Locomotion/*physiology MH - Nerve Growth Factors/*pharmacology MH - Neuronal Plasticity/drug effects/physiology MH - Neurotrophin 3/pharmacology MH - Spinal Cord/cytology EDAT- 2007/07/27 09:00 MHDA- 2008/01/09 09:00 CRDT- 2007/07/27 09:00 PHST- 2007/07/27 09:00 [pubmed] PHST- 2008/01/09 09:00 [medline] PHST- 2007/07/27 09:00 [entrez] AID - 00391.2007 [pii] AID - 10.1152/jn.00391.2007 [doi] PST - ppublish SO - J Neurophysiol. 2007 Oct;98(4):1988-96. doi: 10.1152/jn.00391.2007. Epub 2007 Jul 25.