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K Kogure

Publications and source records attributed to K Kogure.

At least 73 records · Page 4Linked to original sources
PubMed1996

Temporal profile of nerve growth factor-like immunoreactivity after transient focal cerebral ischemia in rats.

We studied the temporal profile of nerve growth factor-like immunoreactivity (NGF-LI) in the rat brains following 30 min of middle cerebral artery occlusion. The rats were decapitated at 4 h, 1, 3, 7, and 14 days of recirculation. Brain sections at the level of striatum were immunostained against NGF as well as a stress protein, HSP70. Also, double immunostaining of NGF and glial fibrillary acidic protein was performed. In the sham-control rats, NGF-LI was normally present in the cortical and striatal neurons. However, at 4 h of recirculation, there was a significant decrease of NGF-LI in the ischemic cortex and striatum. From 1 day, NGF-LI was absent completely in the ischemic striatum. However, in the ischemic cortex, NGF-LI decreased to the lowest level at 1 day, but it recovered gradually from 3 days and increased significantly to above sham-control level at 7 days. At 14 days of recirculation, NGF-LI returned to a near sham-control level. In the non-ischemic cortex, NGF-LI increased gradually from 4 h with a peak at 7 days, and returned to the sham-control level at 14 days of recirculation. A HSP70 was induced in the ischemic cortex at 1 and 3 days, when there was a significant reduction of NGF-LI. The number of reactive astrocytes increased gradually and NGF-LI in the reactive astrocytes became gradually intense after ischemia. The present finding showing that NGF-LI can be recovered in the stressed cortical neurons suggests a possible involvement of NGF in the process of neuronal survival after focal cerebral ischemia. The expression of NGF in reactive astrocytes indicates that astrocyte may also play a role in supporting neuronal survival after ischemia.

Animals↗
PubMed1996

Regional difference in induction of heme oxygenase-1 protein following rat transient forebrain ischemia.

Heme oxygenase (HO) is a rate-limiting enzyme in heme catabolism, the end products of which include iron, carbon monoxide and bilirubin. We investigated the changes in expression of an inducible form, heme oxygenase-1 (HO-1), and a constitutive form, HO-2, in rat brain following 20 min of forebrain ischemia, using specific antisera for HO-1 and HO-2. HO-1 protein was remarkably induced in brain following ischemia, while the level of HO-2 protein was not noticeably affected. The level of HO-1 protein expression was maximal at 12 h, which is in good agreement with the time course of the HO-1 mRNA induction. In the cortical mantle, most of the cells expressing increased HO-1 protein were identified as pyramidal neurons and astrocytes by their shapes and locations. In hippocampal CA-2 and CA-3 subfields, prominent induction was observed in astrocytes rather than in neuronal cells. By contrast, the HO-1 protein was not detected in the CA1 subfield following the insult, although the increased level of transcripts was evident in neurons and glial cells. These results suggest that not only in neuronal cells but also in astrocytes within the CA1 subfield, there may be an impairment of protein metabolism, preceding the delayed CA1 pyramidal cell losses.

Animals↗
PubMed1996

Role of platelet-activating factor and thromboxane A2 in radical production during ischemia and reperfusion of the rat brain.

Oxygen radicals produced by activated neutrophils have been involved in brain injury during ischemia-reperfusion. Platelet-activating factor (PAF) is a candidate as one of the mediators of neutrophil activation during cerebral ischemia-reperfusion. Recent evidence indicates that PAF-induced neutrophil activation is mediated by thromboxane A2 (TXA2). To study the role of PAF and TXA2 in radical production during cerebral ischemia-reperfusion, we evaluated the effects of a PAF antagonist, Y-24180, and a TXA2 antagonist, S-1452, on radical formation in rats with 1 h middle cerebral artery (MCA) occlusion. In the present study, we employed a new electron spin resonance (ESR) method coupled with brain microdialysis. The method uses the endogenous ascorbyl radical (AR) concentration as a marker of oxygen radicals and requires no spin-trapping agents. In the vehicle controls, extracellular AR from the ischemic brain cortex decreased during MCA occlusion. Following reperfusion, AR significantly increased at 30 mm and 1 h, returned to near the basal levels at 2 h, and increased again at 24 h after reperfusion. In the rats treated with S-1452 or Y-24180, AR decreased during MCA occlusion to the same extent as in the vehicle control. However, pretreatment with Y-24180 or S-1452 significantly attenuated the increase in extracellular AR after reperfusion, while it exerted no effect on the changes in extracellular ascorbate or tissue pO2 throughout the experimental period. In conclusion, PAF and TXA2 might contribute to cerebral ischemia-reperfusion injury by increasing the generation of oxygen radicals.

Animals↗
PubMed1996

Intravenous administration of follistatin: delivery to the liver and effect on liver regeneration after partial hepatectomy.

When 1 microgram 125I-follistatin was administered into a rat intravenously, radioactivity levels in serum decreased rapidly. Analysis with a biexponential equation showed that the initial half-life and the terminal half-life were 4.0 and 130.8 minutes, respectively. After 2 hours of infusion, approximately 9% of the follistatin infused remained in the liver, which was much more than that in kidney, spleen, pancreas, intestine, or lung. Autoradiography of the liver obtained at 24 hours of infusion revealed that numerous grains were located in parenchymal cells. Radioactivity of 125I-follistatin in the liver remained elevated until 72 hours and declined markedly thereafter. When a booster shot of 125I-follistatin was administered at 72 hours, radioactivity in the liver at 120 hours was markedly increased compared with that in rats that received a single shot of 125I-follistatin. We then examined the effect of intravenous infusion of follistatin on liver regeneration after hepatectomy of 70%. Immediately after the hepatectomy, either 1 microgram follistatin or saline was infused intravenously. In some rats, a booster shot was infused at 72 hours. After 120 hours of hepatectomy of 70%, remnant liver weight, liver regeneration rate, and DNA content were significantly (P < .05) higher in rats that received a booster shot of follistatin at 72 hours than those in control rats. These results indicate that follistatin administered intravenously accumulates in the liver and promotes liver regeneration after partial hepatectomy.

Animals↗
PubMed1996

Inflammation of the brain after ischemia.

Cytokines which promote emigration of leukocytes from the vascular lumen into the injured brain tissue are produced at the site of incipient cerebral infarction. The blood-borne invaders then accelerate the decomposition of brain cells by their toxic by-products, phagocytic action, and by the immune reaction. Recently accumulated data in our laboratories and other research facilities show that depleting the amount of circulating leukocytes or administering anti-inflammatory chemicals such as cytokine blocking agents, anti-adhesion molecule antibodies, and immunosuppressants effectively minimize the size of ischemia induced cerebral infarction. Based on the fact the leukocyte invasion of the affected brain tissue occurs 6 to 24 hours after onset of ischemia, administration of an anti-inflammatory therapy may widen the therapeutic window against stroke.

Acute-Phase Reaction↗
PubMed1996

A biological method for the quantitative measurement of tetrodotoxin (TTX): tissue culture bioassay in combination with a water-soluble tetrazolium salt.

A tissue culture bioassay, using the mouse neuroblastoma cell line (Neuro2A), was improved to provide a simple and sensitive bioassay for TTX or sodium channel-blocking toxins (SCB). The water-soluble tetrazolium salt, 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetraz olium, monosodium salt (WST-1), was applied to replace the time-consuming and subjective cell-counting procedure of the cells with automatic measurement, using a microplate reader. It was also confirmed that this method is directly applicable to bacterial culture supernatants, with the precaution of possible interference.

Animals↗
PubMed1996

Behavioral studies on rats with transient cerebral ischemia induced by occlusion of the middle cerebral artery.

The behavioral effects of transient cerebral ischemia in adult Wistar rats were studied. In Experiment 1, rats were subjected to 90-min occlusion of the unilateral, left or right, middle cerebral artery (MCA) followed by recirculation. The locomotor activity had not changed 3 and 30 days after the occlusion, except that the number of rearing was significantly decreased by left MCA occlusion. Rats were examined in a radial maze system for learning and memory ability during 4 weeks from the 3rd day after ischemia (the 3rd day was counted as day 1 of the experiment). Maze performance was slightly disturbed due to focal brain damage by MCA occlusion, but the disturbance was statistically significant only on days 6, 11, and 15 in the right occlusion. In Experiment 2, rats were trained to master a radial maze task completely for 4 weeks, and then subjected to transient unilateral (right) ischemia as described above. These rats showed an increase in incorrect entry in the radial maze task from day 4 to day 14. However, on day 21, the number of incorrect entry decreased to the control level of the sham-operated group. The numbers of correct choice were inversely related with those of incorrect entry, though slightly blunted. Coincidentally, the time required to solve the maze task was also prolonged from day 4 to day 14, but returned to the control time on day 21. These results suggest that unilateral ischemia transiently suppresses both acquiring radial maze performance and maintenance of learned performance and that it is a good model for studying human focal cerebral ischemia.

Adult↗
PubMed1996

Involvement of cytokine production in pathogenesis of transient cerebral ischemic damage.

The contribution of cytokines in an inflammatory cascade on cerebral reperfusion injury are characterized as typical phases; leukocytes invision, microglial activation, and remodeling. Within 1-2 days, IL-1 (interleukin-1) and TNF (tumour necrosis factor) induce the expression of adhesion molecules that cause leukocytes adhere to endothelial cells. IL-8 (CINC; cytokine-induced neutrophil chemoattractant) is a well-known chemokine that promotes invasion of these leukocytes into brain parenchyma. The activation of proteases and free radical formation by invading neutrophils induces lipid peroxidation and subsequently neuronal damage. From 2 to 7 days, microglia is activated mainly in the "reactive zone" at the boundary of the infarct, and secrete IL-1 and TNF. These cytokines induce astroglial proliferation and production of trophic factors by astroglia to limit the neuronal damage. However, excess astrogliosis exert a negative effect on neuroregeneration. From 7 to 30 days, phagocytic macrophages are observed in the core of infarction sites. The macrophages release a number of cytophylactic agents including proteases and superoxide anions to degrade the damaged areas. TGF-beta and basic FGF (fibroblast growth factor) from glial cells and macrophages induce angiogenesis to discard the debris for subsequent remodeling. These complicated cascade after cerebral reperfusion injury are indeed controlled by cytokines: IL-1 and TNF are considered to be primary mediators that work in concert with IL-8 and growth factors to initiate and regulate the local inflammation in the brain.

Animals↗
PubMed1996

Inflammatory reaction after brain damage and prospective therapy against damage impending cerebral infarction.

Cytokines which promote emigration of leukocytes from the vascular lumen into the injured brain tissue are produced at the site of incipient cerebral infarction. The blood-borne invaders then accelerate the decomposition of brain cells by their toxic by-products, phagocytic action, and by the immune reaction. Recently accumulated data in our laboratories and other research facilities show that depleting the amount of circulating leukocytes or administering anti-inflammatory chemicals such as cytokine blocking agents, anti-adhesion molecule antibodies, and immunosuppressants effectively minimize the size of ischemia induced cerebral infarction. Based on the fact that leukocyte invasion of the affected brain tissue occurs 6 to 24 hours after onset of ischemia, administration of an anti-inflammatory therapy may widen the therapeutic window against stroke.

Animals↗
PubMed1996

[Resolution of psoriasis vulgaris following allogeneic bone marrow transplantation for aplastic anemia].

A 36 year-old man had suffered from psoriasis vulgaris for about 25 years. He had received corticosteroids ointment and PUVA therapy with partial response. In 1987, he was diagnosed as having aplastic anemia (AA) and treated with various medications, but failed to respond. He received an allogeneic bone marrow transplantation (BMT) from his histocompatible sister in 1993. Conditioning regimen of BMT consisted of total lymphoid irradiation (7.5 Gy) and cyclophosphamide (200 mg/kg). Cyclosporin A and methotrexate were given for prophylaxis of graft-versus-host disease. On day 24, bone marrow examination disclosed normocellular marrow and karyotypic analysis completely confirmed the donor's origin. Before BMT, he had systemic psoriatic plaques with scales, together with nail involvement. After BMT, psoriatic plaques disappeared and nail deformity improved. He has remained in remission of his AA and completely free of psoriasis in the absence of immunosuppressive or other treatments. The cause of psoriasis is thought to be an immune-mediated disorder. Our case supports the observation that changing the host's immune system through allogeneic BMT can achieve remission of psoriasis. It is suggested that allogeneic BMT may be one strategy for the treatment of intractable immune-mediated disorders.

Adult↗
PubMed1996

Isolation of an ischemia-induced gene and early disturbance of mitochondrial DNA expression after transient forebrain ischemia.

A subtraction cDNA library was made using subtractive hybridization of cDNA libraries constructed from gerbil cerebral cortex of control animals and animals 8 hours after a 10-min transient forebrain ischemia. After differential screening, a cDNA clone (named pGSH3) was isolated as a gene that is expressed only after the ischemic insult. The cDNA insert of pGSH3 (0.7 kb) hybridized to the 2.8-kb mRNA of ischemic 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 ischemia, 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% homology with a 72-kd human heat-shock protein (hsp70) gene. These results indicate that an ischemia-induced gene was isolated as a cDNA clone (pGSH3) by subreactive hybridization and differential screening. Expression of the gene was detected in other organs especially in the kidney and lung 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 subunit I (COX-I), which is encoded by mitochondrial DNA (mtDNA), progressively deceased in the hippocampal CA1 neurons of gerbils from 3 hours of the reperfusion after 3.5 min of transient forebrain ischemia, and completely disappeared at 7 days. The activity of cytochrome C oxidase (COX) protein also showed the early decrease in the CA1 cells, and was followed by the reduction of the level of COX-I DNA after 2 days. However, the activity of succinic dehydrogenase (SDH), a mitochondrial enzyme that is encoded by nuclear DNA, maintained normal activity until day 1 in the CA1 cells, and significantly decreased at 7 days. The mRNA for mitochondrial hsp60 began to increase at 3 hours in the CA1 cells, and was sustained until 1 day. The mRNAs for 72-kd (hsp70) and 73-kd (hsc70) heat-shock proteins, which are mainly located in the cytoplasm, were induced together in the CA1 cells with a peak at 1 to 2 days. These results suggest that disturbance of a mitochondrial DNA expression occurred in the CA1 neurons at the early stage of reperfusion, and was aggravated in the course of time. The disturbance could cause progressive failure of energy production of the cells, which eventually results in neuronal cell death.

Animals↗
PubMed1995

DNA single-strand breaks in postischemic gerbil brain detected by in situ nick translation procedure.

Using an in situ nick translation procedure, DNA single-strand breaks (SSB) in postischemic gerbil hippocampus were investigated after 15-min forebrain ischemia followed by 0-4h of recirculation. In the control group, increased SSB were noticed in the ependymal cell layer and the dentate gyrus. After 15-min ischemia without recirculation, no remarkable changes in SSB were observed. However, after 1 h of recirculation, a marked increase in SSB was recognized throughout the hippocampus, especially in the cells in CA1 subfield and the dentate gyrus. After 4 h of recirculation, SSB decreased to a level near that of the control group. The results of the present study indicate that ischemic insults may injure intranuclear DNA during postischemic recirculation periods. Although many factors may be involved, activated endonuclease due to an intracellular Ca2+ rise, free radicals, and postischemic hyperthermia appear to be involved in this phenomenon.

Animals↗
PubMed1995

Graded expression of immunomolecules on activated microglia in the hippocampus following ischemia in a rat model of ischemic tolerance.

Preconditioning of the brain with sublethal ischemia protects against neuronal damage following subsequent longer periods of ischemia (ischemic tolerance). In order to evaluate the potential involvement of microglial activation in ischemic tolerance, we immunohistochemically visualized microglial cells in the hippocampus in a rat model of ischemic tolerance. Three minutes of forebrain ischemia (preconditioning ischemia) or sham operation was followed by 6 min of ischemia (second ischemia) 3 days later. The brains were perfusion-fixed after 2 h, 1 day, 3 days, and 7 days. Microglial cells were localized by histochemical staining with isolectin-B4 from Griffonia simplicifolia and by immunohistochemistry of immunomolecules with monoclonal antibodies against major histocompatibility complex class I (OX18) and class II (OX6) antigens and complement receptor type 3 (OX42) and with a rat macrophage marker ED1 and a pan-T cell marker W3/13. Quiescent microglia were stained only by OX42. Preconditioning ischemia led to moderate microglial activation as shown by staining with isolectin, OX42, and OX18. Six minutes of ischemia (without preconditioning) caused early generalized microglial activation as shown by lectin and OX42 after 2 h and by OX18 after 1 day. This length of ischemia produced CA1 neuronal destruction after 3 and 7 days when we observed phagocytic transformation of microglia and increased expression of immunomolecules including OX6 and ED1 However, no staining was seen with W3/13. Following 6-min ischemia with preconditioning, early microglial activation was observed with lectin, OX42, and OX18, but CA1 neuronal damage was prevented and the microglial activation returned toward normal after 7 days. Thus, activation of microglia and expression of immunomolecules occurred in a graded and controlled fashion in response to different degrees of neuronal injury.

Adaptation, Physiological↗
PubMed1995

Expressions of nerve growth factor and p75 low affinity receptor after transient forebrain ischemia in gerbil hippocampal CA1 neurons.

Expressions of nerve growth factor (NGF) and low affinity p75 NGF receptor (p75 NGFR) in gerbil hippocampal neurons after 3.5-min transient forebrain ischemia were studied. Most hippocampal CA1 neurons were lost (neuronal density = 44 +/- 12/mm) at 7 days after recirculation, while no cell death was found in the sham-control neurons (220 +/- 27/mm). NGF immunoreactivity was normally present in the sham-control hippocampal neurons. However, it decreased in hippocampal CA1 neurons, and slightly decreased in the neurons of CA3 and dentate gyrus areas from 3 hr after recirculation. By 7 days, NGF immunoreactivity returned almost completely to the sham-control level in the CA3 and dentate gyrus neurons but decreased markedly in the CA1 neurons. In contrast, p75 NGFR immunoreactivity was scarcely present in the sham-control hippocampal neurons but was induced from 1 hr after recirculation in the CA1 and CA3 neurons and from 3 hr in the dentate gyrus. At 7 days, p75 NGFR immunoreactivity was expressed greatly in the surviving CA1 neurons and the reactive astrocytes but was not seen in the other hippocampal neurons. The markedly decreased NGF and greatly induced p75 NGFR immunoreactivity found in the CA1 neurons after transient forebrain ischemia suggests that NGF and p75 NGFR may be involved in the mechanism of delayed neuronal death.

Animals↗
PubMed1995

Calcium/calmodulin-dependent protein kinase II and protein phosphatase 2B (calcineurin) immunoreactivity in the rat hippocampus long after ischemia.

Calcium/calmodulin-dependent protein kinase II (kinase II) and protein phosphatase 2B (calcineurin) immunoreactivity in the rat hippocampus was studied 100 days after ischemic damage to hippocampal CA1 pyramidal neurons. One-hundred days after ischemia, only a few CA1 pyramidal neurons survived and they exhibited enhanced kinase II and calcineurin immunoreactivity in their basal and apical dendrites. The stratum lucidum of the CA3 (mossy fiber terminal area) had enhanced kinase II and calcineurin immunoreactivity. These results suggest activity-dependent regulation and redistribution of kinase II and calcineurin after intervention in neuronal circuitry.

Animals↗
PubMed1995

Rapid and semiquantitative analysis of HSP72 and HSC73 heat shock mRNAs by mimic RT-PCR.

The amounts of mRNAs for 72 kDa (HSP72) and 73 kDa (HSC73) heat shock proteins were measured semiquantitatively with competitive polymerase chain reaction (PCR) techniques after reverse transcription (RT) using a heterologous DNA fragment (PCR mimic) as an internal standard. The changes of signal intensities of PCR products were well correlated with the amount of mRNA in rat brain measured as optical densities of Northern blot. Thus, an analysis with mimic RT-PCR technique provides a rapid, semiquantitative, and safe method to detect changes of HSP72 and HSC73 mRNAs after brain ischemia.

Animals↗
PubMed1995

Post-ischemic changes of [3H]glycine binding in the gerbil brain after cerebral ischemia.

Sequential changes of [3H]glycine binding in the gerbil were investigated in selectively vulnerable areas 1 h to 7 days after 10 min of cerebral ischemia. A significant reduction in [3H]glycine binding was found in the hippocampus and thalamus from as early as 1 h after ischemia. In contrast, the striatum and frontal cortex showed a significant decline in [3H]glycine binding from 5 h after recirculation. Thereafter, a severe reduction in [3H]glycine binding was observed in all regions 7 days after ischemia. MAP2 (microtubule-associated protein 2) immunoreactivity was unaffected in the hippocampus, frontal cortex and thalamus up to 48 h after ischemia. Thereafter, a severe loss of MAP2-immunoreactive neurons was found in these regions, especially in the hippocampal CA1 sector. However, the striatum showed a severe loss of MAP2 immunoreactivity from 24 h after ischemia. These results demonstrate that transient cerebral ischemia causes severe reduction in [3H]glycine binding throughout the brain, and this reduction precedes the neuronal damage in selectively vulnerable areas. These findings suggest that a neurotransmitter, glycine, may play a key role in the pathogenesis of post-ischemic neurodegeneration in selectively vulnerable areas.

Animals↗