PMID- 23496862
OWN - NLM
STAT- MEDLINE
DCOM- 20130813
LR  - 20220330
IS  - 1471-2202 (Electronic)
IS  - 1471-2202 (Linking)
VI  - 14
DP  - 2013 Mar 15
TI  - Etanercept attenuates traumatic brain injury in rats by reducing early microglial 
      expression of tumor necrosis factor-alpha.
PG  - 33
LID - 10.1186/1471-2202-14-33 [doi]
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is elevated early in injured 
      brain after traumatic brain injury (TBI), in humans and in animals. Etanercept (a 
      TNF-alpha antagonist with anti-inflammatory effects) attenuates TBI in rats by 
      reducing both microglial and astrocytic activation and increased serum levels of 
      TNF-alpha. However, it is not known whether etanercept improves outcomes of TBI by 
      attenuating microglia-associated, astrocytes-associated, and/or 
      neurons-associated TNF-alpha expression in ischemic brain. A well clinically relevant 
      rat model, where a lateral fluid percussion is combined with systemic 
      administration of etanercept immediately after TBI, was used. The neurological 
      severity score and motor function was measured on all rats preinjury and on day 3 
      after etanercept administration. At the same time, the neuronal and glial 
      production of TNF-alpha was measured by Immunofluorescence staining. In addition, 
      TNFalpha contents of ischemic cerebral homogenates was measured using commercial 
      enzyme-linked immunosorbent assay kits. RESULTS: In addition to inducing brain 
      ischemia as well as neurological and motor deficits, TBI caused significantly 
      higher numbers of microglia-TNF-alpha double positive cells, but not neurons-TNF-alpha or 
      astrocytes-TNF-alpha double positive cells in the injured brain areas than did the 
      sham operated controls, when evaluated 3 days after TBI. The TBI-induced cerebral 
      ischemia, neurological motor deficits, and increased numbers of microglia-TNF-alpha 
      double positive cells and increased TNF-alpha levels in the injured brain were all 
      significantly attenuated by etanercept therapy. CONCLUSION: This finding 
      indicates that early microglia overproduction of TNF-alpha in the injured brain 
      region after TBI contributes to cerebral ischemia and neurological motor 
      deficits, which can be attenuated by etanercept therapy. Studies in this model 
      could provide insight into the mechanisms underlying neurological motor 
      disturbance in brain-injured patients.
FAU - Chio, Chung-Ching
AU  - Chio CC
AD  - Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan.
FAU - Chang, Chin-Hong
AU  - Chang CH
FAU - Wang, Che-Chuan
AU  - Wang CC
FAU - Cheong, Chong-Un
AU  - Cheong CU
FAU - Chao, Chien-Ming
AU  - Chao CM
FAU - Cheng, Bor-Chih
AU  - Cheng BC
FAU - Yang, Chung-Zhing
AU  - Yang CZ
FAU - Chang, Ching-Ping
AU  - Chang CP
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20130315
PL  - England
TA  - BMC Neurosci
JT  - BMC neuroscience
JID - 100966986
RN  - 0 (Aif1 protein, rat)
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Calcium-Binding Proteins)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Microfilament Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 7OL20RET2I (triphenyltetrazolium)
RN  - OP401G7OJC (Etanercept)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology/*therapeutic use
MH  - Brain Injuries/complications/*drug therapy
MH  - Calcium-Binding Proteins/metabolism
MH  - Disease Models, Animal
MH  - Etanercept
MH  - Gene Expression Regulation/drug effects
MH  - Immunoglobulin G/pharmacology/*therapeutic use
MH  - Male
MH  - Microfilament Proteins/metabolism
MH  - Microglia/*drug effects/*metabolism
MH  - Nerve Tissue Proteins/metabolism
MH  - Nervous System Diseases/etiology/prevention & control
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Tumor Necrosis Factor/*therapeutic use
MH  - Tetrazolium Salts
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC3636122
EDAT- 2013/03/19 06:00
MHDA- 2013/08/14 06:00
PMCR- 2013/03/15
CRDT- 2013/03/19 06:00
PHST- 2012/11/08 00:00 [received]
PHST- 2013/03/07 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2013/08/14 06:00 [medline]
PHST- 2013/03/15 00:00 [pmc-release]
AID - 1471-2202-14-33 [pii]
AID - 10.1186/1471-2202-14-33 [doi]
PST - epublish
SO  - BMC Neurosci. 2013 Mar 15;14:33. doi: 10.1186/1471-2202-14-33.