PMID- 26526810
OWN - NLM
STAT- MEDLINE
DCOM- 20180212
LR  - 20181203
IS  - 1365-2990 (Electronic)
IS  - 0305-1846 (Linking)
VI  - 42
IP  - 7
DP  - 2016 Dec
TI  - 14,15-epoxyeicosatrienoic acid promotes production of brain derived neurotrophic 
      factor from astrocytes and exerts neuroprotective effects during ischaemic 
      injury.
PG  - 607-620
LID - 10.1111/nan.12291 [doi]
AB  - AIMS: 14,15-Epoxyeicosatrienoic acid (14,15-EET) is abundantly expressed in brain 
      and exerts protective effects against ischaemia. 14,15-EET is hydrolysed by 
      soluble epoxide hydrolase (sEH). sEH(-/-) mice show a higher level of 14,15-EET 
      in the brain. Astrocytes play a pivotal role in neuronal survival under ischaemic 
      conditions. However, it is unclear whether the neuroprotective effect of 
      14,15-EET is associated with astrocytes. METHODS: A mouse model of focal cerebral 
      ischaemia was induced by middle cerebral artery occlusion. Oxygen-glucose 
      deprivation/reoxygenation (OGD/R) was performed on cultured murine astrocytes, 
      neurons and a human cell line. Cell viabilities were measured by 3-(4, 
      5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The 
      mRNA expressions were quantified by real-time PCR. Brain derived neurotrophic 
      factor (BDNF) concentration was measured by ELISA. Protein expressions were 
      quantified by Western blotting. BDNF and peroxisome proliferators-activated 
      receptor gamma (PPAR-gamma) expressions were analysed by confocal microscopy. 
      RESULTS: Decreased infarct volumes, elevated BDNF expression and increased 
      numbers of BDNF/GFAP Glial Fibrillary Acidic Protein double-positive cells were 
      observed in the ischaemic penumbra of sEH(-/-) mice. The decreased infarct 
      volumes of sEH(-/-) mice were diminished by intracerebroventricular injection of 
      a blocker of BDNF receptor. 14,15-EET increases BDNF expression and cell 
      viability of murine astrocytes and U251 cells by BDNF-TrkB Tyrosine receptor 
      kinase-B-extracellular signal-regulated kinase 1/2 signalling during OGD/R. 
      14,15-EET protects neurons from OGD/R by stimulating the production of 
      astrocyte-derived BDNF. 14,15-EET stimulates the production of astrocyte-derived 
      BDNF through PPAR-gamma/p-cAMP-response element binding protein signal pathways. 
      CONCLUSIONS: Our study demonstrates the importance of 14,15-EET-mediated 
      production of astrocyte-derived BDNF for enhancing viability of astrocytes and 
      protecting neurons from the ischaemic injury and provides insights into the 
      mechanism by which 14,15-EET is involved in neuroprotection.
CI  - (c) 2015 British Neuropathological Society.
FAU - Yuan, L
AU  - Yuan L
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University Health Science Center, Beijing, China.
FAU - Liu, J
AU  - Liu J
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University Health Science Center, Beijing, China.
FAU - Dong, R
AU  - Dong R
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University Health Science Center, Beijing, China.
FAU - Zhu, J
AU  - Zhu J
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University Health Science Center, Beijing, China.
FAU - Tao, C
AU  - Tao C
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University Health Science Center, Beijing, China.
FAU - Zheng, R
AU  - Zheng R
AD  - Department of Anatomy, Histology and Embryology, School of Basic Medical 
      Sciences, Peking University Health Science Center, Beijing, China.
FAU - Zhu, S
AU  - Zhu S
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Peking University Health Science Center, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20160106
PL  - England
TA  - Neuropathol Appl Neurobiol
JT  - Neuropathology and applied neurobiology
JID - 7609829
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 81276-03-1 (14,15-epoxy-5,8,11-eicosatrienoic acid)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - FC398RK06S (8,11,14-Eicosatrienoic Acid)
SB  - IM
MH  - 8,11,14-Eicosatrienoic Acid/*analogs & derivatives/metabolism
MH  - Animals
MH  - Astrocytes/drug effects/*metabolism
MH  - Brain Ischemia/*metabolism/*prevention & control
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Epoxide Hydrolases/genetics
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neuroprotective Agents/*metabolism
MH  - Signal Transduction
OTO - NOTNLM
OT  - 14,15-epoxyeicosatrienoic acid
OT  - astrocyte
OT  - brain derived neurotrophic factor
OT  - cerebral ischaemia
OT  - extracellular signal-regulated kinase 1/2
OT  - peroxisome proliferators-activated receptor gamma
EDAT- 2015/11/04 06:00
MHDA- 2018/02/13 06:00
CRDT- 2015/11/04 06:00
PHST- 2015/04/09 00:00 [received]
PHST- 2015/10/09 00:00 [revised]
PHST- 2015/10/27 00:00 [accepted]
PHST- 2015/11/04 06:00 [pubmed]
PHST- 2018/02/13 06:00 [medline]
PHST- 2015/11/04 06:00 [entrez]
AID - 10.1111/nan.12291 [doi]
PST - ppublish
SO  - Neuropathol Appl Neurobiol. 2016 Dec;42(7):607-620. doi: 10.1111/nan.12291. Epub 
      2016 Jan 6.