PMID- 11077420 OWN - NLM STAT- MEDLINE DCOM- 20010104 LR - 20190906 IS - 0021-9967 (Print) IS - 0021-9967 (Linking) VI - 428 IP - 4 DP - 2000 Dec 25 TI - BDNF abolishes the survival effect of NT-3 in axotomized Clarke neurons of adult rats. PG - 671-80 AB - Neurotrophin-3 (NT-3) and brain-derived neurotrophic factor (BDNF) have previously been shown to support survival and axonal regeneration in various types of neurons. Also, synergistic neuroprotective effects of these neurotrophins have been reported in descending rubrospinal neurons after cervical spinal cord injury (Novikova et al., [2000] Eur. J. Neurosci. 12:776-780). The present study investigates the effects of intrathecally delivered NT-3 and BDNF on the survival and atrophy of ascending spinocerebellar neurons of Clarke nucleus (CN) after cervical spinal cord injury in adult rats. At 8 weeks after cervical spinal cord hemisection, 40% of the axotomized CN neurons had been lost, and the remaining cells exhibited marked atrophy. Microglial activity was significantly increased in CN of the operated side. Intrathecal infusion of NT-3 for 8 weeks postoperatively resulted in 91% cell survival and a reduction in cell atrophy, but did not reduce microglial activity. In spite of the fact that the CN neurons expressed both TrkC and TrkB receptors, only NT-3 had a neuroprotective effect, whereas BDNF was ineffective. Furthermore, when a combination of BDNF and NT-3 was administered, the neuroprotective effect of NT-3 was lost. The present results indicate a therapeutic potential for NT-3 in the treatment of spinal cord injury, but also demonstrate that in certain neuronal populations the neuroprotection obtained by a combination of neurotrophic factors may be less than that of a single neurotrophin. CI - Copyright 2000 Wiley-Liss, Inc. FAU - Novikova, L N AU - Novikova LN AD - Department of Integrative Medical Biology, Section for Anatomy, Umea University, SE-901 87 Umea, Sweden. FAU - Novikov, L N AU - Novikov LN FAU - Kellerth, J O AU - Kellerth JO LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Comp Neurol JT - The Journal of comparative neurology JID - 0406041 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Neurotrophin 3) RN - EC 1.14.13.39 (Nitric Oxide Synthase) SB - IM MH - Animals MH - Axotomy/*adverse effects MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cell Survival/*drug effects/physiology MH - Cerebellum/drug effects/pathology/physiopathology MH - Drug Interactions/*physiology MH - Female MH - Microglia/cytology/physiology MH - Neural Pathways/drug effects/pathology/physiopathology MH - Neuroprotective Agents/pharmacology MH - Neurotrophin 3/*pharmacology MH - Nitric Oxide Synthase/metabolism MH - Rats/anatomy & histology/*metabolism MH - Rats, Sprague-Dawley MH - Retrograde Degeneration/*drug therapy/pathology/physiopathology MH - Spinal Cord/drug effects/pathology/physiopathology MH - Spinal Cord Injuries/*drug therapy/pathology/physiopathology EDAT- 2000/11/15 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/11/15 11:00 PHST- 2000/11/15 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/11/15 11:00 [entrez] AID - 10.1002/1096-9861(20001225)428:4<671::AID-CNE7>3.0.CO;2-H [pii] AID - 10.1002/1096-9861(20001225)428:4<671::aid-cne7>3.0.co;2-h [doi] PST - ppublish SO - J Comp Neurol. 2000 Dec 25;428(4):671-80. doi: 10.1002/1096-9861(20001225)428:4<671::aid-cne7>3.0.co;2-h.