Rapid production of diacylglycerols enriched in arachidonate and stearate during early brain ischemia

Aveldaño, Marta I.; Bazán, Nicolás G.

doi:10.1111/j.1471-4159.1975.tb04432.x

Cited by 177 publications

(57 citation statements)

References 15 publications

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“…Sugiura et al (2001) have earlier reported that there is a very early postmortal increase in 2-AG levels in the rat brain that occurs within the first 30 seconds after decapitation, and that can be prevented by immediately freezing the brain in liquid nitrogen. A possible mechanism offered to account for that change is that decapitation leads to rapid breakdown of inositol phospholipids and the subsequent generation of diacylglycerol (Aveldano and Bazan, 1975) that can be further metabolized by diacylglycerol lipase to 2-AG. Although possible, it is unlikely that such a rapid early increase in 2-AG occurred in the neurosurgically removed samples, because removal of the samples is much faster than in animals following decapitation and the conditions are also different.…”

Section: Postmortal Depletion Of Brain 2-ag Levelsmentioning

confidence: 99%

Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain

Palkovits¹,

Harvey-White²,

Liu³

et al. 2008

Neuroscience

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Tissue levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) have been determined in 16 regions and nuclei from human brains, using liquid chromatography/inline mass spectrometry. Measurements in brain samples stored at −80°C for 2 months to 13 years indicated that endocannabinoids were stable under such conditions. In contrast, the postmortal delay had a strong effect on brain endocannabinoid levels, as documented in brain samples microdissected and frozen 1 to 6h postmortem, and in neurosurgical samples 0, 5, 30, 60, 180 and 360 min after their removal from the brain. The tissue levels of AEA increased continuously and in a region-dependent manner from one hour after death, increasing about 7-fold by 6h postmortem. In contrast, concentrations of 2-AG, which were 10 to 100-times higher in human brain regions than those of AEA, rapidly declined: within the first hour, 2-AG levels dropped to 25-35% of the initial ('0 min') value, where after they remained relatively stable. As analyzed in samples removed 1-1.5h post mortem, AEA levels ranged from a high of 96.3 fmol/mg tissue in the nucleus accumbens to a low of 25.0 fmol/ mg in the cerebellum. 2-AG levels varied 8-fold, from 8.6 pmol/mg in the lateral hypothalamus to 1.1 pmol/mg in the nucleus accumbens. Relative levels of AEA and 2-AG varied from region to region, with the 2-AG:AEA ratio being high in the sensory spinal trigeminal nucleus (140:1), the spinal dorsal horn (136:1) and the lateral hypothalamus (98:1) and low in the nucleus accumbens (16:1) and the striatum (31:1). The results highlight the pitfall of analyzing endocannabinoid content in brain samples of variable postmortal delay, and document differential distribution of the two main endocannabinoids in the human brain.

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Section: Postmortal Depletion Of Brain 2-ag Levelsmentioning

confidence: 99%

Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain

Palkovits¹,

Harvey-White²,

Liu³

et al. 2008

Neuroscience

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“…Because ECS and ischemia activate the PLCmediated release of 20:4-DAG (8,33,34), we investigated whether deficiency of DGK , which terminates 20:4-DAG signals, would affect the seizure response to ECS. We found that male and female DGK -deficient mice were more resistant to ECS, displaying shorter tonic seizures and faster recovery than DGK ϩ/ϩ mice.…”

Section: Down-regulation Of 20:4 -Inositol Lipid Signaling and Resistmentioning

confidence: 99%

Diacylglycerol kinase ɛ regulates seizure susceptibility and long-term potentiation through arachidonoyl– inositol lipid signaling

Turco

Tang

Topham

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

152

167

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Arachidonoyldiacylglycerol (20:4-DAG) is a second messenger derived from phosphatidylinositol 4,5-bisphosphate and generated by stimulation of glutamate metabotropic receptors linked to G proteins and activation of phospholipase C. 20:4-DAG signaling is terminated by its phosphorylation to phosphatidic acid, catalyzed by diacylglycerol kinase (DGK). We have cloned the murine DGK gene that showed, when expressed in COS-7 cells, selectivity for 20:4-DAG. The significance of DGK in synaptic function was investigated in mice with targeted disruption of the DGK . DGK ؊/؊ mice showed a higher resistance to eletroconvulsive shock with shorter tonic seizures and faster recovery than DGK ؉/؉ mice. The phosphatidylinositol 4,5-bisphosphate-signaling pathway in cerebral cortex was greatly affected, leading to lower accumulation of 20:4-DAG and free 20:4. Also, long-term potentiation was attenuated in perforant path-dentate granular cell synapses. We propose that DGK contributes to modulate neuronal signaling pathways linked to synaptic activity, neuronal plasticity, and epileptogenesis.

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“…28 Reperfusion enhances the metabolism of free fatty acids along the arachidonic acid cascade, which has been the focus of much of the research in the area of stroke. A significant source of arachidonate is alkylacylglycero-3-phosphorylcholine, which is also the precursor of PAF.…”

Section: Discussionmentioning

confidence: 99%

Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits.

Lindsberg

Yue

Frerichs

et al. 1990

Stroke

100

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Platelet-activating factor is a potent mediator of inflammation, which has untoward effects on cerebrovascular and neural elements. While several investigators have reported attenuation of ischemic damage after treatment with antagonists of platelet-activating factor, no study has proved endogenous production of platelet-activating factor in ischemia of the central nervous system. We hypothesized that endogenous production of platelet-activating factor participates in the early pathologic manifestations of deteriorating stroke. In 12 rabbits, we found tissue levels of platelet-activating factor measured by the release of serotonin from washed

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Rapid production of diacylglycerols enriched in arachidonate and stearate during early brain ischemia

Cited by 177 publications

References 15 publications

Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain

Regional distribution and effects of postmortal delay on endocannabinoid content of the human brain

Diacylglycerol kinase ɛ regulates seizure susceptibility and long-term potentiation through arachidonoyl– inositol lipid signaling

Evidence for platelet-activating factor as a novel mediator in experimental stroke in rabbits.

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