PMID- 17825990
OWN - NLM
STAT- MEDLINE
DCOM- 20071214
LR  - 20211103
IS  - 0304-3940 (Print)
IS  - 0304-3940 (Linking)
VI  - 425
IP  - 3
DP  - 2007 Oct 2
TI  - Inhibitory effect on cerebral inflammatory agents that accompany traumatic brain 
      injury in a rat model: a potential neuroprotective mechanism of recombinant human 
      erythropoietin (rhEPO).
PG  - 177-82
AB  - Erythropoietin (EPO) has recently been shown to have a neuroprotective effect in 
      animal models of traumatic brain injury (TBI). However, the precise mechanisms 
      remain unclear. Cerebral inflammation plays an important role in the pathogenesis 
      of secondary brain injury after TBI. We, therefore, tried to analyze how 
      recombinant human erythropoietin (rhEPO) might effect the inflammation-related 
      factors common to TBI: nuclear factor kappa B (NF-kappaB), interleukin-1beta 
      (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and 
      intercellular adhesion molecule-1 (ICAM-1) in a rat TBI model. Male rats were 
      given 0 or 5000 units/kg injections of rhEPO 1h post-injury and on days 1, 2 and 
      3 after surgery. Brain samples were extracted at 3 days after trauma. We measured 
      NF-kappaB by electrophoretic mobility shift assay (EMSA); IL-1beta, TNF-alpha and 
      IL-6 by enzyme-linked immunosorbent assay (ELISA); ICAM-1 by 
      immunohistochemistry; brain edema by wet/dry method; blood-brain barrier (BBB) 
      permeability by Evans blue extravasation and cortical apoptosis by terminal 
      deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method. We 
      found that NF-kappaB, pro-inflammatory cytokines and ICAM-1 were increased in all 
      injured animals. In animals given rhEPO post-TBI, NF-kappaB, IL-1beta, TNF-alpha 
      and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of 
      IL-6 showed no change after rhEPO treatment. Administration of rhEPO reduced 
      brain edema, BBB permeability and apoptotic cells in the injured brain. In 
      conclusion, post-TBI rhEPO administration may attenuate inflammatory response in 
      the injured rat brain, and this may be one mechanism by which rhEPO improves 
      outcome following TBI.
FAU - Chen, Gang
AU  - Chen G
AD  - Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing 
      University, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China. 
      nju_neurosurgery@163.com
FAU - Shi, Ji Xin
AU  - Shi JX
FAU - Hang, Chun Hua
AU  - Hang CH
FAU - Xie, Weiying
AU  - Xie W
FAU - Liu, Jian
AU  - Liu J
FAU - Liu, Xiaoming
AU  - Liu X
LA  - eng
PT  - Journal Article
DEP - 20070819
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 11096-26-7 (Erythropoietin)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology/therapeutic use
MH  - Apoptosis/drug effects/physiology
MH  - Blood-Brain Barrier/drug effects/metabolism
MH  - Brain Edema/drug therapy/etiology/physiopathology
MH  - Brain Injuries/complications/*drug therapy/physiopathology
MH  - Cerebral Cortex/*drug effects/metabolism/physiopathology
MH  - Cytoprotection/drug effects/physiology
MH  - Disease Models, Animal
MH  - Encephalitis/*drug therapy/etiology/physiopathology
MH  - Erythropoietin/*pharmacology/therapeutic use
MH  - Humans
MH  - Inflammation Mediators/*antagonists & inhibitors/metabolism
MH  - Intercellular Adhesion Molecule-1/drug effects/metabolism
MH  - Interleukin-1beta/antagonists & inhibitors/metabolism
MH  - Interleukin-6/antagonists & inhibitors/metabolism
MH  - Male
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Neuroprotective Agents/pharmacology/therapeutic use
MH  - Rats
MH  - Rats, Wistar
MH  - Recombinant Proteins/pharmacology/therapeutic use
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/metabolism
EDAT- 2007/09/11 09:00
MHDA- 2007/12/15 09:00
CRDT- 2007/09/11 09:00
PHST- 2007/06/05 00:00 [received]
PHST- 2007/07/27 00:00 [revised]
PHST- 2007/08/11 00:00 [accepted]
PHST- 2007/09/11 09:00 [pubmed]
PHST- 2007/12/15 09:00 [medline]
PHST- 2007/09/11 09:00 [entrez]
AID - S0304-3940(07)00884-1 [pii]
AID - 10.1016/j.neulet.2007.08.022 [doi]
PST - ppublish
SO  - Neurosci Lett. 2007 Oct 2;425(3):177-82. doi: 10.1016/j.neulet.2007.08.022. Epub 
      2007 Aug 19.