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K Kogure

Publications and source records attributed to K Kogure.

At least 181 records · Page 10Linked to original sources
PubMed1993

Neuroprotective effect of vinconate against postischemic alterations in binding of [3H]SCH 23390 in the gerbil brain.

1. We investigated alterations in dopamine D1 receptors in the striatum and hippocampus after transient cerebral ischemia in gerbils using [3H]SCH 23390 autoradiography. 2. We also examined the effect of vinconate against the alterations in dopamine D1 receptors after transient ischemia. 3. Transient ischemia was induced for 10 min, and vinconate (100 and 300 mg/kg) was given intraperitoneally 10 min before ischemia. 4. [3H]SCH 23390 binding showed no significant alterations in the striatum and hippocampus 5 hr after ischemia, whereas severe reduction in these areas was found after 7 days of recirculation. 5. Vinconate showed no significant alterations in [3H]SCH 23390 binding in the striatum and hippocampus except for a decrease in the hippocampal CA3 sector and dentate gyrus 5 hr after ischemia. By contrast, vinconate prevented a significant reduction in [3H]SCH 23390 binding in the striatum, hippocampal CA3 sector, hilus, and dentate gyrus 7 days after ischemia. 6. Vinconate inhibited lipid peroxidation in rat brain homogenates in a concentration-related manner. 7. These results indicate that free radicals generated from abnormal dopamine metabolism may play a key role in the development of ischemic brain damage. Furthermore, they suggest that vinconate prevents ischemic brain damage by inhibiting lipid peroxidation.

Animals↗
PubMed1993

Temporal profile of heat shock protein 70 synthesis in ischemic tolerance induced by preconditioning ischemia in rat hippocampus.

We investigated the temporal profile of heat shock protein 70 induction in the rat hippocampus using immunohistochemistry to clarify the mechanism of ischemic tolerance following preconditioning with sublethal ischemia. Although a 6-min period of forebrain ischemia produced severe neuronal damage to the hippocampal CA1 subfield, preconditioning with 3 min of ischemia followed by three days of reperfusion protected against the CA1 neuronal damage after 6 min of ischemia. Immunohistochemical staining against heat shock protein 70 showed that the protein is induced in CA1 pyramidal cells one, three and seven days after 3 min of ischemia, the immunostaining being most intense after three days. Heat shock protein synthesis was observed in CA1, CA3 and dentate hilar neurons one and three days after 6 min of ischemia, both with and without preconditioning. In addition, the heat shock protein was stained in the CA1 2 h and seven days after 6 min of ischemia with preconditioning, but the intensity of staining was relatively weak at these time points. The results suggest that stress response induced by sublethal ischemia protects against ischemic neuronal damage, and that the induced stress response, including heat shock protein 70 synthesis during and immediately after the second ischemic episode, is correlated with the protection because late induction of the heat shock protein did not prevent neuronal death.

Animals↗
PubMed1993

Alterations in [3H]MK-801, [3H]muscimol, [3H]cyclic AMP, and [3H]rolipram binding in the gerbil hippocampus following repeated ischemic insults.

Using [3H]MK-801, [3H]muscimol, [3H]cyclic AMP, and [3H]rolipram, we performed quantitative in vitro autoradiography to determine sequential alterations in the binding of N-methyl-D-aspartate and GABAA receptors, particulate cyclic AMP-dependent protein kinase, and cyclic AMP-selective phosphodiesterase, respectively, in the gerbil hippocampus following repeated brief ischemic insults. Changes from 1 h to 28 days after three 2-min ischemic insults at 1-h intervals were compared with those after 2 and 6 min of ischemia. We observed no alterations in the binding of all the four ligands throughout the observation period following 2 min of ischemia which produced no histological neuronal damage except for transient reductions in [3H]cyclic AMP binding during the early reperfusion period. [3H]Cyclic AMP binding in the CA1 subfield decreased one day after 6 min of ischemia and four days after three 2-min ischemic insults, and 62-65% of the binding was lost after 28 days. [3H]Rolipram binding in the CA1 subfield decreased one day after 6 min of ischemia and the binding was reduced by 45-50% after four and 28 days. Following three 2-min ischemic insults, [3H]rolipram binding decreased in the CA1 at one day, and decreased by 25-33% after 28 days. Both [3H]MK-801 and [3H]muscimol binding was preserved during the early reperfusion period after 6 min of ischemia and three 2-min ischemic insults. Reductions in [3H]MK-801 binding in CA1 were observed four days after ischemic insults when CA1 neuronal destruction was seen. After one month, approximately 50% of [3H]MK-801 binding was lost in CA1 in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1993

Neural grafting to ischemic CA1 lesions in the rat hippocampus: an autoradiographic study.

Fetal hippocampal neurons were stereotaxically transplanted to five-day-old ischemic CA1 lesions in adult rat hippocampi. The recipient brains were examined 14 or 100 days later. The grafts survived well, and transplanted cells usually formed clusters in the host CA1 subfield. In vitro receptor autoradiography was employed to map the following receptors, the ligands indicated in parentheses being used for labeling: muscarinic cholinergic ([3H]quinuclidinyl benzilate), adenosine A1 ([3H]cyclohexyladenosine), kainate ([3H]kainic acid), spirodecanone ([3H]spiperone), opioid ([3H]naloxone), and GABAA ([3H]muscimol). The receptor autoradiographic technique showed significant binding of the six ligands in all hippocampal grafts two weeks after transplantation. One hundred days following transplantation, almost all receptors, especially muscarinic cholinergic, adenosine A1 and opioid receptor bindings in grafts, had significantly increased compared to bindings two weeks after transplantation. At this time, kainate and muscarinic cholinergic receptors in grafts had increased up to the near normal level of the CA1 in the hippocampus. Interestingly, adenosine A1 receptors in the grafted side had significantly increased not only in the CA1 but also in the stratum oriens of the CA3 compared with that in the non-grafted side. The increase of [3H]quinuclidinyl benzilate binding corresponded well with the innervation of acetylcholinesterase-positive fibers at 100 days after grafting. These results demonstrate that the transplanted neurons, which showed both pre- and post-synaptic autoradiographic markers in the ischemic CA1 lesions, are able to develop their properties and express the nature of normal hippocampal neurons.

Acetylcholinesterase↗
PubMed1993

Coordinated expression of messenger RNAs for nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in the rat hippocampus following transient forebrain ischemia.

Changes in nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 messenger RNA expression in the rat hippocampus following 20 min of transient forebrain ischemia were evaluated using Northern blot analysis and in situ hybridization histochemistry. Twelve hours after the insult, the level of nerve growth factor messenger RNA increased markedly in the granular cell layer of the dentate gyrus and by day 2 returned to control levels. The level of brain-derived neurotrophic factor messenger RNA showed a persistent and moderate increase. The highest expression of brain-derived neurotrophic factor messenger RNA was seen in the dentate granule cells on day 2 after the insult, and then the expression returned to the control levels. At 2 days post-ischemia, contents of messenger RNAs for nerve growth factor and brain-derived neurotrophic factor were reduced in the CA1 region, which may represent delayed loss of vulnerable CA1 pyramidal neurons. In contrast to brain-derived neurotrophic factor and nerve growth factor messenger RNA expression, the level of neurotrophin-3 messenger RNA declined in the CA1, the CA2 and the dentate granular layer immediately after ischemic insult. In the CA1 region, the reduced expression persisted for at least seven days, but in the dentate gyrus, neurotrophin-3 messenger RNA expression returned to the control levels after two days of post-ischemic recovery. These results suggest that nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 genes are differentially regulated and that each of their gene products may play different roles in the central nervous system under pathophysiological conditions.

Animals↗
PubMed1993

Postischemic changes of intracellular second messengers in the gerbil brain after long-term survival: an autoradiographic study.

Receptor autoradiographic and histological techniques were used to investigate the long-term changes that occur in the gerbil brain following the induction of transient cerebral ischemia. Transient ischemia was induced for 3 and 10 min, and animals were allowed to survive for eight months. Autoradiographic analysis of second messenger systems showed that 3-min ischemia caused a significant reduction in [3H]inositol-1,4,5-trisphosphate binding in the hippocampal CA1 sector, whereas the alteration in [3H]phorbol 12,13-dibutyrate, [3H]forskolin and [3H] cyclic-AMP bindings was not found in this region. In the striatum, 3-min ischemia caused no significant alteration in [3H]phorbol 12,13-dibutyrate, [3H]inositol-1,4,5-trisphosphate and [3H]forskolin binding sites, whereas the [3H]cyclic-AMP binding showed a significant elevation. The thalamus exhibited a significant elevation only in the [3H]inositol-1,4,5-trisphosphate binding sites. Following 10-min ischemia, [3H]phorbol 12,13-dibutyrate, [3H]inositol-1,4,5-trisphosphate and [3H]cyclic-AMP binding sites revealed a significant reduction in the hippocampus, whereas the [3H]forskolin binding showed a significant elevation in this area. In the striatum, 10-min ischemia caused no significant alteration in [3H]phorbol 12,13-dibutyrate, [3H]inositol-1,4,5-trisphosphate and [3H]cyclic-AMP binding sites. However, marked reduction in the [3H]forskolin binding was seen in the striatum. Furthermore, the substantia nigra also exhibited a significant reduction in [3H]forskolin binding. Histological studies suggested that 3-min ischemia can produce severe neuronal damage and mild shrinkage to the hippocampal CA1 sector. They also showed that 10-min ischemia can cause severe tissue shrinkage and severe neuronal damage in the hippocampal CA1 sector and hippocampal CA3 sector. Thus, the hippocampal damage following ischemia was not static but progressive.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Sequential alteration of [3H]rolipram binding in gerbil brain after transient cerebral ischemia.

The time course of rolipram (Ca2+/calmodulin independent cyclic adenosine monophosphate inhibitor) binding sites changes following gerbil transient forebrain ischemia was determined using receptor autoradiography. Gerbils subjected to 10-min ischemia revealed a significant reduction in rolipram binding in most selectively vulnerable regions early in the recirculation (1-5 h). Marked reduction in the rolipram binding was seen in the selectively vulnerable areas 48 h or 7 days after ischemia. Thereafter, the rolipram binding in the hippocampal CA1 and CA3 sectors, which were most vulnerable to ischemia, was severely reduced up to 1 month after recirculation. In contrast, the reduction of the rolipram binding activity in other regions recovered to sham-operated level or showed a slight recovery. Interestingly, the dentate gyrus, which was resistant to ischemia, also exhibited a significant reduction of the rolipram binding activity up to 1 month after ischemia. Eight months after ischemia, the hippocampal CA1 and CA3 sectors showed severe shrinkage and marked reduction in the rolipram binding. Other regions exhibited no significant reduction in the rolipram binding except for a slight reduction in the thalamus. These results demonstrate that transient cerebral ischemia causes severe reduction in rolipram binding sites in selectively vulnerable areas, and this reduction precedes the neuronal cell loss. These findings may reflect the alteration of an intracellular phosphodiesterase activity after ischemia.

Animals↗
PubMed1993

Spermine accelerates iron-induced lipid peroxidation in mitochondria by modification of membrane surface charge.

The polyamine spermine was found to make the mitochondrial membrane more susceptible to lipid peroxidation induced by adenosine 5'-diphosphate (ADP)/Fe2+. It shortened the lag time before induction of peroxidation, but did not affect the rate of lipid peroxidation. It had no effect on lipid peroxidation of electrically neutral egg yolk phosphatidylcholine liposomes, but had an effect on lipid peroxidation of negatively charged liposomes consisting of egg yolk phosphatidylcholine and bovine heart cardiolipin similar to that on peroxidation in mitochondria. Spermine decreased the negative zeta-potential of these negatively charged liposomes consisting of phosphatidylcholine and cardiolipin. These results suggest that the hydrophilic polycation spermine reduces the negative charge on the surface of mitochondrial membrane, possibly by its interaction with negatively charged polar heads of phospholipids, and that this neutralization of the surface charge renders the mitochondrial membrane more susceptible to induction of lipid peroxidation induced by ADP/Fe2+.

Adenosine Diphosphate↗
PubMed1993

Changes of mitochondrial DNA and heat shock protein gene expressions in gerbil hippocampus after transient forebrain ischemia.

Hippocampal CA1 neurons are the most vulnerable to transient cerebral ischemia. However, the mechanism has not been fully understood. The level of mRNA for cytochrome C oxidase (COX) subunit I (COX-I), which is encoded by mitochondrial (mt) DNA, progressively decreased in the hippocampal CA1 neurons of gerbils from 3 h of reperfusion after 3.5 min of transient forebrain ischemia and completely disappeared at 7 days. The activity of COX protein also showed an early decrease in CA1 cells and was followed by reduction of the level of COX-I DNA after 2 days. However, succinic dehydrogenase, an mt enzyme encoded by nuclear DNA, maintained normal activity until 1 day in the CA1 cells and significantly decreased at 7 days. The mRNA for mt heat shock protein (HSP) 60 began to increase at 3 h in the CA1 cells and was sustained until 1 day. The mRNAs for 72-kDa heat shock protein and 73-kDa heat shock cognate protein, which are located mainly in the cytoplasm, were induced together in the CA1 cells with a peak at 1-2 days. These results suggest that a disturbance of mt DNA expression occurred in the CA1 neurons at the early stage of reperfusion and was aggravated over the course of time. The disturbance could cause progressive failure of energy production of the cells that eventually results in neuronal cell death.

Animals↗
PubMed1993

Acceleration of HSP70 and HSC70 heat shock gene expression following transient ischemia in the preconditioned gerbil hippocampus.

To evaluate the mechanism of tolerance to ischemia, inductions of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs in gerbil hippocampus were compared with in situ hybridization between cases of a single 3.5-min period of forebrain ischemia and a 3.5-min period of ischemia 2 days after 2-min pretreatment with ischemia. Immunohistochemistry for HSP70 protein and morphological studies were also performed in the same brains up to 7 days after the reperfusion. Following a single 3.5-min period of ischemia, HSP70 and HSC70 mRNAs were induced in all hippocampal cells. However, the hippocampal CA1 cells produced only a minimum of HSP70 protein, and the cells were almost lost by 7 days. Following 3.5 min of ischemia after 2-min pretreatment, large populations of the CA1 cells survived at 7 days. The peak time of the HSP70 and HSC70 mRNA induction shifted to an earlier period of reperfusion in all hippocampal cells as compared with the case of a single episode of ischemia. The peak of HSP70 and HSC70 mRNA induction shifted from 1 day to 3 h in the CA1 cells. The CA1 cells produced strongly immunoreactive HSP70 from 3 hr to 2 days. These results suggest that pretreatment with an initial period of ischemia (for 2 min) accelerated HSP70 and HSC70 gene expression at the transcriptional level, ameliorated the translational disturbance of HSP70 mRNA to protein, and saved the CA1 cells from subsequent lethal ischemia (for 3.5 min). These changes of heat shock gene expression might play important roles in the acquisition of ischemic tolerance of hippocampal CA1 neurons.

Animals↗
PubMed1993

Isolation and expression of an ischaemia-induced gene from gerbil cerebral cortex by subtractive hybridization.

A subtraction cDNA library was made using subtractive hybridization of cDNA libraries constructed from gerbil cerebral cortex of control animals and animals 8 h after 10 min of transient forebrain ischaemia. After differential screening, a cDNA clone (named pGSH3) was isolated as a gene which is expressed only after the ischaemia insult. The cDNA insert of pGSH3 (0.7 Kb) hybridized to 2.8 Kb mRNA of ischaemic cerebral cortex. The gene was normally expressed in a small amount in the cerebellum, kidney, and lung, but was not expressed in the cerebral cortex, heart, liver, or jejunum in a detectable amount. Eight hours after the 10-min transient forebrain ischaemia, the gene expression became prominent in the cerebral cortex, and the amount of the mRNA also increased in the lung and kidney. An analysis of DNA sequence revealed that the pGSH3 insert has a 91.3 per cent homology with a 70-Kd human heat shock protein (HSP70) gene. These results indicate that an ischaemia-induced gene was isolated as a cDNA clone (pGSH3) by subtractive hybridization and differential screening. Expression of the gene was first detected in other organs especially in the kidney and lung after transient forebrain ischaemia.

Animals↗
PubMed1993

Inhibition of ischaemic tolerance in the gerbil hippocampus by quercetin and anti-heat shock protein-70 antibody.

To clarify the role of heat shock protein-70 (HSP70) in ischaemic tolerance following pretreatment with sublethal cerebral ischaemia, we examined whether the induction of tolerance in the gerbil hippocampus is inhibited by quercetin, an inhibitor of HSP70 expression, or anti-HSP70 antibody. A 3 min period of forebrain ischaemia was induced following pretreatment with 2 min of ischaemia and 3 days of reperfusion. Quercetin or anti-HSP70 antibody was continuously infused into the left lateral ventricle using an implanted osmotic minipump started 3 h after or 2 h before the first ischaemia. The animals were killed 4 days after the second ischaemia for histological observations. Both agents produced no neuronal damage in the brain following a single 2 min period of ischaemia. The neuronal density of the CA1 hippocampus in animals subjected to treatment with quercetin and anti-HSP70 antibody was significantly lower than vehicle-treated animals but were significantly higher than animals with a single 3 min period of ischaemia. Thus, the present study showed that quercetin and anti-HSP70 antibody prevent the induction of ischaemic tolerance. The result suggests that HSP70 expression, at least in part, plays a role in the induction of ischaemic tolerance.

Animals↗
PubMed1993

Reduction of HSP70 and HSC70 heat shock mRNA induction by pentobarbital after transient global ischemia in gerbil brain.

The effect of pentobarbital on the induction of heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 mRNAs after transient global ischemia in gerbil brains was investigated by in situ hybridization using cloned cDNA probes selective for each mRNA species. In sham control brains, HSP70 mRNA was scarcely present, whereas HSC70 mRNA was present in most cell populations. After a 5-min occlusion of bilateral common carotid arteries, HSP70 and HSC70 mRNAs were induced together in several cells and were especially dense in hippocampal dentate granule cells at 3 h, but the strong hybridization of the mRNAs continued only in hippocampal CA1 cells by 2 days. At 7 days after the ischemia, CA1 neuronal cell death was apparent, and the HSP70 mRNA disappeared and HSC70 mRNA content returned to the sham level, except for in the CA1 cells. Pretreatment with pentobarbital (40 mg/kg, i.p.) greatly reduced or inhibited the induction of HSP70 and HSC70 mRNAs at both early (3-h) and late (2-day) phases after ischemia. The drug also prevented CA1 cell death at 7 days along with the maintenance of expression of HSC70 mRNA at the sham control level. Hypothermic effects of pentobarbital were noted at 30 and 60 min after the reperfusion, whereas at 2 h there was no statistical significance between the control and drug-treated groups. The great reduction of HSP70 and HSC70 mRNA induction at both early and late phases after ischemia suggests that pentobarbital reduces intra-and/or postischemic stress and may protect CA1 cells from ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Sequential changes of [3H]cyclic AMP binding in the gerbil brain following transient cerebral ischaemia.

Sequential alterations in the binding of [3H]cyclic AMP (cAMP) as an indicator of cAMP-dependent protein kinase (cAMP-DPK) binding activity following transient cerebral ischaemia were studied in the gerbil brain using receptor autoradiography. Transient ischaemia was induced for 10 min. [3H]cAMP binding in the stratum oriens and pyramidale of the hippocampal CA1 sector significantly decreased in the early post-ischaemic stage and showed severe reduction 7 days and 1 month after recirculation. By contrast, [3H]cAMP binding showed no significant alterations in the stratum radiatum of the hippocampal CA1 sector and the stratum pyramidale of the hippocampal CA3 sector up to 48 h after ischaemia. However, the binding in these areas significantly decreased 7 days and 1 month after ischaemia. The stratum lacunosum-moleculare of the hippocampal CA1 sector and dentate gyrus showed no significant changes in [3H]cAMP binding throughout the recirculation period. However, in the dorsolateral part of the striatum, where severe neuronal damage was seen morphologically, [3H]cAMP binding was significantly reduced only one month after ischaemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 sector, but not in the striatum. Furthermore, our autoradiographic data suggest that post-ischaemic alteration in [3H]cAMP binding between the hippocampal CA1 sector and striatum may be produced by different mechanisms.

Animals↗
PubMed1993

Presence of tetrodotoxin and tetrodotoxin-producing bacteria in freshwater sediments.

The occurrence of tetrodotoxin (TTX) in sediment from Lake Suwa, Japan, was confirmed by a tissue culture assay, high-performance liquid chromatography, and gas chromatography-mass spectrometry. Altogether, 17 TTX-producing bacteria belonging to five genera were isolated from Lake Suwa and Pond Inokasira. Our results indicate that TTX and TTX-producing bacteria occur even in freshwater environments.

Journal Article↗