Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain

Yoshida, Shigeaki; Inoh, Satoshi; Asano, Takao; Sano, Keiji; Kubota, Masaru; Shimazaki, Hiroyuki; Ueta, Nobuo

doi:10.3171/jns.1980.53.3.0323

Cited by 330 publications

(126 citation statements)

References 41 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…14 (upper part) shows, this was not the ca se. These results also showed that increases in total FF A co ntent (upper panel) and in polyenoic fatty acids (lower panel) persisted for some time in the re circulation period (see also Yoshida et al ., 1980). We will return to this finding in a later paragraph.…”

Section: Effe Cts Of a Trickling Oxygen Supplysupporting

confidence: 53%

“…13). Somewhat different results were reported by Yoshida et al (1980), who fo und that 30 min of ischemia, induced in gerbils by bilateral carotid artery ligation, signifi cantly reduced the tissue co ntent of PE, but not of Pc. However, these authors measured neither indi vidual fatty acids nor the fatty acid co mposition of PE .…”

Section: Effe Cts Of a Trickling Oxygen Supplymentioning

confidence: 59%

See 1 more Smart Citation

Cell Damage in the Brain: A Speculative Synthesis

Siesjö

1981

J Cereb Blood Flow Metab

1,723

135

View full text Add to dashboard Cite

Section: Effe Cts Of a Trickling Oxygen Supplysupporting

confidence: 53%

Section: Effe Cts Of a Trickling Oxygen Supplymentioning

confidence: 59%

Cell Damage in the Brain: A Speculative Synthesis

Siesjö

1981

J Cereb Blood Flow Metab

1,723

135

View full text Add to dashboard Cite

“…amounts, but accumulates under adverse conditions such as cerebral ischemia (Bazan, 1970;Yoshida et al, 1980;Gardiner et al, 1981;Kinouchi et al, 1990). Release of the free fatty acid is attributable to breakdown of membrane phospholipids by activa tion of phospholipases (U memura et al, 1992).…”

mentioning

confidence: 99%

Swelling, Acidosis, and Irreversible Damage of Glial Cells from Exposure to Arachidonic Acid in vitro

Staub¹,

Winkler²,

Peters³

et al. 1994

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Swelling and damage of C6 glioma cells and of primary cultured astrocytes were analyzed in vitro during incubation with arachidonic acid (AA; 20:4). The cells were suspended in a physiological medium supplemented with AA at concentrations of 0.001–1.0 m M. Cell swelling was quantified by flow cytometry with hydrodynamic focusing. Flow cytometry was also utilized for assessment of cell viability by exclusion of the fluorescent dye propidium iodide and for measurement of the intracellular pH (pHi) by 2′,7′-bis-(2-carboxyethyl)−5(and −6)carboxyfluorescein. Administration of AA caused an immediate dose-dependent swelling of C6 glioma cells, even at a concentration of 0.01 m M. At this level cell volume increased within 20 min to 105.0% of control, at 0.1 m M to 111.0%, while at 1.0 m M to 123.7%. Following a phase of rapid cell volume increase, swelling leveled off during the subsequent observation period of 70 min. Viability of the C6 glioma cells was 90% under control conditions. It remained unchanged after raising AA concentrations to 0.1 m M. At 0.5 m M, however, cell viability fell to 72.8%, and at 1.0 m M to 32.7%. pHi of the glioma cells was 7.3 under control conditions. In parallel with the early swelling phase, AA led to a dose-dependent decrease of the intracellular pH and an elevated lactate production of the cells. During incubation with 0.1 m M AA, pHi decreased to 7.06 after 5 min, but recovered to normal subsequently. In addition, swelling-inducing properties of linoleic (18:2) or stearic (18:0) acid were analyzed for evaluation of the specificity of glial swelling induced by AA. Whereas stearic acid (0.1 m M) failed to induce a swelling response, linoleic acid (0.1 m M) was found to be effective. The volume increase of the glial cells, however, was only half of that found during exposure to AA at the same concentration. Further, glial swelling from AA or linoleic acid was completely inhibited by the aminosteroid U-74389F, an antagonist of lipid peroxidation. Finally, omission of Na+ ions in the suspension medium with replacement by choline led also to inhibition of the cell volume increase by AA. Experiments using astrocytes from primary culture confirmed the swelling-inducing properties of AA at a quantitative level, whereas vulnerability of the cells to AA was increased. The present results demonstrate an important role of AA in cytotoxic swelling and irreversible damage of glial cells at concentrations that occur in vivo in cerebral ischemia or trauma. The damaging potential of AA might be enhanced by a concurrently evolving intracellular acidosis, stimulating the formation of oxygen-derived free radicals and lipid peroxidation.

show abstract

“…3 Acute ischemic stroke is known to be associated with glutathione depletion and metabolism of membrane-bound arachidonic acid. [4][5][6] Under these conditions, 12-lipoxygenase has been recognized as a key pathway of arachidonic acid metabolism, which has been directly implicated in middle-cerebral artery occlusion (MCAO)-induced injury of the brain. 7,8 In this work, we report the loss of miR-29b at the infarct site after stroke by a 12-lipoxygenase-dependent mechanism.…”

Section: Introductionmentioning

confidence: 99%

Loss of miR-29b following Acute Ischemic Stroke Contributes to Neural Cell Death and Infarct Size

Khanna

Rink

Ghoorkhanian

et al. 2013

J Cereb Blood Flow Metab

102

109

View full text Add to dashboard Cite

Glutathione depletion and 12-lipoxygenase-dependent metabolism of arachidonic acid are known to be implicated in neurodegeneration associated with acute ischemic stroke. The objective of this study was to investigate the significance of miR-29 in neurodegeneration associated with acute ischemic stroke. Neural cell death caused by arachidonic acid insult of glutathionedeficient cells was preceded by a 12-lipoxygenase-dependent loss of miR-29b. Delivery of miR-29b mimic to blunt such loss was neuroprotective. miR-29b inhibition potentiated such neural cell death. 12-Lipoxygenase knockdown and inhibitors attenuated the loss of miR-29b in challenged cells. In vivo, stroke caused by middle-cerebral artery occlusion was followed by higher 12-lipoxygenase activity and loss of miR-29b as detected in laser-captured infarct site tissue. 12-Lipoxygenase knockout mice demonstrated protection against such miR loss. miR-29b gene delivery markedly attenuated stroke-induced brain lesion. Oral supplementation of a-tocotrienol, a vitamin E 12-lipoxygenase inhibitor, rescued stroke-induced loss of miR-29b and minimized lesion size. This work provides the first evidence demonstrating that loss of miR-29b at the infarct site is a key contributor to stroke lesion. Such loss is contributed by activity of the 12-lipoxygenase pathway providing maiden evidence linking arachidonic acid metabolism to miR-dependent mechanisms in stroke.

show abstract

Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain

Cited by 330 publications

References 41 publications

Cell Damage in the Brain: A Speculative Synthesis

Cell Damage in the Brain: A Speculative Synthesis

Swelling, Acidosis, and Irreversible Damage of Glial Cells from Exposure to Arachidonic Acid in vitro

Loss of miR-29b following Acute Ischemic Stroke Contributes to Neural Cell Death and Infarct Size

Contact Info

Product

Resources

About