Search PubMed⌕ Search

Biomedical subjects

K Kogure

Publications and source records attributed to K Kogure.

At least 271 records · Page 15Linked to original sources
PubMed1991

Induction of amyloid precursor protein mRNA after heat shock in cultured human lymphoblastoid cells.

In an attempt to examine a possible relationship between heat shock stress and an induction of amyloid precursor protein, cultured lymphoblastoid cells established from 12 human subjects were treated with heat shock at 42 degrees C for 30 min. The levels of mRNA for amyloid precursor protein (APP), heat shock protein (HSP) 70, and actin were examined by Northern blot at 1, 3, 8, 24, and 48 h after the heat shock treatment. HSP70 mRNA was induced at 1 and 3 h, and became undetectable again by 8 h. APP mRNA was also induced at 3 and 8 h, and recovered to the steady level by 48 h. No induction was observed in actin mRNA. These results indicate that APP mRNA is induced by heat shock treatment after the induction of HSP70 mRNA, suggesting a role of heat shock response in an induction of APP.

Actins↗
PubMed1991

Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex.

An induction of amyloid precursor protein (APP) mRNA was examined in a middle cerebral artery occlusion model of rats using Northern blot analyses. The level of tubulin mRNA was measured as an internal standard. With persistent focal ischemia, APP mRNA species which contain a Kunitz-type protease inhibitor (KPI) domain were induced in the rat cerebral cortex from 1 to 21 days after the insult with a maximum at 4 days, while total amounts of APP mRNA did not change. No change was observed in the level of tubulin mRNA. These results suggest a selective role of APP species which contain the KPI domain in focal cerebral ischemia.

Alzheimer Disease↗
PubMed1991

Autoradiographic analysis of second messenger and neurotransmitter system receptors in the gerbil hippocampus following transient forebrain ischemia.

Changes in second messenger and neurotransmitter system receptor ligand binding induced by transient forebrain ischemia were studied in the gerbil hippocampus. The animals were allowed variable periods of recovery ranging from 2 h to 7 days after 5-min bilateral carotid artery occlusion. The binding of second messenger systems ([3H]inositol 1,4,5-trisphosphate ([3H]IP3)to inositol 1,4,5-triphosphate, [3H]forskolin to adenylate cyclase and [3H]phorbol 12,13-dibutylate to protein kinase C) and neurotransmitter receptor systems ([3H]PN200-110 to L-type calcium channels. [3H]N6-cyclohexyl-adenosine to adenosine A1 and [3H]quinuclidinyl benzilate to muscarinic cholinergic receptor) were assayed using quantitative autoradiography. In the CA1 subfield, 2 h after ischemia, [3H]IP3, [3H]forskolin, and [3H]quinuclidinyl benzilate binding activities significantly decreased by 25, 17 and 13%, respectively, though no morphological abnormalities were obvious. Six hours after ischemia, the [3H]phorbol 12,13-dibutylate binding activity in the stratum oriens of the CA1 subfield increased by 15%. One day after ischemia, [3H]PN200-110 binding activity in this subfield decreased by 26%, and 7 days after ischemia, [3H]phorbol 12,13-dibutylate and [3H]N6-cyclohexyl-adenosine receptor binding activities decreased in this subfield. In particular, at 7 days after ischemia, [3H]IP3 binding activity in the CA1 subfield showed a complete decline. In the CA3 subfield, [3H]PN200-110 binding activity decreased 2 days after ischemia, and [3H]IP3 and [3H]N6-cyclohexyl-adenosine binding activities decreased 7 days after ischemia. In the dentate gyrus, the structure of which remained histologically intact after ischemic insult, [3H]IP3 and [3H]forskolin binding activities decreased 7 days after ischemia. In contrast, the [3H]phorbol 12,13-dibutylate binding activity increased in the molecular layer of the dentate gyrus 7 days after ischemia. These results indicate that marked alteration of intracellular signal transduction precedes neuronal damage in the hippocampal CA1 subfield and that the histologically intact CA3 and dentate gyrus also shows modulated neuronal transmission after ischemia.

Adenosine↗
PubMed1991

Induction of the 'zinc finger' gene after transient focal ischemia in rat cerebral cortex.

An essential part of gene expression and regulation is the binding of a regulatory protein (transcription factor) to the recognition sequence of the appropriate gene. A novel protein motif for nucleic acid recognition (called 'zinc finger') is one of such transcription factors. A relationship between gene expressions of a transcription factor and heat shock protein (HSP) 70 has been suggested. Possible inductions of mRNA for 'zinc finger' and HSP70 were examined after transient focal ischemia in rat cerebral cortex by Northern blot analysis using a synthetic oligonucleotide probe for 'zinc finger' gene expression, and a human genomic DNA probe for HSP70 gene expression. After 30 min of middle cerebral artery (MCA) occlusion, the rats recovered for 1, 3, 8h, 1, 2, and 7 days (n = 5). Zinc finger gene is normally expressed in rat cerebral cortex, and is induced by transient ischemia with a maximum at 1 h after the reperfusion. In contrast, HSP70 mRNA is not expressed in normal condition, but is greatly induced by transient ischemia with a maximum at 8 h of reperfusion. These results indicate that the gene expression for a transcription factor changes in the early stage of reperfusion after cerebral ischemia before HSP70 induction begins.

Animals↗
PubMed1991

The possible involvement of tetrodotoxin-sensitive ion channels in ischemic neuronal damage in the rat hippocampus.

To determine the role of tetrodotoxin-sensitive ion channels in post-ischemic selective neuronal death, the effect of tetrodotoxin on ischemia-induced brain cell injury was studied in rats. The animals were subjected to 20 min of cerebral ischemia in a four vessels occlusion model. Thirty min before ischemia, tetrodotoxin at a dose of 10(-7) or 10(-6) M was topically applied into the hippocampal CA1 subfield. Morphological changes in the CA1 subfield were evaluated 7 days after ischemia and compared with those of a vehicle-injected group. The average cell density of CA1 pyramidal neurons ipsilateral to the injection (cells/mm, mean +/- S.E.M.) was 27 +/- 7 (n = 6) in the vehicle-treated group, and 56 +/- 13 (n = 6) and 83 +/- 17 (n = 6) in the group treated with tetrodotoxin at doses of 10(-7) and 10(-6) M, respectively. Tetrodotoxin mitigated the ischemic hippocampal neuronal damage in a limited but dose-dependent manner. This suggests that activation of tetrodotoxin-sensitive ion channels might contribute to the process of the ischemic neuronal damage.

Animals↗
PubMed1991

Early loss of astrocytes in herpes simplex virus-induced central nervous system demyelination.

Immunohistochemistry was used to study herpes simplex virus type 1-induced central nervous system demyelination in the trigeminal root entry zone of mice inoculated with herpes simplex virus type 1 by the corneal route. There was no change in peripheral nervous system myelin as shown by immunostaining for P0 glycoprotein. Double immunoperoxidase staining for herpes simplex virus type 1 antigens and glial fibrillary acidic protein showed that most of the infected cells were astrocytes. Glial fibrillary acidic protein immunostaining was completely lost in the inferior medial portion of the trigeminal root entry zone at 6 days after herpes simplex virus type 1 inoculation, a time when central nervous system myelin was preserved as indicated by immunostaining for myelin basic protein. The pattern of glial fibrillary acidic protein staining did not change and herpes simplex virus type 1 antigens were no longer detected after day 8. There was a progressive loss of myelin basic protein staining within the area unstained by glial fibrillary acidic protein antisera on days 8 to 14. This pattern of astrocyte loss before central nervous system demyelination is strikingly different from the reactive astrocytosis seen in other demyelinating lesions, such as acute experimental allergic encephalomyelitis, progressive multifocal leukoencephalopathy, or acute multiple sclerosis. Herpes simplex virus type 1 infection in mice provides an unusual model of acute central nervous system demyelination preceded by a loss of astrocytes.

Animals↗
PubMed1991

Comparative protective effects of vinconate, baclofen, and pentobarbital against neuronal damage following repeated brief cerebral ischemia in the gerbil brain.

We investigated the neuroprotective effects of vinconate (a vinca alkaloid derivative), baclofen (a GABAB receptor agonist), or pentobarbital (a GABAA receptor-effector) on neuronal damage following repeated brief cerebral ischemia in the gerbils. The animals were allowed to survive for 7 days after two or three 2-min ischemic insults induced by bilateral occlusion of the common carotid arteries. Morphological changes were evaluated in hippocampal CA1 sector and selectively vulnerable areas after two or three 2-min ischemic insults at 1-h intervals, respectively. Pretreatment with vinconate significantly reduced histopathological neuronal damage to the hippocampal CA1 sector following two 2-min ischemic insults. However, pretreatment with baclofen and pentobarbital failed to prevent neuronal damage. Pretreatment with vinconate also prevented neuronal damage to the frontal cortex, parietal cortex, and striatum following three 2-min ischemic insults. Nevertheless, this drug failed to prevent neuronal damage to the hippocampal CA1 sector and the thalamus. Results suggest that vinconate, a vica alkaloid derivative, can prevent neuronal damage after repeated brief cerebral ischemia, but not GABAergic agents, such as baclofen and pentobarbital. These findings are of interest in relation to the mechanisms of neuronal damage induced by repeated brief cerebral ischemia.

Animals↗
PubMed1991

Somatosensory evoked potentials following stimulation of median and tibial nerves in patients with localized intracerebral hemorrhage: correlations with clinical and CT findings.

Median and tibial somatosensory evoked potentials (SEPs) were performed on 38 patients with localized intracerebral hemorrhage, 23 with thalamic hemorrhage and 15 with putaminal hemorrhage. Of 65 arms and 62 legs examined, cerebral evoked responses of 60 arms and 50 legs were diagnosed as abnormal. The abnormal findings in scalp-recorded SEPs consisted of a reduction in amplitude, loss of waves and delay in peak latencies. The SEP abnormalities were not indicative of location of hemorrhage. Absence of SEPs was more frequently observed in large hemorrhages and at the early stage. Substantial improvement in SEPs was observed over several months after stroke in many limbs. Motor function as evaluated with Brunnstrom staging of the upper limbs whose SEPs were absent was lower than that whose SEPs were evoked, but that was not observed in the lower limbs because in some cases absence of SEPs coexisted with good motor function. Loss of SEP waves had a significant correlation with disturbed deep sensation. The median and tibial SEPs provided an excellent clinical correlation with the patients' improvement over several months.

Adult↗
PubMed1991

Postischemic alteration of muscarinic acetylcholine, adenosine A1 and calcium antagonist binding sites in selectively vulnerable areas: an autoradiographic study of gerbil brain.

We performed receptor autoradiography to determine sequential alterations in the binding of muscarinic cholinergic and adenosine A1 receptors and of a voltage dependent L-type calcium channel blocker 1 h-1 month after transient cerebral ischemia in the gerbil brain. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyladenosine (CHA) and [3H]PN200-110 were used to label muscarinic and adenosine A1 receptors and L-type calcium channels, respectively. Transient ischemia was induced for 10 min. [3H]QNB and [3H]CHA binding showed no significant alteration in selectively vulnerable areas at an early stage (1-24 h) of recirculation. However, the dentate molecular layer which was resistant to ischemia revealed a significant decrease in the [3H]CHA binding sites 24 h after ischemia. Thereafter, the [3H]QNB and [3H]CHA binding showed significant reduction in most of selectively vulnerable areas. Marked reduction was especially found in the dorsolateral part of striatum and the hippocampal CA1 sector which was the most vulnerable to ischemia. In contrast, [3H]PN200-110 binding showed a transient elevation in the hippocampal CA1 sector, the dentate molecular layer and the thalamus 1 h of recirculation. However, the striatum and neocortex revealed no alteration in the [3H]PN200-110 binding. Thereafter, the reduction in the [3H]PN200-110 binding was seen only in the dorsolateral part of the striatum and the hippocampal CA1 sector. The results suggest that transient cerebral ischemia can cause the alterations in the binding of muscarinic cholinergic and adenosine A1 receptors and of L-type calcium channel blocker in most of selectively vulnerable areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1991

Effects of nerve growth factor and cAMP on expression of acetylcholine receptor in PC12 cells.

The developmental change in acetylcholine-induced current (IACh) was investigated in PC12 cells cultured in the presence or absence of either nerve growth factor (NGF) or 8-Br-cAMP for 10 days. Currents were recorded in the whole-cell mode of the conventional patch-clamp technique. Morphological observations revealed that control cells do not undergo a change in morphology during culture. NGF-treated cells developed long neurites and had dense connections with other cells. 8-Br-cAMP-treated cells developed short neurites, and did not have dense connections. Control cells did not show a change in the mean density of IACh (VH = -80 mV) during the culture period. NGF-treated cells had a maximal increase in the current density of IACh at 5 days after the beginning of treatment, and did not show any further increase until 10 days. 8-Br-cAMP-treated cells had a decrease in current density during the first 6 days, but recovered to the control level after 7 days of treatment. It is concluded that maximal expression of ACh receptors occurs in the relatively early days of development, and that intracellular cAMP does not contribute greatly to their expression.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Mg2+ administered up to twenty-four hours following reperfusion prevents ischemic damage of the Ca1 neurons in the rat hippocampus.

Inductively coupled plasma emission spectrometry analysis was applied to determine ischemia-induced changes of Mg2+ and Ca2+ in vulnerable regions of rat brain. This method can provide an accurate quantification and lower detection limits, as compared to atomic absorption spectrophotometry or several other methods. In the hippocampus, Mg2+ content significantly increases 24 h following 20 min of ischemia, followed by a gradual decrease between 48 and 72 h. Ca2+ accumulation was found at 48 and 72 h. At the cell membrane, Mg2+ plays a role as an endogenous calcium channel blocker of both the receptor-operated and voltage-dependent gates and, in the mitochondria, Mg2+ inhibits Ca2+ uptake processes. We propose that the mobilization of Mg2+ after 24 h reperfusion may counteract the process of ischemia-induced neuronal damage and that decreases of Mg2+ may be correlated with the degree of brain injury. However, in the natural concentration of Mg2+, the counteraction may not be sufficient for a neuroprotective effect. Therefore, after 24 h reperfusion, an artificial enhancement of Mg2+ is necessary for neuroprotection. In order to test the above hypothesis, MgCl2, (50 mM) was administered directly to the CA1 sector of the rat hippocampus before and at various intervals following 20 min of ischemia. Pyramidal cells were evaluated seven days later and neuronal density was determined. Consistent with the hypothesis, a neuroprotective effect was observed, even when MgCl2 was administered 24 h, but not 48 h, after the ischemic episode.

Animals↗
PubMed1991

Involvement of lipid peroxidation and inhibitory mechanisms on ischemic neuronal damage in gerbil hippocampus: quantitative autoradiographic studies on second messenger and neurotransmitter systems.

We investigated, to examine the involvement of lipid peroxidation and inhibitory mechanisms, a novel lipid peroxidation inhibitor (KB-5666) and a GABAA receptor-effector (pentobarbital) on ischemic neuronal damage and the alterations in the second messenger and neurotransmitter systems in Mongolian gerbils by means of morphology and in vitro receptor autoradiography. Quantitative receptor autoradiography visualized binding sites for [3H]inositol 1,4,5-trisphosphate, [3H]forskolin, [3H]phorbol 12,13-dibutyrate, [3H]isradipine (PN200-110), [3H]N6-cyclohexyl-adenosine, and [3H]quinuclidinyl benzilate indicating binding sites for inositol 1,4,5-trisphosphate, forskolin, protein kinase C, L-type calcium channels (or dihydropyridine binding sites), adenosine A1, and muscarinic cholinergic receptors, respectively. In the morphological study, KB-5666, 10 and 50 mg/kg, i.v., 5 min before ischemia, protected against ischemic neuronal damage to the hippocampal CA1 subfield following 5 min of bilateral carotid artery occlusion in a dose-dependent manner. Pentobarbital, 30 mg/kg, i.v., 5 min before ischemia, also had a protective effect. In receptor autoradiographic studies, all receptor bindings decreased significantly in the CA1 subfield seven days after ischemia. In particular, [3H]inositol 1,4,5-trisphosphate binding in the CA1 subfield was completely lost after ischemia. [3H]Inositol 1,4,5-trisphosphate and [3H]forskolin binding decreased as early as 6 h after ischemia. In the CA3 subfield, [3H]inositol 1,4,5-trisphosphate, [3H]PN200-110, and [3H]N6-cyclohexyladenosine bindings decreased seven days after ischemia. In the dentate gyrus, [3H]inositol 1,4,5-trisphosphate binding decreased seven days after ischemia. KB-5666 and pentobarbital prevented reductions in these receptor bindings in the CA1 subfield at 6 h and seven days after ischemia. These results indicate that KB-5666 and pentobarbital protect the brain from both structural and functional damage after ischemia, and that lipid peroxidation and inhibitory mechanisms may play a pivotal role in the neuronal damage of the hippocampal CA1 subfield after ischemia.

Adenosine↗
PubMed1991

Autoradiographic analysis of second-messenger systems in the gerbil hippocampus following repeated brief ischemic insults.

Using [3H]inositol 1,4,5-triphosphate (IP3), [3H]phorbol 12,13-dibutyrate (PDBu) and [3H]forskolin, we performed quantitative autoradiography to determine sequential alterations in second-messenger systems in the gerbil hippocampus following repeated brief ischemic insults. Changes following three 2-min ischemic insults were compared with those following single 2- or 6-min ischemia. [3H]IP3 binding was extremely sensitive to ischemic insult, and more than 80% of the binding sites were lost after destruction of CA1 pyramidal cells following 6-min ischemia and three 2-min ischemic insults. Furthermore, a 30% reduction was observed after 2-min ischemia which leads to no neuronal loss. [3H]PDBu binding in the CA1 subfield decreased by 1 day after three 2-min ischemic insults and by 4 days after 6-min ischemia, and 40-50% reductions were observed at 1 month. In contrast, [3H]forskolin binding was relatively preserved. [3H]PDBu and [3H]forskolin binding transiently increased early in the reperfusion period. We also observed a difference in the pattern and severity of alterations between repeated ischemic insults and single ischemia.

Animals↗
PubMed1991

Unilateral spatial neglect in visual and tactile modalities.

The purpose of this study was to investigate whether a unilateral spatial neglect phenomenon occurs in the tactile modality in the absence of visual information. Ten patients with clinically confirmed visual spatial neglect and 10 normal controls bisected lines visually, or by touch when blindfolded. In visual presentation, the rightward deviation of the subjective midline was significantly more prominent in patients with visual spatial neglect than in normal controls. However, in the tactile tasks, there was no significant difference between the patient group and controls. From these results it was concluded that visual input may play an important role in the occurrence of the unilateral spatial neglect phenomenon.

Adult↗
PubMed1991

Hippocampal damage following repeated brief hypotensive episodes in the rat.

We examined the brain damage following repeated hypotensive episodes in the rat. Severe hypotension was induced by withdrawal of arterial blood. The MABP was maintained at about 25 mm Hg with isoelectric EEG and the shed blood was retransfused. After 1 week of recovery, histopathological changes were examined. No brain damage was observed after 1 min of isoelectric EEG. Mild neuronal damage to the hippocampal CA1 subfield was seen in some animals after two episodes of 1-min isoelectric EEG at a 1-h interval. Significant and consistent neuronal loss in the hippocampal CA1 subfield was observed after three episodes of 1-min isoelectric EEG. Scattered neuronal damage in the thalamus was additionally seen in some animals. The present study indicates that repeated brief hypotensive episodes produce brain damage depending on the number of episodes, even though no brain damage results when induced as a single insult. This animal model may reproduce hemodynamic transient ischemic attacks in humans.

Animals↗
PubMed1991

Prevention of abnormal calcium accumulation in postischemic gerbil brain by vinconate.

We investigated the effect of vinconate on ischemia-induced calcium accumulation in the gerbil brain. The animals were allowed to survive for 7 days after 10 min of ischemia. Abnormal calcium accumulation was evaluated in the gerbil brain after ischemia. Following 10 min ischemia, abnormal calcium accumulation was found in the neocortex, the striatum, the hippocampus, the thalamus, the substantia nigra and the inferior colliculus. Intraperitoneal administration of vinconate (100 mg/kg) immediately after 10 min of ischemia significantly reduced the areas of abnormal calcium accumulation only in the striatum. However, the application of vinconate (100 and 300 mg/kg) 10 min before ischemia dose-dependently decreased the areas of abnormal calcium accumulation in the striatum, the thalamus and the substantia nigra. Morphological observation revealed neuronal damage in the identical sites of the abnormal calcium accumulation. Furthermore, a autoradiographic study using 14C-vinconate showed that this drug easily penetrates the blood-brain barrier and especially localizes in the striatum and the thalamus after 5 min ischemia. The result suggests that vinconate reduces the areas of abnormal calcium accumulation in the postischemic gerbil brain. This effect seems to be mediated via the height distribution in the brain following ischemia.

Animals↗
PubMed1991

Long-term observations on calcium accumulation in postischemic gerbil brain.

We studied delayed postischemic calcium accumulation and neuronal damage in the gerbil brain, using 45Ca autoradiography as a marker for detection of injured tissue and light microscopy. Transient cerebral ischemia was induced for 15 min. Sham-operated gerbils showed no abnormal calcium accumulation and neuronal damage throughout the brain. At 2 and 7 days following 15 min of ischemia, marked calcium accumulation and mild to severe neuronal damage were found in the selectively vulnerable areas such as neocortex, striatum, hippocampus and thalamus, and brainstem such as medial geniculate body, substantia nigra and inferior colliculus. After 1-2 months of recirculation, the calcium accumulation was not recognized in the brainstem. But, the accumulation was still detectable in the striatum, the hippocampus and the thalamus. Morphological study showed that marked proliferation of glia cells was rapid in the inferior colliculus and was relatively slow in the striatum and the hippocampus, although these structures were severely damaged after ischemia. The result suggests that the speed of restoration of injured tissue and the mechanisms for the damage after cerebral ischemia may be different between the selectively vulnerable areas and the brainstem. Furthermore, they suggest that 45Ca autoradiographic technique may provide a useful approach for diagnosis of the restoration of injured tissue at chronic stage following cerebral ischemia.

Animals↗