PMID- 23735240
OWN - NLM
STAT- MEDLINE
DCOM- 20131105
LR  - 20220311
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 10
DP  - 2013 Jun 4
TI  - Beneficial effect of TNF-alpha inhibition on diabetic peripheral neuropathy.
PG  - 69
LID - 10.1186/1742-2094-10-69 [doi]
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is an important inflammatory factor 
      produced by activated macrophages and monocytes and plays an important role in 
      the pathogenesis of diabetic peripheral neuropathy (DPN). To evaluate the effect 
      of TNF-alpha signaling suppression and the potential of TNF-alpha in the treatment of 
      DPN, a recombinant human TNF-alpha receptor-antibody fusion protein (rhTNFR:Fc) was 
      used. We focused on the pathophysiology of the sciatic nerve and examined the 
      expression of myelin basic protein (MBP) under DPN status with or without TNF-alpha 
      inhibition. METHODS: The DPN rat model was generated by intraperitoneal injection 
      of streptozotocin and by feeding with a high-fat, high-sugar diet. The nerve 
      conduction velocity (NCV) in sciatic nerve of rat was monitored over a period of 
      four weeks. The histopathological changes in nerve tissue were examined through 
      traditional tissue histology and ultrastructure transmission electron microscopy 
      (TEM). The expression of MBP was examined through western blot analysis. RESULTS: 
      The DPN induced rats showed significant signs of nerve damage including lower 
      NCV, demyelination of nerve fibers, disorganization of lamellar and axonal 
      structures, and decreased expression of MBP in the nerve tissue. The inhibition 
      of TNF-alpha in the DPN rats resulted in a significant recovery from those symptoms 
      compared to the DPN rats. CONCLUSIONS: Our study demonstrates that TNF-alpha plays a 
      key role in the pathogenesis of DPN and its inhibition by rhTNFR:Fc can prove to 
      be a useful therapeutic strategy for the treatment of and/or prevention from DPN 
      symptoms.
FAU - Shi, Xiaohong
AU  - Shi X
AD  - Department of Endocrinology, Jinshan Hospital, Fudan University, 1508 Longhang 
      Road, Shanghai 201508, PR China.
FAU - Chen, Yinghui
AU  - Chen Y
FAU - Nadeem, Lubna
AU  - Nadeem L
FAU - Xu, Guoxiong
AU  - Xu G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130604
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Axons/pathology
MH  - Blotting, Western
MH  - Diabetes Mellitus, Experimental/complications/drug therapy/pathology
MH  - Diabetic Neuropathies/*drug therapy
MH  - Humans
MH  - Immunohistochemistry
MH  - Male
MH  - Microscopy, Electron, Transmission
MH  - Motor Neurons/drug effects
MH  - Myelin Basic Protein/biosynthesis
MH  - Nerve Fibers/pathology
MH  - Neural Conduction/physiology
MH  - Peripheral Nervous System Diseases/*drug therapy
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Tumor Necrosis Factor, Type I/therapeutic use
MH  - Recombinant Fusion Proteins/therapeutic use
MH  - Sciatic Nerve/pathology/ultrastructure
MH  - Sensory Receptor Cells/drug effects
MH  - Tumor Necrosis Factor-alpha/*antagonists & inhibitors
PMC - PMC3679954
EDAT- 2013/06/06 06:00
MHDA- 2013/11/06 06:00
PMCR- 2013/06/04
CRDT- 2013/06/06 06:00
PHST- 2013/04/16 00:00 [received]
PHST- 2013/05/20 00:00 [accepted]
PHST- 2013/06/06 06:00 [entrez]
PHST- 2013/06/06 06:00 [pubmed]
PHST- 2013/11/06 06:00 [medline]
PHST- 2013/06/04 00:00 [pmc-release]
AID - 1742-2094-10-69 [pii]
AID - 10.1186/1742-2094-10-69 [doi]
PST - epublish
SO  - J Neuroinflammation. 2013 Jun 4;10:69. doi: 10.1186/1742-2094-10-69.