PMID- 12353221
OWN - NLM
STAT- MEDLINE
DCOM- 20021030
LR  - 20061115
IS  - 0021-9967 (Print)
IS  - 0021-9967 (Linking)
VI  - 452
IP  - 3
DP  - 2002 Oct 21
TI  - Differential effects of neurotrophins on neuronal survival and axonal 
      regeneration after spinal cord injury in adult rats.
PG  - 255-63
AB  - Spinal cord injury (SCI) induces retrograde cell death in descending pathways, 
      which can be prevented by long-term intrathecal infusion of neurotrophins 
      (Novikova et al. [2000] Eur J Neurosci 12:776-780). The present study 
      investigates whether the same treatment also leads to improved regeneration of 
      the injured tracts. After cervical SCI in adult rats, a peripheral nerve graft 
      was attached to the rostral wall of the lesion cavity. The animals were treated 
      by local application into the cavity of Gelfoam soaked in (1) phosphate buffered 
      saline (untreated controls) or (2) a mixture of the neurotrophins brain-derived 
      neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) (local treatment), or by 
      intrathecal infusion of BDNF + NT-3 for (3) 2 weeks (short-term treatment) or (4) 
      5-8 weeks (long-term treatment). Despite a very strong survival effect, long-term 
      treatment failed to stimulate ingrowth of descending tracts into the nerve graft. 
      In comparison with untreated controls, the latter treatment also caused 35% 
      reduction in axonal sprouting of descending pathways rostral to the lesion site 
      and 72% reduction in the number of spinal cord neurons extending axons into the 
      nerve graft. Local and short-term treatments neither prevented retrograde cell 
      death nor enhanced regeneration of descending tracts, but induced robust 
      regeneration of spinal cord neurons into the nerve graft. These results indicate 
      that the signal pathways promoting neuronal survival and axonal regeneration, 
      respectively, in descending tracts after SCI respond differently to neurotrophic 
      stimuli and that efficient rescue of axotomized tract neurons is not a sufficient 
      prerequisite for regeneration.
CI  - Copyright 2002 Wiley-Liss, Inc.
FAU - Novikova, Liudmila N
AU  - Novikova LN
AD  - Department of Integrative Medical Biology, Section of Anatomy, Umea University, 
      SE-901 87 Umea, Sweden.
FAU - Novikov, Lev N
AU  - Novikov LN
FAU - Kellerth, Jan-Olof
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 (Neurotrophin 3)
SB  - IM
MH  - Animals
MH  - Axons/drug effects
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Survival/*drug effects
MH  - Cervical Vertebrae/pathology
MH  - Female
MH  - Nerve Degeneration/drug therapy/pathology
MH  - Nerve Regeneration/*drug effects
MH  - Neurotrophin 3/*pharmacology
MH  - Peroneal Nerve/transplantation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Spinal Cord Injuries/*drug therapy/pathology/*physiopathology/surgery
MH  - Time Factors
MH  - Transplantation, Autologous
EDAT- 2002/09/28 04:00
MHDA- 2002/11/01 04:00
CRDT- 2002/09/28 04:00
PHST- 2002/09/28 04:00 [pubmed]
PHST- 2002/11/01 04:00 [medline]
PHST- 2002/09/28 04:00 [entrez]
AID - 10.1002/cne.10381 [doi]
PST - ppublish
SO  - J Comp Neurol. 2002 Oct 21;452(3):255-63. doi: 10.1002/cne.10381.