PMID- 23353792
OWN - NLM
STAT- MEDLINE
DCOM- 20130618
LR  - 20131121
IS  - 1528-1175 (Electronic)
IS  - 0003-3022 (Linking)
VI  - 118
IP  - 5
DP  - 2013 May
TI  - Neuroprotective effects of dexmedetomidine against glutamate agonist-induced 
      neuronal cell death are related to increased astrocyte brain-derived neurotrophic 
      factor expression.
PG  - 1123-32
LID - 10.1097/ALN.0b013e318286cf36 [doi]
AB  - BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a prominent role in 
      neuroprotection against perinatal brain injury. Dexmedetomidine, a selective 
      agonist of alpha2-adrenergic receptors, also provides neuroprotection against 
      glutamate-induced damage. Because adrenergic receptor agonists can modulate BDNF 
      expression, our goal was to examine whether dexmedetomidine's neuroprotective 
      effects are mediated by BDNF modulation in mouse perinatal brain injury. METHODS: 
      The protective effects against glutamate-induced injury of BDNF and 
      dexmedetomidine alone or in combination with either a neutralizing BDNF antibody 
      or an inhibitor of the extracellular signal-regulated kinase pathway (PD098059) 
      were compared in perinatal ibotenate-induced cortical lesions (n = 10-20 
      pups/groups) and in mouse neuronal cultures (300 muM of ibotenate for 6 h). The 
      effect of dexmedetomidine on BDNF expression was examined in vivo and in vitro 
      with cortical neuronal and astrocyte isolated cultures. RESULTS: Both BDNF and 
      dexmedetomidine produced a significant neuroprotective effect in vivo and in 
      vitro. Dexmedetomidine enhanced Bdnf4 and Bdnf5 transcription and BDNF protein 
      cortical expression in vivo. Dexmedetomidine also enhanced Bdnf4 and Bdnf5 
      transcription and increased BDNF media concentration in isolated astrocyte 
      cultures but not in neuronal cultures. Dexmedetomidine's protective effect was 
      inhibited with BDNF antibody (mean lesion size +/- SD: 577 +/- 148 mum vs. 1028 +/- 213 
      mum, n = 14-20, P < 0.001) and PD098059 in vivo but not in isolated neuron 
      cultures. Finally, PD098059 inhibited the increased release of BDNF induced by 
      dexmedetomidine in astrocyte cultures. CONCLUSION: These results suggest that 
      dexmedetomidine increased astrocyte expression of BDNF through an extracellular 
      signal-regulated kinase-dependent pathway, inducing subsequent neuroprotective 
      effects.
FAU - Degos, Vincent
AU  - Degos V
AD  - Inserm, U676, Paris, France, Universite Paris 7, Paris, France. degosv@gmail.com
FAU - Charpentier, Tifenn Le
AU  - Charpentier TL
FAU - Chhor, Vibol
AU  - Chhor V
FAU - Brissaud, Olivier
AU  - Brissaud O
FAU - Lebon, Sophie
AU  - Lebon S
FAU - Schwendimann, Leslie
AU  - Schwendimann L
FAU - Bednareck, Nathalie
AU  - Bednareck N
FAU - Passemard, Sandrine
AU  - Passemard S
FAU - Mantz, Jean
AU  - Mantz J
FAU - Gressens, Pierre
AU  - Gressens P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anesthesiology
JT  - Anesthesiology
JID - 1300217
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Hypnotics and Sedatives)
RN  - 0 (Neuroprotective Agents)
RN  - 2552-55-8 (Ibotenic Acid)
RN  - 63231-63-0 (RNA)
RN  - 67VB76HONO (Dexmedetomidine)
SB  - IM
MH  - Animals
MH  - Astrocytes/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics
MH  - Cell Death/*drug effects
MH  - Cells, Cultured
MH  - Dexmedetomidine/*pharmacology
MH  - Excitatory Amino Acid Agonists/*toxicity
MH  - Female
MH  - Gene Expression/drug effects
MH  - Hypnotics and Sedatives/*pharmacology
MH  - Ibotenic Acid/toxicity
MH  - MAP Kinase Signaling System/drug effects
MH  - Male
MH  - Mice
MH  - Neurons/*drug effects
MH  - *Neuroprotective Agents
MH  - Phosphorylation
MH  - RNA/biosynthesis/isolation & purification
MH  - Transcription, Genetic/drug effects
EDAT- 2013/01/29 06:00
MHDA- 2013/06/19 06:00
CRDT- 2013/01/29 06:00
PHST- 2013/01/29 06:00 [entrez]
PHST- 2013/01/29 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - 10.1097/ALN.0b013e318286cf36 [doi]
PST - ppublish
SO  - Anesthesiology. 2013 May;118(5):1123-32. doi: 10.1097/ALN.0b013e318286cf36.