Mechanism of Arachidonic Acid Liberation During Ischemia in Gerbil Cerebral Cortex

Abe, Kōji; Kogure, Kyuya; Yamamoto, Hirotaka; Imazawa, Masaoki; Miyamoto, Kenji

doi:10.1111/j.1471-4159.1987.tb04121.x

Cited by 267 publications

(112 citation statements)

References 42 publications

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“…, 1984). Hydrolysis of phosphoinositides into di acylglycerol and inositol phosphate after ischemia (Abe et al, 1987) may also enhance PKC activity.…”

Section: Discussionmentioning

confidence: 99%

Staurosporine, a Novel Protein Kinase C Inhibitor, Prevents Postischemic Neuronal Damage in the Gerbil and Rat

Hara

Oda²,

Yoshidomi³

et al. 1990

J Cereb Blood Flow Metab

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152

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The protective effects of protein kinase inhibitors and a calmodulin kinase inhibitor (W-7) against ischemic neuronal damage were examined in the CA1 subfield of the hippocampus. Staurosporine, KT5720, and KT5822 were used as inhibitors of protein kinase C (PKC), cyclic AMP–dependent protein kinase, and cyclic GMP–dependent protein kinase, respectively. All test compounds were injected topically into the CA1 subfield of the hippocampus. In the gerbil ischemia model, staurosporine (0.1–10 ng) administered 30 min before ischemia prevented neuronal damage in a dose-dependent manner. However, KT5720, KT5822, and W-7 were ineffective, even at a dose of 10 ng. In the rat ischemia model, staurosporine (10 ng) also prevented neuronal damage when administered before ischemic insult, although staurosporine administered 10 or 180 min after recirculation was ineffective. These results suggest the involvement of PKC in CA1 pyramidal cell death after ischemia and that the fate of vulnerable CA1 pyramidal cells through PKC-mediated processes could be determined during the early recirculation period.

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“…, 1984). Hydrolysis of phosphoinositides into di acylglycerol and inositol phosphate after ischemia (Abe et al, 1987) may also enhance PKC activity.…”

Section: Discussionmentioning

confidence: 99%

Staurosporine, a Novel Protein Kinase C Inhibitor, Prevents Postischemic Neuronal Damage in the Gerbil and Rat

Hara

Oda²,

Yoshidomi³

et al. 1990

J Cereb Blood Flow Metab

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152

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“…27 " 29 It is well known that PPIs are rich in arachidonate and stearate. 27 " 29 Therefore, the concomitant increase in the amount of arachidonate and stearate during ischemia has been understood to reflect mainly the breakdown of PPIs during complete or almostcomplete ischemia: Figures 2 and 3). Our results suggest that certain reactions that result in the selective reduction of PEFAs in the MCA occlusion model may exist.…”

Section: Resultsmentioning

confidence: 99%

“…PPIs and FFAs were measured according to the method of Abe et al 27 To ensure complete ischemia, rats lightly anesthetized with ether were decapitated; the brain was immersed in liquid nitrogen immediately (control) or 3 or 6 hours after decapitation. PPIs and FFAs of the cortex of the MCA territory were measured.…”

Section: Methodsmentioning

confidence: 99%

Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger.

Abe

Yuki

Kogure

1988

Stroke

360

189

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Regional changes in the amount of free fatty acids, polyphosphoinositides, and water content in the cerebral cortex were examined using a middle cerebral artery occlusion model of rats. The amount of various free fatty acids increased as polyphosphoinositides decreased during 3 and 6 hours of ischemia in the occluded middle cerebral artery territory. After 3 hours of reperfusion following 3 hours of ischemia, free fatty acids partially recovered while polyphosphoinositides did not. Water content increased significantly after 3 and 6 hours of ischemia, and a further increase was found after 3 hours of reperfusion following 3 hours of ischemia. The change of polyenoic fatty acids in this occluded middle cerebral artery territory was much smaller than that in the case of decapitation ischemia, although the amounts of polyphosphoinositides and monoenoic and saturated fatty acids showed almost identical changes in both cases, probably because polyenoic fatty acids may be washed out and/or peroxidatively consumed in the middle cerebral artery occlusion model due to its residual blood flow. Changes in the area surrounding the occluded middle cerebral artery territory were similar to the above results, although less dramatic However, there was no change in free fatty acids, polyphosphoinositides, and water content in the contralateral cortex. A novel free radical scavenger (MCI-186), which prevents both nonenzymatic peroxidation and lipoxygenase activity in vitro, markedly attenuated the ischemic and postischemk brain swelling. These results suggest that free radical mechanisms may be involved in ischemk and postischemic brain edema. A peroxidative mechanism has been implicated as one of the detrimental factors in ischemic and postischemic brain cell damage. 1 "4 Since Demopoulos 5 indicated the possibility of free radical damage in ischemic brain, various approaches have been tried in an effort to detect some species of oxygen radicals in the ischemic or postischemic brain. However, all attempts have failed to detect oxygen radicals in vivo and in situ because of their short half-lives and/or because of methodologic difficulties involved in trapping and extracting such radicals.*"" Due to the above reasons, only indirect evidence has been obtained indicating the generation of free radicals during and after ischemia. Such evidence includes decreases in ascorbate (reduced form) and ot-tocopherol and an increase in conjugated dienes. 112 -13 Thus, although no radical species have yet been directly detected, it seems to be widely accepted that a certain species of free radicals may exist and may play a role in ischemic and/or postischemic brain damage. 1 ' 5 There are two pathways generating peroxidative reactions in damaged brain as well as in any tissue. One is an auto-oxidation (nonenzymatic peroxidation) and the other is enzyme-processing peroxidation. Nonenzymatic peroxidations have been artificially generated in vitro using brain slices, and they were shown to induce brain swelling. 14 " 17 Cell damage induced by t...

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“…Poly-PI were also degraded Received May 30, 1990; accepted December 13, 1990. following global cerebral ischemia induced by ligation of the common carotid arteries (CCAs) in gerbils. 5 Since these compounds are present in trace quantities in the brain, a more sensitive procedure to study the ischemia-induced breakdown of poly-PI can be achieved by prelabeling the brain with ^Pi 6 -7 or [ 3 H]inositol.…”

mentioning

confidence: 99%

Brain polyphosphoinositide metabolism during focal ischemia in rat cortex.

Lin

Liu

et al. 1991

Stroke

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Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting "Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p<0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two shamoperated controls. However, when 32Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p<0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury. {Stroke 1991;22:495-498)A lthough stimulation of neuronal activity, in-/ \ eluding the process of neurotransmitter re-.Z \ _ lease, is one of the early events of cerebral ischemia, 1 the mechanism leading to irreversible tissue damage is not well understood. A number of neurotransmitters are known to transduce their signals through stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphates (PIFy. In turn, inositol trisphosphates can serve as second messengers for the mobilization of intracellular calcium stores.2 Therefore, stimulation of this cell signaling process may have important consequences toward explaining the alteration of calcium homeostasis underlying ischemic tissue damage.Previous studies by Ikeda et al 3 as well as those from our own laboratory 4 have indicated a rapid decrease in the levels of polyphosphoinositides (poly-PI) in rat brain after global cerebral ischemia induced by decapitation. Poly-PI were also degraded Received May 30, 1990; accepted December 13, 1990. following global cerebral ischemia induced by ligation of the common carotid arteries (CCAs) in gerbils. 5 Since these compounds are present in trace quantities in the brain, a more sensitive procedure to study the ischemia-induced breakdown of poly-PI can be achieved by prelabeling the brain with ^Pi 6 -7 or [ 3 H]inositol.8 Although the tracer technique has been used to examine poly-PI metabolism in a model of global ischemia, the response in brain tissue after a focal ischemic insult has not been examined. We used a rat model of focal cerebral ischemia to examine poly-PI metabolism after ligation of the middle cerebral artery (MCA). This model closely resembles ...

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Mechanism of Arachidonic Acid Liberation During Ischemia in Gerbil Cerebral Cortex

Cited by 267 publications

References 42 publications

Staurosporine, a Novel Protein Kinase C Inhibitor, Prevents Postischemic Neuronal Damage in the Gerbil and Rat

Staurosporine, a Novel Protein Kinase C Inhibitor, Prevents Postischemic Neuronal Damage in the Gerbil and Rat

Strong attenuation of ischemic and postischemic brain edema in rats by a novel free radical scavenger.

Brain polyphosphoinositide metabolism during focal ischemia in rat cortex.

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