14,15-epoxyeicosatrienoic acid promotes production of brain derived neurotrophic factor from astrocytes and exerts neuroprotective effects during ischaemic injury.


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-γ) 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-γ/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.


Yuan L,Liu J,Dong R,Zhu J,Tao C,Zheng R,Zhu S




Has Abstract


2016-12-01 00:00:00












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    pub_type: 杂志文章


    authors: Papadopoulos MC,Saadoun S,Woodrow CJ,Davies DC,Costa-Martins P,Moss RF,Krishna S,Bell BA

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    authors: Zotova E,Holmes C,Johnston D,Neal JW,Nicoll JA,Boche D

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    abstract::A demyelinating perivascular condition has been observed in the optic nerves of three cats, the lesions of which included the following features: thinly myelinated and demyelinated axons, few normal oligodendrocytes, astroglial scar tissue, lymphocytes, plasma cells, mononuclear phagocytic cells and lipid-laden cells....

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    authors: Cook RD

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    pub_type: 历史文章,杂志文章


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    pub_type: 杂志文章,评审


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    pub_type: 杂志文章


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    pub_type: 杂志文章


    authors: Garcia-Esparcia P,Hernández-Ortega K,Ansoleaga B,Carmona M,Ferrer I

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    pub_type: 杂志文章


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  • Monocytes of patients with amyotrophic lateral sclerosis linked to gene mutations display altered TDP-43 subcellular distribution.

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    journal_title:Neuropathology and applied neurobiology

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    更新日期:1986-11-01 00:00:00

  • The cellular origin of lysosomal enzymes in the plaque in multiple sclerosis. II. A histochemical study with combined demonstration of myelin and acid phosphatase.

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    journal_title:Neuropathology and applied neurobiology

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    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章


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  • Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage.

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    pub_type: 杂志文章


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  • The human chromosome 22-located genes and malignancies of the central nervous system.

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    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章,评审


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    更新日期:1996-10-01 00:00:00

  • Telomeric alterations in the default mode network during the progression of Alzheimer's disease: Selective vulnerability of the precuneus.

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    pub_type: 杂志文章


    authors: Mahady LJ,He B,Malek-Ahmadi M,Mufson EJ

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    pub_type: 杂志文章


    authors: Paradisi M,Fernández M,Del Vecchio G,Lizzo G,Marucci G,Giulioni M,Pozzati E,Antonelli T,Lanzoni G,Bagnara GP,Giardino L,Calzà L

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    authors: Marsan E,Baulac S

    更新日期:2018-02-01 00:00:00

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    pub_type: 杂志文章


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  • Review: the long-term consequences of microglial activation following acute traumatic brain injury.

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    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章,评审


    authors: Smith C

    更新日期:2013-02-01 00:00:00

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    journal_title:Neuropathology and applied neurobiology

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    journal_title:Neuropathology and applied neurobiology

    pub_type: 杂志文章


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    更新日期:2021-02-01 00:00:00