Brain Free Fatty Acids, Edema, and Mortality in Gerbils Subjected to Transient, Bilateral Ischemia, and Effect of Barbiturate Anesthesia

Yoshida, Shigeaki; Inoh, Satoshi; Asano, Takao; Sano, Keiji; Shimasaki, Hiroyuki; Ueta, Nobuo

doi:10.1111/j.1471-4159.1983.tb13567.x

Cited by 109 publications

(42 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the major FFAs, arachidonic and stearic acids arise primarily from membrane lipids, which is consistent with the reduction in the brain phospholipids during hypoxia (25) and ischemia (26). Membrane phos pholipids are strongly implicated in synaptic transmission (27,28) and phospholipid metabolism dysfunction could impair synaptic transmission (29,30). In addition, it has been reported that fatty acids inhibit oxidative phosphorylation of in vitro mito chondrial preparations (31 ), and arachidonic acid has been shown to be capable of inducing brain edema in vitro (32) and in vivo (33).…”

Section: Discussionmentioning

confidence: 55%

Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia.

1984

View full text Add to dashboard Cite

Abstract-The concentrations of acetylcholine (Ach) and choline in various brain regions of rats with and without cerebral ischemia and the effects of 6-(10-hydroxy decyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone, CV-2619) on the levels of these parameters were investigated.Cerebral ischemia was induced by a 200-sec occlusion of both common carotid arteries in animals in which both vertebral arteries had been permanently cauterized.The concentrations of Ach and choline in the brain were determined by means of pyrolysis gas chromato graphy.In normal rats, CV-2619 (10, 30 and 100 mg/kg, i.p.) did not alter the concentrations of Ach and choline in the brain regions examined. In the ischemic rats, a significant decrease in Ach and a marked increase in choline were observed in the cerebral cortex, hippocampus, striatum, and diencephalon. A slight increase in the concentration of choline was also observed in the cerebellum and brain stem. Pretreatment with CV-261 9 (10 mg/kg, i.p.) inhibited the decrease in Ach and the increase in choline in the forebrain regions.Moreover, the same dose of CV-261 9 inhibited the increment of lactate content and tended to inhibit the decrement of ATP content in the cerebral cortex. These results indicate that CV-261 9 inhibits alterations of the concentrations of Ach and choline in the brain of the ischemic rats; this inhibition may be due to the ameliorating effect of CV-261 9 on the dis turbance of cerebral energy metabolism under ischemic conditions.

show abstract

Section: Discussionmentioning

confidence: 55%

Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia.

1984

View full text Add to dashboard Cite

show abstract

“…Indeed, added AA induces the mitochondrial PT, which in turns causes cytochrome c release, and blocking the PT-inducing effects of AA with CsA also blocks commitment to apoptosis. Further work will be needed to assess whether this paradigm also applies to other cell types, but the identification of mitochondria as early targets of AA may have far-reaching implications for conditions like brain ischemia where the increase of AA is a key pathogenetic event, and prominent mitochondrial swelling in situ can be observed (53)(54)(55). Remarkably, neurons were protected from ischemia-reperfusion damage through inhibition of the PTP by CsA (55,56), which also completely prevented mitochondrial swelling in situ (55).…”

Section: Discussionmentioning

confidence: 99%

Arachidonic Acid Causes Cell Death through the Mitochondrial Permeability Transition

Scorrano¹,

Penzo²,

Petronilli³

et al. 2001

Journal of Biological Chemistry

281

199

View full text Add to dashboard Cite

We have investigated the effects of arachidonic and palmitic acids in isolated rat liver mitochondria and in rat hepatoma MH1C1 cells. We show that both compounds induce the mitochondrial permeability transition (PT). At variance from palmitic acid, however, arachidonic acid causes a PT at concentrations that do not cause PT-independent depolarization or respiratory inhibition, suggesting a specific effect on the PT pore. When added to intact MH1C1 cells, arachidonic acid but not palmitic acid caused a mitochondrial PT in situ that was accompanied by cytochrome c release and rapidly followed by cell death. All these effects of arachidonic acid could be prevented by cyclosporin A but not by the phospholipase A 2 inhibitor aristolochic acid. In contrast, tumor necrosis factor ␣ caused phospholipid hydrolysis, induction of the PT, cytochrome c release, and cell death that could be inhibited by both cyclosporin A and aristolochic acid. These findings suggest that arachidonic acid produced by cytosolic phospholipase A 2 may be a mediator of tumor necrosis factor ␣ cytotoxicity in situ through induction of the mitochondrial PT.The mitochondrial PT 1 is a regulated permeability increase to solutes with molecular masses up to 1,500 Da mediated by opening of a high conductance channel, the PTP, whose molecular nature remains debated (1). The PT is modulated by a variety of effectors of cell death, including reactive oxygen species that are produced early by mitochondria after stimulation of the TNF␣ receptor (2). Early evidence indicated that PTP opening can mediate cell death caused by oxidative stress and anoxia through ATP depletion and dysregulation of Ca 2ϩ homeostasis (3-5). The PT could also be instrumental in the release of intermembrane proteins such as cytochrome c (6, 7), which plays a key role in caspase 9 activation (8), and apoptosis-inducing factor (9), which causes nuclear degradation independent of caspase activation (10).Mitochondria play a role in apoptotic signaling in the TNF␣ pathway, which is activated by ligand binding to the TNF␣ receptor. Several cytosolic proteins are recruited to the receptor death domain, which in turn leads to the production of a variety of second messengers. As a result, multiple protein-mediated signaling cascades are activated, including caspase-dependent and caspase-independent pathways, phospholipases, protein kinases, and protein phosphatases (see Ref. 11 for a critical and comprehensive review). Lipid mediators may be involved both in signaling and in the late cellular responses by receptors of the TNF␣ superfamily, and solid evidence indicates that mitochondria can be the target of lipid mediators of pathophysiological relevance. Ceramide produced by acidic sphingomyelinase is essential for production of GD3 ganglioside, a cell death inducer (12) that is able to cause PT-dependent apoptosis (13) with cytochrome c release and caspase activation (14). Ceramide itself has prominent effects on mitochondria (14 -19) and may turn physiological Ca 2ϩ signals acting through ...

show abstract

“…Based upon our data, however, it is not possible at the present time to pinpoint their origins. The decreases seen in spinal cord FFA and acyl2Gro following the termination of compression may also be due to several mechanisms (42), including equilibration with the FFA in blood and cerebrospinal fluid, oxidation of the fatty acids as an energy source, reacylation into glycerophospholipids, and enzymic and nonenzymatic peroxidation of the polyunsaturated fatty acids (43)(44)(45)(46)(47).…”

Section: Discussionmentioning

confidence: 99%

Membrane lipid changes in laminectomized and traumatized cat spinal cord.

Demediuk¹,

Saunders²,

Anderson³

et al. 1985

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

157

105

View full text Add to dashboard Cite

Free fatty acid (FFA), diacyiglycerol (acyl2-Gro), icosanoid, phospholipid, and cholesterol levels were measured in samples of cat spinal cord (L2) that were frozen in situ (i) with vertebrae intact, (ii) at various times after laminectomy, and (iu) at various times after laminectomy with compression trauma to the spinal cord. Tissue samples either were grossly dissected into gray and white portions prior to FFA and acyl2Gro analysis or were used whole for the other lipid types. Gray matter total FFA and acyl2Gro values were abnormally high in samples frozen with vertebrae intact and in those frozen 10 min after laminectomy. This indicates that the surgical procedures resulted in some perturbation of spinal cord lipid metabolism. If the experimental animals were allowed to recover for 90 min after laminectomy, the gray matter FFA and acyl2Gro levels were greatly reduced. Compression of the spinal cord with a 170-g weight for 1, 3, or 5mm (following 90 min of recovery after laminectomy) caused significant elevations of total FFA, acyl2Gro, icosanoids, and phosphatidic acid and significant decreases in ethalamine plasmalogens and cholesterol. Among the total FFA, arachidonic acid was found to have the largest relative increase. Comparisons of gray and white matter demonstrate that, in general, changes in white matter FFA and acyl2Gro were similar to those seen in gray matter. However, the increases in white matter levels of FFA and acyl2Gro were delayed, occurring after the elevations in gray matter. For some FFA (e.g., arachidonate), the rise in white matter occurred as gray matter levels were decreasing. This suggests that the initial alteration in spinal cord lipid metabolism after trauma was in gray matter but, with time, spread radially into white matter.

show abstract

Brain Free Fatty Acids, Edema, and Mortality in Gerbils Subjected to Transient, Bilateral Ischemia, and Effect of Barbiturate Anesthesia

Cited by 109 publications

References 51 publications

Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia.

Effects of idebenone (CV-2619) on the concentrations of acetylcholine and choline in various brain regions of rats with cerebral ischemia.

Arachidonic Acid Causes Cell Death through the Mitochondrial Permeability Transition

Membrane lipid changes in laminectomized and traumatized cat spinal cord.

Contact Info

Product

Resources

About