Biomedical subjects

K Kogure

Publications and source records attributed to K Kogure.

At least 217 records · Page 12Linked to original sources

PubMed1992

Absence of early destructive changes of cytoskeletal proteins after transient ischemia in the rat.

We examined the changes in immunoreactivity of microtubuli-associated protein (MAP) 2 in dendrites by immunohistochemical analysis following 20 min of cerebral ischemia in the rat. A decrease of immunoreactivity of MAP 2 in dendrites in the CA1 subfield of the hippocampus was observed on days 3 and 7 but not on day 1 after ischemia. Early destructive changes of this protein were not observed, a finding which was confirmed by polyacrylamide gel electrophoresis analysis. We elucidated one factor which indicated that destruction of the dendrites of CA1 pyramidal neurons would not take place any earlier than the destruction of the neurons themselves after ischemia in rats.

Animals↗

PubMed1992

Protection of rat hippocampus against ischemic neuronal damage by pretreatment with sublethal ischemia.

We examined whether preconditioning with sublethal ischemia protects against neuronal damage following subsequent lethal ischemic insults. Forebrain ischemia for 3 min in Wistar rats increased heat shock protein-70 immunoreactivity in the hippocampal CA1 subfield but produced no neuronal damage. Preconditioning with 3 min of ischemia followed by 3 days of reperfusion protected against hippocampal CA1 neuronal damage following 6 and 8 min of ischemia but not damage after 10 min of ischemia. The result strongly suggests that stress response induced by sublethal ischemia protects against ischemic brain damage.

Animals↗

PubMed1992

MK-801, but not anisomycin, inhibits the induction of tolerance to ischemia in the gerbil hippocampus.

We examined whether MK-801, an N-methyl-D-aspartate (NMDA)-receptor antagonist, or anisomycin, a reversible protein synthesis inhibitor, inhibits the induction of ischemic tolerance following preconditioning with sublethal ischemia in gerbil hippocampus. Preconditioning with 2 min of ischemia, which induced heat shock protein-72 immunoreactivity, prevented hippocampal CA1 neuronal damage following 3 min of ischemia produced 3 days later. MK-801, but not anisomycin, inhibited the induction of tolerance although the heat shock protein synthesis was reduced in both groups. The present result suggests that NMDA receptor activation, causing stress response, induces the ischemic tolerance.

Animals↗

PubMed1992

Effects of pretreatment with sublethal ischemia on the extracellular glutamate concentrations during secondary ischemia in the gerbil hippocampus evaluated with intracerebral microdialysis.

To elucidate the role of glutamate in the pathogenesis of altered neuronal vulnerability following sublethal ischemia, we measured the extracellular concentrations of glutamate in the gerbil hippocampus using a microdialysis technique. During and immediately after 3-min forebrain ischemia, the extracellular glutamate level showed a striking increase. However, pretreatment with 2-min ischemia 1 h or 4 days before secondary 3-min ischemia did not alter the amount of glutamate released. The result indicates that cumulative damage and tolerance, which take place after pretreatment with sublethal ischemia, are not induced through modification of the amount of glutamate released during secondary ischemia.

Animals↗

PubMed1992

Regional variations in particulate cyclic AMP dependent-protein kinase binding activity in the gerbil hippocampus following transient forebrain ischemia by [3H]cyclic AMP binding.

Changes in the binding of [3H]cyclic AMP as an indicator of particulate cyclic AMP-dependent protein kinase (AMP-DPK) binding activity following transient forebrain ischemia were studied in the gerbil using in vitro autoradiography. [3H]Cyclic AMP binding in the strata pyramidale and lacunosum-moleculare of the hippocampal CA1, the stratum pyramidale of the CA3, and the dentate gyrus decreased transiently in the early postischemic phase but then recovered. However, [3H]cyclic AMP binding in the strata pyramidale and radiatum of the CA1, the granular layer of the dentate gyrus, and the upper layer of the cortex decreased again 7 days after ischemia. In the CA4 subfield and the lower layer of the cortex, the binding showed no significant alterations after ischemia. Administration of pentobarbital prior to the induction of ischemia prevented the decrease in [3H]cyclic AMP binding in the CA1 subfield 6 h and 7 days after ischemia, and showed protective effects against neuronal death of the CA1 pyramidal cells 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield. Furthermore, postischemic reduction of [3H]cyclic AMP binding in the histologically intact cerebral cortex, CA3, and dentate gyrus may be the reflection of cellular dysfunction after energy failure.

Animals↗

PubMed1992

The role of GTP binding proteins in ischemic brain damage: autoradiographic and histopathological study.

Cerebral ischemia produces perturbation of signal transduction systems in neurons. In order to estimate the contribution of guanine nucleotide-binding protein (G-protein) to hippocampal neuronal death, the effect of pertussis toxin (PTX) on the CA1 pyramidal cell damage after transient forebrain ischemia in rats was examined. PTX was administered 3 days before 20 min of transient forebrain ischemia. PTX injection into the CA1 subfield failed to alter the number of ischemic-damaged CA1 pyramidal cells. In contrast, ventricular PTX injection exacerbated CA1 pyramidal cell damage. We also studied postischemic alteration of GTP binding sites in the hippocampal formation using quantitative in vitro autoradiography. Autoradiographic imaging demonstrated predominant distribution of GTP binding sites in synaptic areas in the hippocampus. No significant change of GTP binding activity was observed in the hippocampus until 2 days after recirculation. Seven days after ischemia, when the CA1 pyramidal cells were depleted, the GTP binding sites of the strata oriens and radiatum in the CA1 subfield had reduced by 32% and 31%, respectively. In contrast, GTP binding in the CA3 subfield and the dentate gyrus remained unaltered throughout the reperfusion period. These results suggest that the amount of G-proteins as estimated by GTP binding remained unaltered in the hippocampus during the early recirculation period, when the CA1 pyramidal cells were morphologically intact, and that signal transduction pathways mediated by Gi and Go do not play a major role in delayed death of the CA1 pyramidal cells.

Animals↗

PubMed1992

Decreased expression of neurotrophin-3 mRNA in the rat hippocampus following transient forebrain ischemia.

The expression profile of neurotrophin-3 (NT-3) mRNA in the rat hippocampus after forebrain ischemia was investigated by Northern blot and S1 nuclease protection analyses. The NT-3 transcripts in the hippocampus immediately decreased after ischemic insult, became undetectable within 3 h and remained at undetectable levels for at least 7 days. In contrast, the expression of c-fos and c-jun mRNA transiently increased both in the cerebral cortex and in the hippocampus. These results suggest that brain ischemia triggers dynamic changes in gene expression including a neurotrophic factor, which may cause functional and/or morphological changes of the neuronal network.

Animals↗

PubMed1992

Alteration of dopamine D1 receptor in the strionigral system of the postischemic rat brain.

Chronological changes of dopamine D1 receptor binding were determined in the strionigral system of the rat brain by using [3H]SCH 23390, a highly selective dopamine D1 antagonist, in vitro autoradiography after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. One day after the ischemia, dopamine D1 receptor sites decreased significantly compared with the control value in the lateral segment of the caudate putamen supplied by the occluded MCA. Moreover, 3 days after the ischemia, a significant decrease of dopamine D1 receptor sites was observed in the substantia nigra on the ischemic side which had not been directly affected by the original ischemic insult. The present study indicates that the postischemic delayed reduction of dopamine D1 receptor sites observed in the substantia nigra is due to the degeneration of the dopaminergic nerve terminals in the strionigral system caused by the precedent ischemic damage of the ipsilateral caudate putamen.

Animals↗

PubMed1992

Alterations of 45Ca accumulation and [3H]inositol 1,4,5-trisphosphate binding using autoradiography in the exo-focal postischemic brain areas of the rat.

We studied the alterations of calcium accumulation and intracellular signal transduction using autoradiography of the second messenger system in order to clarify the mechanisms of the delayed neuronal changes in the remote areas of rat brain after transient focal ischemia. Chronological changes of 45Ca accumulation and [3H]inositol 1,4,5-trisphosphate (IP3) binding sites were determined after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. After the ischemic insult, 45Ca accumulation extended to the lateral segment of the caudate putamen and to the cerebral cortex, both supplied by the occluded MCA. One day after the ischemia, [3H]IP3 binding sites decreased significantly compared with the control values in these ischemic areas. Moreover, 3 days after the ischemia, 45Ca accumulation was first detected in the ipsilateral thalamus and the substantia nigra, which lay outside the ischemic areas. In the substantia nigra, a significant decrease of [3H]IP3 binding sites and concurrent 45Ca accumulation were observed. In the thalamus, however, there was not alteration until 1 week after the ischemia, and then [3H]IP3 binding sites increased significantly 2 weeks (P less than 0.05) and 4 weeks (P less than 0.01) after the ischemia. Based on the present study, we speculate that different mechanisms associated with signal transduction systems may be responsible for exo-focal postischemic delayed neuronal changes in the thalamus and the substantia nigra. The increase of [3H]IP3 binding sites of the thalamus in the chronic stage may be new evidence of plasticity related to neurotransmission.

Animals↗

PubMed1992

Autoradiographic analysis of second messenger and neurotransmitter receptor bindings in the strionigral system of the postischemic rat brain.

We studied the postischemic alterations of second messenger and receptor systems focusing on the strionigral pathway in order to clarify the mechanism of the delayed neuronal changes in remote areas of the rat brain after transient focal ischemia. Chronological changes of [3H]forskolin and [3H]SCH 23390 binding sites and 45Ca accumulation were determined by using autoradiographic methods after 90 min of right middle cerebral artery (MCA) occlusion and after such occlusion followed by different periods of recirculation. After the ischemic insult, 45Ca accumulation extended to the lateral segment of the caudate putamen (CPu-L) and to the cerebral cortex, both supplied by the occluded MCA. After the ischemia, [3H]forskolin binding sites were found to be markedly decreased in the early stage in the CPu-L, the ischemic focus in this model, but reduction of the dopamine D-1 receptor sites was first detected there 1 day after the ischemia. On the contrary, in the exo-focal remote areas, there was no alteration of either [3H]forskolin or D-1 receptor binding sites on day 1. However, 3 days after the ischemia, marked reduction of both these binding sites was first observed in the ipsilateral substantia nigra, which had not been directly affected by the original ischemic insult. These postischemic delayed phenomena observed in the substantia nigra developed concurrently with abnormal 45Ca accumulation. These results suggest that strionigral terminal degeneration in the substantia nigra is caused by precedent ischemic damage of the ipsilateral caudate putamen and that intracellular signal transduction including both second messenger and receptor systems may be involved prior to the neuronal damage in the exo-focal postischemic brain areas.

Animals↗

PubMed1992

Phospholipid metabolism and second messenger system after brain ischemia.

To evaluate possible involvement of phospholipid metabolism and related second messenger systems in the selective neuronal damage after ischemia, we measured changes of polyphosphoinositides (PPIs) and free fatty acids (FFAs) in a model of 5-min or 10-min ischemia and reperfusion in gerbils. The binding activity of 3H-phorbol 12,13-dibutyrate (PDBu) for protein kinase C (PKC) and 3H-inositol 1,4,5-triphosphate (IP3) for IP3 receptors was demonstrated autoradiographically. Induction of 70 KDa heat shock protein (HSP70) mRNA and amyloid precursor protein (APP) mRNA was also examined using Northern blot analysis. In the parietal cortex (an area resistant to transient ischemia), PPIs decreased during ischemia and recovered rapidly after reperfusion. However, recovery did not occur in the hippocampal CA1 area (an area more vulnerable to transient ischemia). In the cortex, arachidonic acid (AA) increased during ischemia and returned to baseline by 7 days after reperfusion; in the CA1 area, the AA level remained elevated even after 7 days of reperfusion. PDBu binding decreased in CA1 cells after 2 days of reperfusion. IP3 binding began to decrease at 5 hr of reperfusion, which is far earlier than either the onset of decreased PDBu binding or the observation of neuronal damage by light microscopy. The induction of HSP70 mRNA occurred, but the induction of APP mRNA did not. Regional differences in the induction of HSP70 mRNA were found; CA1 cells produced less HSP70 mRNA than cortical cells 8 hr after transient ischemia. These results suggest that CA1 cell membranes may not recover after transient ischemic attack, and that the membranes of the endoplasmic reticulum, which have IP3 receptors, may undergo alterations earlier than cytoplasmic membranes. The variable induction of HSP70 mRNA may be related to regional differences in vulnerability in cortical and hippocampal CA1 cells after transient ischemia. Involvement of excitatory neurotransmission in the induction of HSP70 has been suggested. The combined data may support a role for inositol phospholipid metabolism, changes in related second messenger systems, and induction of HSP70 in the excitotoxic mechanism of hippocampal CA1 neuronal damage, death, and repair.

Amyloid beta-Protein Precursor↗

PubMed1992

Effect of dilazep dihydrochloride against ischemia and reperfusion-induced disruption of blood-brain barrier in rats: a quantitative study.

The effect of dilazep dihydrochloride (dilazep) against ischemia and reperfusion-induced disruption of blood-brain barrier (BBB) was quantitatively investigated in Slc:Wistar strain rats using Evans blue dye as a BBB destruction indicator. The forebrain of sham-operated animal had a small amount of the dye. A treatment of 3.5-h ischemia plus 2-h reflow extravasated the dye into the brain and markedly increased the dye content as compared with that of sham group (P less than 0.01 vs. sham group). Continuous infusion (i.v.) of dilazep during cerebral ischemia dose-dependently reduced the increase of the dye content, and a significant reduction was found at 3 mg/kg/h (P less than 0.05 vs. control group). Evans blue dye extravasation after ischemia was also greatly reduced in saline-perfused brains by the treatment with dilazep. Dilazep has been reported to inhibit edema formation in cerebral ischemia model of spontaneously hypertensive rats. These results suggest that dilazep prevents the ischemic damage of BBB, which may contribute to reduction of the brain edema.

Animals↗

PubMed1992

Resistance of hippocampal CA-1 noradrenergic fibers to five minutes of transient cerebral ischemia in the gerbil.

We examined changes in the tyrosine hydroxylase (TH)-immunoreactive fibers following 5 min of cerebral ischemia in gerbils using an immunohistochemical method 1, 3 and 30 days after ischemia. Almost all CA-1 pyramidal neurons were lost 3 days after ischemia, whereas noradrenergic fibers were maintained 30 days after ischemia. The present study demonstrated that TH-immunoreactive fibers and cells were resistant to transient ischemia, and that there was no sprouting or hyperactivity in noradrenergic systems after ischemia.

Adrenergic Fibers↗

PubMed1992

Postischemic alteration of muscarinic acetylcholine and adenosine A1 binding sites in gerbil brain. Protective effects of a novel vinca alkaloid derivative, vinconate, and pentobarbital using an autoradiographic study.

We studied the alterations in the binding of muscarinic cholinergic and adenosine A1 receptors following transient cerebral ischemia in Mongolian gerbils and examined the effects of the novel vinca alkaloid derivative vinconate and pentobarbital against the alterations in the binding of these receptors. Animals were allowed to survive for 5 h and 7 days after 10 min of cerebral ischemia induced by bilateral occlusion of common carotid arteries. [3H]Quinuclidinyl benzilate (QNB) and [3H]cyclohexyladenosine (CHA) were used to label muscarinic cholinergic and adenosine A1 receptors, respectively. The [3H]QNB and [3H]CHA bindings showed no significant alteration in the gerbil brain 5 h after ischemia. However, these bindings in the striatum, the hippocampal CA1 sector, and the hippocampal CA3 sector revealed a significant reduction 7 days after ischemia. The [3H]CHA binding also showed a significant decline in the dentate molecular layer 7 days after ischemia. Intraperitoneal application of vinconate (100 and 300 mg/kg) 10 min and pentobarbital (40 mg/kg) 30 min before ischemia showed a mild reduction in the [3H]CHA binding in the brain 5 h after ischemia. Especially, the reduction was found in the hippocampal CA1 sector and the dentate molecular layer. However, the [3H]QNB binding revealed no significant alteration in the brain 5 h after ischemia. Seven days after ischemia, both drugs prevented a marked reduction in the [3H]CHA binding in the striatum, but not in the hippocampal CA1 sector, the hippocampal CA3 sector, and the dentate molecular layer. By contrast, vinconate and pentobarbital failed to prevent the reduction in the [3H]QNB binding in the striatum. Morphological study indicated that vinconate and pentobarbital ameliorated the neuronal damage to the striatum, but not the hippocampal damage 7 days after ischemia. This histological finding was relatively consistent with the alteration in the [3H]CHA binding. These receptor autoradiographic and histological data suggest that vinconate and pentobarbital can protect the brain from both cellular and functional consequences of ischemia. These findings are of interest in relation to the mechanisms of ischemic brain damage.

Animals↗

PubMed1992

Age-related alterations in second-messenger systems in the gerbil brain: autoradiographic analysis and effect of vinconate.

Age-related alterations in binding sites of major second-messenger systems in the gerbil brain were analyzed by receptor autoradiography using [3H]phorbol 12,13-dibutyrate (PDBu), and [3H]inositol 1,4,5-trisphosphate (IP3). In middle-aged gerbils (16 months old), the reduction of PDBu-binding sites was noticed in various brain regions compared with young animals (4 weeks old). By contrast, the elevation of IP3-binding sites was seen in most of brain regions except for the reduction in the cerebellum in the middle-aged animals. Chronic treatment with vinconate partly regulated the age-related changes in the binding sites of these second messengers. The result demonstrates the age-related alterations in the binding sites of an intracellular second-messenger system. Furthermore, they suggest that vinconate partly modulates the age-related alterations in the bindings of second messengers.

Aging↗

PubMed1992

Autoradiographic mapping of neurotransmitter system receptors in mammalian brain.

Regional localization of neurotransmitter system receptors was visualized in the gerbil grain and in the rat brain using receptor autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyladenosine (CHA), [3H]muscimol, [3H]MK-801, [3H]SCH 23390, [3H]PN200-110, [3H]spiperone, and [3H]naloxone were label muscarinic receptors, adenosine A1 receptors, GABAA receptors, N-methyl-D-aspartate (NMDA) receptors, dopamine D1 receptors, L-type calcium channels, spirodecanone receptors, and opioid receptors, respectively. Regional localization of [3H]QNB, [3H]muscimol, [3H]MK-801, [3H]SCH 23390, and [3H]PN200-110 binding sites in the gerbil brain was relatively similar to that in the rat brain. In contrast, the autoradiographic distribution of [3H]spiperone and [3H]naloxone binding sites in the gerbil was quite different from that in the rat. This phenomenon was found especially in the hippocampus and the cerebellum. The results suggest that the gerbil differs from the rat with respect to spirodecanone and opioid binding sites in the hippocampus and the cerebellum. This finding may help to further elucidate the species differences and relationships for brain function and behavioral pharmacology.

Animals↗

PubMed1992

Protective effect of a novel vinca alkaloid derivative, vinconate, against alterations in binding sites of second messengers after transient cerebral ischemia in gerbils.

1. We investigated the alterations in binding sites of three major second messengers, phorbol 12,13-dibutyrate, inositol 1,4,5-trisphosphate and forskolin following transient cerebral ischemia in gerbils, and examined the effects of a novel vinca alkaloid derivative, vinconate against the alterations in the binding of the second messengers following ischemia. 2. Transient cerebral ischemia produced by bilateral occlusion of the common carotid arteries was induced for 10 min, and intraperitoneal administration of vinconate (100 mg/kg and 300 mg/kg) was given 10 min before ischemia. 3. Morphological study indicated that transient ischemia can produce severe neuronal damage in striatum, hippocampal CA1 sector and hippocampal CA3 sector. 4. Transient cerebral ischemia caused the postischemic alterations in the binding of three second messengers. 5. The postischemic alterations in the binding of second messengers were ameliorated by pretreatment with vinconate. This effect was especially observed in the striatum which was most vulnerable to ischemia. 6. These findings are discussed in relation to the mechanism of ischemic neuronal damage.

Animals↗

PubMed1992

Protective effect of vinconate, a novel vinca alkaloid derivative, on glucose utilization and brain edema in a new rat model of middle cerebral artery occlusion.

1. We investigated the effect of a novel vinca alkaloid derivative, vinconate, against brain damage after focal ischemia induced by a middle cerebral artery (MCA) occlusion in rats. 2. Persistent focal ischemia was induced by 6 hr, and vinconate (50 and 100 mg/kg) was given intraperitoneally twice 10 min and 3 hr after MCA occlusion. 3. Focal ischemia produced the disturbance of glucose metabolism, the increase of water content and the impairment of protein synthesis in the surrounding occluded MCA territory. 4. Vinconate was effective in preventing marked reduction of cerebral glucose utilization in the areas surrounding the occluded MCA territory. 5. Vinconate significantly reduced an increase of water content in the surrounding the occluded MCA territory. 6. Preliminary L-[methyl-14C]methionine autoradiographic study also indicated that vinconate can partly prevent a severe impairment of protein synthesis after focal ischemia. 7. The results indicate that vinconate may ameliorate the disturbance of glucose metabolism, brain edema and the impairment of protein synthesis after persistent focal ischemia, and they also suggest that vinconate has a beneficial effect against brain damage.

Animals↗