Origin of intracellular Ca2+ elevation induced by in vitro ischemia-like condition in hippocampal slices

Mitani, Akira; Yanase, Hisato; Sakai, Kimiko; Wake, Y.; Kataoka, Kiyoshi

doi:10.1016/0006-8993(93)91700-3

Cited by 116 publications

(60 citation statements)

References 40 publications

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“…For instance, the duration of in vitro ischemia required to induce astroglial [Ca2+li responses falls within the range that induces anoxic depolarizations (Clark and Rothman, 1987;Grigg and Anderson, 1990;Rader and Lanthorn, 1989) and [Ca2+li increases in neurons (Silver and Erecinska, 1990;Lobner and Lipton, 1993;Mitani et al, 1993). Moreover, ischemic [Ca*+], responses in both astrocytes (reported here) and neurons (Katchman and Hershkowitz, 1993;Lobner and Lipton, 1993;Mitani et al, 1993) involve Ca2+ influx and release from internal stores. The quantitative contribution made by astrocytes to the total tissue [Ca2+li response would depend on the relative volume of the astroglial compartment.…”

Section: Lschemic [Ca*']i Increases In Astrocytes Versus Neuronssupporting

confidence: 50%

In vitro ischemia promotes calcium influx and intracellular calcium release in hippocampal astrocytes

1996

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Section: Lschemic [Ca*']i Increases In Astrocytes Versus Neuronssupporting

confidence: 50%

In vitro ischemia promotes calcium influx and intracellular calcium release in hippocampal astrocytes

1996

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“…These calculations predict a net osmolality gain due to an increase in ion levels of 66 nmol mg-'. Thus the cells will swell during anoxia; this is a documented effect of anoxia in vitro and in vivo (Van Harreveld, Cromwell & Malhotra, 1965;Hansen & Olsen, 1980;Kass & Lipton, 1982 There is evidence that calcium influx is a trigger for anoxic damage (Kass & Lipton, 1982Siesjo, 1988;Roberts & Sick, 1988;Lobner & Lipton, 1993 (Mitani, Yanase, Sakai, Wake & Kataoka, 1993). This is not measured by our technique.…”

Section: Evoked Responsesmentioning

confidence: 79%

“…Thus agents that attenuate the increase in intracellular sodium levels during anoxia, such as lidocaine, may be a major factor in improving cell homeostasis and survival. Indeed, high intracellular sodium has been implicated as leading to the loss of calcium from intracellular organelles which may contribute to high cytoplasmic calcium (Mitani et al 1993). Reduced ATP levels during anoxia, in part due to greater activation of the Na+-K+-ATPase pump, also affect organelle function and may lead to increased cytosolic calcium.…”

Section: Evoked Responsesmentioning

confidence: 99%

The importance of sodium for anoxic transmission damage in rat hippocampal slices: mechanisms of protection by lidocaine.

Fried

Amorim

Chambers

et al. 1995

The Journal of Physiology

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1. The effect of sodium influx on anoxic damage was investigated in rat hippocampal slices.Previous experiments demonstrated that a concentration of tetrodotoxin which blocks neuronal transmission protects against anoxic damage. In this study we examined low concentrations of lidocaine (lignocaine; which do not block neuronal transmission), for their effect on recovery of the evoked population spike recorded from the CAl pyramidal cell layer. 2. Recovery of the population spike, measured 60 min after a 5 min anoxic period, was 4 + 2% of its preanoxic, predrug level. Lidocaine concentrations of 10, 50, and 100 /M significantly improved recovery to 56 + 12, 80 + 7 and 70 + 14 %, respectively. 3. Lidocaine (10 /M) did not alter the size of the evoked response before anoxia and had no significant effect on potassium levels or calcium influx during anoxia. It did, however, reduce cellular sodium levels (146 + 7 vs. 202 + 12 nmol mg-) and preserve ATP levels (2-17 + 0 07 vs. 1-78 + 0 07 nmol mg-1) during anoxia. All values were measured at the end of 5 min of anoxia except those for Ca2+ influx which were measured during 10 min of anoxia. 4. High concentrations of lidocaine (100 /M) did not improve recovery significantly over that observed with 10 jtM. They also had no significantly greater effects on sodium levels than 10/SM lidocaine (137 ± 12 vs. 146 + 7 nmol mg-); however, 100 /M lidocaine significantly improved potassium (202 + 18 vs. 145 + 6 nmol mg-1) and ATP (2-57 + 0-06 vs. 2-17 + 0 07 nmol mg-') levels, while reducing calcium influx (7-76 + 0-12 vs. 9X24 + 0 39 nmol mg-1 (10 min)-1) when compared with 10 /M lidocaine. 5. We conclude that sodium influx and ATP depletion are of major importance in anoxic damage since 10 uM lidocaine reduced these changes during anoxia and improved recovery of the population spike. In addition, our results indicate that the properties of the sodium channel are altered during anoxia, since sodium influx is blocked by a concentration of lidocaine that does not affect the population spike in the preanoxic period.Reduced oxygen delivery to the brain can lead to permanent loss of brain function (Hansen, 1985;Siesjo, 1988). It is important to understand the mechanism of this damage if one is to protect neurons. Studies have implicated calcium

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“…[1][2][3] The elevated intracellular Ca 2ϩ , even that by any route, can bind to Ca 2ϩ -binding proteins, including calmodulin. There is evidence that calmodulin plays a critical role in ischemic brain injury: (1) a persistent increase of Ca 2ϩ -bound calmodulin, which is an active form, after ischemic insults; (2) significant up-regulation of calmodulin gene expression in the CA1 pyramidal cell layer after cerebral ischemia; and (3) protection by calmodulin antagonists against hypoxic/hypoglycemia in organotypic hippocampal cultures.…”

Section: Discussionmentioning

confidence: 99%

“…, where V is the infarct volume of a slice (mm 3 ), 4 is the slice thickness (mm), a is the infarct area (mm 2 ), and b is the infarct area of a slice caudal to the slice (mm 2 ). The infarct volume in the cerebral hemisphere, cortex, or striatum, was calculated by summing the sequential slice injury volumes.…”

Section: Measurement Of Physiological Parametersmentioning

confidence: 99%

DY-9760e, a Calmodulin Antagonist, Reduces Brain Damage after Permanent Focal Cerebral Ischemia in Cats

Sugimura

Takamori

Fukushi

et al. 2005

Biological & Pharmaceutical Bulletin

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Although the cellular pathophysiological mechanisms underlying ischemic brain damage remain to be fully clarified, accumulating evidence suggests that an excessive elevation of intracellular Ca 2ϩ in neurons is a primary mechanism by which cells become injured following cerebral ischemia. 1-3)An overload of Ca 2ϩ in neurons disrupts the ionic balance and activates various Ca 2ϩ -dependent enzymes. Treatment of ischemic animals with compounds that block Ca 2ϩ entry through Ca 2ϩ -permeable channels has been shown to provide protection against the consequences of ischemia in laboratory animals, 4-6) but these treatments have not been found suitable for use in humans. 7-9)Calmodulin is a major Ca 2ϩ -binding protein found mainly in the central nervous system. 10,11) Since many of the pathways through which Ca 2ϩ acts involve Ca 2ϩ /calmodulin signaling systems, including calmodulin-dependent enzymes, inhibition of calmodulin may be a possible alternative approach towards the treatment and prevention of post-ischemic injury. In fact, it has been reported that Ca 2ϩ -bound calmodulin, which is an active form, is increased following ischemia and regional changes correlate with regions of ischemic neuronal damage.12) Furthermore, calmodulin antagonists protect cultured neurons from cell death induced by glutamate, an excitatory amino acid, and protect hippocampal CA1 neurons against hypoxia/hypoglycemia in organotypic cultures. 13,14) DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate) is a calmodulin antagonist that is 2 to 70 times more potent than W-7, a well-known calmodulin antagonist, and can protect neurons against neuronal cell death elicited by Ca 2ϩ overload. [15][16][17] This compound ameliorates brain injury that occurs after transient or permanent focal ischemia and microembolization in rats. [18][19][20][21][22] Although these studies in various rodent models show a hopeful characteristic of DY-9760e, it is subsequently important to assess if it exerts a protective effect in a large animal model of focal cerebral ischemia. Cats, a gyrencephalic species in common with humans, have long been used both in pathophysiological studies for cerebral ischemia and in investigations for the protective efficacy of agents. [23][24][25][26][27] Therefore, the present study was designed to evaluate the potential acute therapeutic effect of DY-9760e on ischemic injury resulting from permanent middle cerebral artery (MCA) occlusion in cats. MATERIALS AND METHODSAnimals Twenty-three male Ico: Fec Eur (Tif) cats (IFFA-CREDO, L'arbresle, France), weighing 2.7 to 3.3 kg, were used in this study. The animals were maintained on canned food (CK, Oriental Yeast, Tokyo, Japan), solid food (NK-C, Nihon Nosan, Yokohama, Japan) and tap water, which were given once a day under a constant 12-h dark-light cycle. All experimental procedures were performed in accordance with the in-house guidelines of the Institutional Animal Care and Use Committee ...

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Origin of intracellular Ca2+ elevation induced by in vitro ischemia-like condition in hippocampal slices

Cited by 116 publications

References 40 publications

In vitro ischemia promotes calcium influx and intracellular calcium release in hippocampal astrocytes

In vitro ischemia promotes calcium influx and intracellular calcium release in hippocampal astrocytes

The importance of sodium for anoxic transmission damage in rat hippocampal slices: mechanisms of protection by lidocaine.

DY-9760e, a Calmodulin Antagonist, Reduces Brain Damage after Permanent Focal Cerebral Ischemia in Cats

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