PMID- 14641648
OWN - NLM
STAT- MEDLINE
DCOM- 20040209
LR  - 20191108
IS  - 1085-9489 (Print)
IS  - 1085-9489 (Linking)
VI  - 8
IP  - 4
DP  - 2003 Dec
TI  - Experimental strategies to promote functional recovery after peripheral nerve 
      injuries.
PG  - 236-50
AB  - The capacity of Schwann cells (SCs) in the peripheral nervous system to support 
      axonal regeneration, in contrast to the oligodendrocytes in the central nervous 
      system, has led to the misconception that peripheral nerve regeneration always 
      restores function. Here, we consider how prolonged periods of time that injured 
      neurons remain without targets during axonal regeneration (chronic axotomy) and 
      that SCs in the distal nerve stumps remain chronically denervated (chronic 
      denervation) progressively reduce the number of motoneurons that regenerate their 
      axons. We demonstrate the effectiveness of low-dose, brain-derived neurotrophic 
      and glial-derived neurotrophic factors to counteract the effects of chronic 
      axotomy in promoting axonal regeneration. High-dose brain-derived neurotrophic 
      factor (BDNF) on the other hand, acting through the p75 receptor, inhibits axonal 
      regeneration and may be a factor in stopping regenerating axons from forming 
      neuromuscular connections in skeletal muscle. The immunophilin, FK506, is also 
      effective in promoting axonal regeneration after chronic axotomy. Chronic 
      denervation of SCs (>1 month) severely deters axonal regeneration, although the 
      few motor axons that do regenerate to reinnervate muscles become myelinated and 
      form enlarged motor units in the reinnervated muscles. We found that in vitro 
      incubation of chronically denervated SCs with transforming growth factor-beta 
      re-established their growth-supportive phenotype in vivo, consistent with the 
      idea that the interaction between invading macrophages and denervated SCs during 
      Wallerian degeneration is essential to sustain axonal regeneration by promoting 
      the growth-supportive SC phenotype. Finally, we consider the effectiveness of a 
      brief period of 20 Hz electrical stimulation in promoting the regeneration of 
      axons across the surgical gap after nerve repair.
FAU - Gordon, Tessa
AU  - Gordon T
AD  - Center for Neuroscience, Division of Physical Medicine and Rehabilitation, 
      Faculty of Medicine, University of Alberta, Edmonton, Alberta, Canada. 
      tessa.gordon@ualberta.ca
FAU - Sulaiman, Olawale
AU  - Sulaiman O
FAU - Boyd, J Gordon
AU  - Boyd JG
LA  - eng
PT  - Lecture
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Peripher Nerv Syst
JT  - Journal of the peripheral nervous system : JPNS
JID - 9704532
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Dextrans)
RN  - 0 (Fluoro-Ruby)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Receptor, Nerve Growth Factor)
RN  - 0 (Receptors, Nerve Growth Factor)
RN  - 0 (Rhodamines)
RN  - 0 (Transforming Growth Factor beta)
RN  - 1F7A44V6OU (Colforsin)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Animals
MH  - Autonomic Denervation/methods
MH  - Axons/drug effects/metabolism/radiation effects
MH  - Axotomy/methods
MH  - Brain-Derived Neurotrophic Factor/therapeutic use
MH  - Cell Count
MH  - Colforsin/pharmacology
MH  - Dextrans/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Electric Stimulation
MH  - Evoked Potentials, Motor/physiology
MH  - Humans
MH  - In Vitro Techniques
MH  - Mice
MH  - Mice, Knockout
MH  - Motor Neurons/drug effects/radiation effects
MH  - Muscle Contraction/physiology
MH  - Nerve Degeneration/*prevention & control
MH  - Nerve Growth Factors/*therapeutic use
MH  - Nerve Regeneration/drug effects/radiation effects
MH  - Peripheral Nerve Injuries
MH  - *Peripheral Nerves/drug effects/physiopathology/radiation effects
MH  - Rats
MH  - Receptor, Nerve Growth Factor
MH  - Receptor, trkB/metabolism
MH  - Receptors, Nerve Growth Factor/drug effects/metabolism
MH  - *Recovery of Function/drug effects/radiation effects
MH  - Rhodamines/metabolism
MH  - Schwann Cells/drug effects/metabolism/radiation effects
MH  - Tacrolimus/*therapeutic use
MH  - Time Factors
MH  - Transforming Growth Factor beta/pharmacology
EDAT- 2003/12/04 05:00
MHDA- 2004/02/11 05:00
CRDT- 2003/12/04 05:00
PHST- 2003/12/04 05:00 [pubmed]
PHST- 2004/02/11 05:00 [medline]
PHST- 2003/12/04 05:00 [entrez]
AID - 3029 [pii]
AID - 10.1111/j.1085-9489.2003.03029.x [doi]
PST - ppublish
SO  - J Peripher Nerv Syst. 2003 Dec;8(4):236-50. doi: 
      10.1111/j.1085-9489.2003.03029.x.