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Biomedical subjects

K Kogure

Publications and source records attributed to K Kogure.

At least 307 records · Page 17Linked to original sources

Regional impairment of protein synthesis following brief cerebral ischemia in the gerbil.

Regional cerebral protein synthesis following brief ischemia was investigated in the Mongolian gerbil, utilizing L-[methyl-14C]methionine autoradiography. Transient ischemia was induced for 1, 2 or 3 min. At various recirculation periods up to 48 h, animals received a single dose of L-[methyl-14C]methionine and then were terminated 35 min later. Sham-operated animals showed a normal pattern of amino acid incorporation into the proteins of the brain. Following 1-min ischemia, the pattern of protein synthesis was similar to that in the sham-operated gerbils. Ischemia for 2 min, however, caused marked inhibition of protein synthesis in the neocortex, striatum, hippocampal CA1 sector and the thalamus at 1 h of recirculation. Extensive recovery of protein synthesis was found in the neocortex, the striatum, the hippocampal CA1 sector and the thalamus at 5-24 h of recirculation, but, a slight inhibition was detectable in the hippocampal CA1 sector in one of six animals. This inhibition had fully recovered at 48 h of recirculation. Following 3-min ischemia, severe impairment of protein synthesis was found in the neocortex, striatum, the whole hippocampus and the thalamus. After 5-24 h of recirculation, the protein synthesis in these regions had gradually recovered, except that complete lack of amino acid incorporation was seen in the hippocampal CA1 subfield. This impairment of protein synthesis in the hippocampal CA1 sector was not recovered at 48 h of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cyclosporin A-induced tolerance is not amplified by the addition of a steroid therapy.

The effect of adding steroids to a cyclosporin A (CyA) schedule designed to induce tolerance to heart allografts in rats was investigated. CyA treatment alone, at a dose of 15 mg/kg per day for 2 weeks, resulted in the successful induction of tolerance (graft survival greater than 100 days) in 70% of the rats. The inclusion of 5 mg/kg of steroids (Solumedrone), administered IM for 40 or 60 days, not only failed to improve this long-term survival (LTS) rate achieved with CyA alone but reduced it from 70% to 50% after 40 days of steroid treatment and to 30% after 60 days of steroid treatment. The administration of 5 mg/kg and 40 mg/kg of steroids during the "high-risk" period for graft rejection (days 30-50 or 40-60) was shown to delay but not prevent subsequent rejections from occurring. Steroid treatment alone (5 mg/kg per day) was found to be ony weakly immunosuppressive. Thus, we have demonstrated that the addition of steroids to a CyA tolerizing schedule was detrimental to the induction of tolerance.

Animals↗

Neuronal damage and calcium accumulation following transient cerebral ischemia in the rat.

The purpose of this study was to examine the distribution of neuronal damage following transient cerebral ischemia in the rat model of four-vessel occlusion utilizing light microscopy as well as 45Ca-autoradiography. Transient ischemia was induced for 30 min. The animals were allowed to survive for 7 d after ischemia. In the animals subjected to ischemia, the most frequently and seriously damaged areas were the paramedian region of hippocampus, the hippocampal CA1 sector, and the dorsolateral part of striatum, followed by the inferior colliculus, the substantia nigra, the frontal cortex, and the thalamus, which were moderate damaged. Furthermore, the cerebellar Purkinje neurons, the hippocampal CA4 sector, the medial geniculate body, and the hippocampal CA3 sector were slightly affected. 45Ca-autoradiographyic study also revealed calcium accumulation in the identical sites of ischemic neuronal damage, except for the frontal cortex. Regional cerebral blood flow during 10 min of ischemia was severely decreased in selectively vulnerable areas. The blood flow in the medial geniculate body, the substantia nigra, the inferior colliculus, and the cerebellum was less pronounced than that in the selectively vulnerable areas. The present study demonstrates that transient cerebral ischemia can produce significant neuronal damage not only in the selectively vulnerable regions, but also in the brainstem.

Animals↗

Comparative neuroprotective effects of pentobarbital, vinpocetine, flunarizine and ifenprodil on ischemic neuronal damage in the gerbil hippocampus.

We studied the protective effects of pentobarbital, vinpocetine, flunarizine, and ifenprodil on delayed neuronal death using Mongolian gerbils. The animals were allowed to survive for 7 days after 5 min of cerebral ischemia induced by bilateral occlusion of the common carotid arteries. Hippocampal cell loss was quantified histologically 7 days following ischemia. Intraperitoneal application of pentobarbital (40 mg/kg) 30 min and vinpocetine (50 and 100 mg/kg) 10 min before ischemia significantly reduced neuronal cell loss in the CA1 sector. However, the intraperitoneal administration of flunarizine (10 and 30 mg/kg) and ifenprodil (10 and 30 mg/kg) 15 min before ischemia was not protective. The results suggest that pentobarbital and vinpocetine prevent ischemic neuronal damage, but not flunarizine and ifenprodil. These findings are of interest in relation to the mechanism of delayed neuronal death.

Animals↗

Ischemia-induced slowly progressive neuronal damage in the rat brain.

Ischemic neuronal damage has been believed to make rapid progress in the course of a few days even in delayed selective neuronal death, to say nothing of acute brain necrosis. In the present study, however, we demonstrate for the first time a new type of ischemia-induced neuronal damage which progresses in the course of several weeks or a few months and we tentatively call this process "slowly progressive neuronal damage". We have focused on the chronological changes of neuronal damage in the dorsolateral striatum and neocortex following various durations of transient middle cerebral artery occlusion, which does not cause cerebral infarction and is clinically designated "transient ischemic attack". In the rats subjected to 15 min middle cerebral artery occlusion, the neocortex and lateral striatum were rarely damaged, whereas the small to medium-sized neurons only in the narrow area restricted to the dorsal striatum showed slowly progressive neuronal damage. Prolongation of ischemic duration to 30 min accelerated the evolution of neuronal damage in the dorsolateral striatum and also extended the distribution of neuronal damage to the neocortex, especially to layer III and more superficial layers. Further prolongation of ischemic duration to 45 min resulted in more rapid progress of selective neuronal death in those areas described above, whereas no animal escaped 60 min ischemia, without acute total tissue necrosis in the middle cerebral artery territory. Ischemia-induced slowly progressive neuronal damage may be implicated in the pathogenesis of such slowly progressive neurologic deterioration as dementia or Parkinsonism in patients with cerebral arteriosclerosis.

Animals↗

Post-ischemic synaptic plasticity in the rat hippocampus after long-term survival: histochemical and autoradiographic study.

The hippocampus provides a suitable area in the brain for the analysis of neuronal plasticity after application of a selective lesioning technique. Using histochemistry and autoradiography, we studied synaptic reorganization in the rat hippocampus with selective CA1 pyramidal cell lesioning caused by transient forebrain ischemia after long-term survival. An autoradiographic study was performed on second messenger systems ([3H]inositol 1,4,5-trisphosphate, [3H]forskolin and [3H]phorbol 12,13-dibutyrate binding). One-hundred days after ischemia, depletion of CA1 pyramidal cells and marked shrinkage of the CA1 subfield was noted in spite of unaltered thickness of the CA3 band and of the dentate molecular layers. Although neuronal density in the CA3 region of animals killed seven days after ischemia was not different from the normal group, 78% of animals showed neuronal loss of 30-50% in the stratum pyramidale of the CA3b 100 days after recirculation. Sixty-seven per cent of animals exhibited supragranular mossy fiber sprouting in the dentate gyrus. However, CA3 neuronal loss did not correlate with mossy fiber sprouting. Succinic dehydrogenase was depleted in the CA1 100 days after ischemia, and animals with CA3 damage showed a reduction of succinic dehydrogenase activity in the CA3. In contrast to the unaltered acetylcholinesterase in the animals killed seven days after ischemia, high density bands of acetylcholinesterase activity in the stratum pyramidale of the CA1 were found to be broadened 100 days after ischemia. In the CA1 subfield, subnormal activity of [3H]phorbol 12,13-dibutyrate and [3H]forskolin binding were observed in spite of the depleted [3H]inositol 1,4,5-triphosphate binding. [3H]Forskolin binding in the hilus had increased by 62% 100 days after ischemia, although binding in the stratum lucidum of the CA3 and in the stratum moleculare of the dentate gyrus was unaltered. However, no visible supragranular increase in [3H]forskolin binding was observed. These results indicate that long-term survival after CA1 pyramidal cell depletion caused by transient forebrain ischemia induced the modulation of neuronal activity and synaptic rearrangements in the whole hippocampal formation.

Acetylcholinesterase↗

Regional neuroprotective effects of pentobarbital on ischemia-induced brain damage.

We investigated the neuroprotective effect of pentobarbital, a GABAA receptor-effector, on ischemic neuronal damage in the gerbils. The animals were allowed to survive for 7 days after 10-min ischemia induced by bilateral occlusion of the common carotid arteries. Morphological changes and abnormal calcium accumulation were evaluated in selectively vulnerable areas after ischemia. Pentobarbital (40 mg/kg, IP), administered 30 min prior to ischemia, significantly reduced neuronal cell loss in the neocortex, the striatum, and the hippocampal CA3 sector. However, pentobarbital failed to prevent the damage to the hippocampal CA1 sector and the thalamus. 45Ca autoradiographic study also revealed that a marked calcium accumulation was found in the selectively vulnerable regions after ischemia, which was consistent with the extent of histological neuronal damage. The abnormal calcium accumulation was reduced in the sites corresponding to most of the regions in which the protective effect of pentobarbital was found. The results suggest that ischemia-induced neuronal damage may be partly caused by an imbalance between excitatory and inhibitory input.

Animals↗

Auditory sound agnosia without aphasia following a right temporal lobe lesion.

A 55-year-old right-handed man showed inability to recognize the meaning of non-verbal sounds without impairment of language comprehension after a cerebrovascular accident. His auditory acuity was intact and no other sign of agnosia, apraxia or aphasia was detectable. His errors on a test of sound recognition were acoustic rather than semantic. Brain CT scan showed a small lesion in the posterior part of the right temporal lobe. This case suggests that auditory sound agnosia without language disorder can ensure a lesion confined to the right hemisphere, and that the deficit is discriminative rather than associative in nature.

Agnosia↗

Staurosporine, a novel protein kinase C inhibitor, prevents postischemic neuronal damage in the gerbil and rat.

The protective effects of protein kinase inhibitors and a calmodulin kinase inhibitor (W-7) against ischemic neuronal damage were examined in the CA1 subfield of the hippocampus. Staurosporine, KT5720, and KT5822 were used as inhibitors of protein kinase C (PKC), cyclic AMP-dependent protein kinase, and cyclic GMP-dependent protein kinase, respectively. All test compounds were injected topically into the CA1 subfield of the hippocampus. In the gerbil ischemia model, staurosporine (0.1-10 ng) administered 30 min before ischemia prevented neuronal damage in a dose-dependent manner. However, KT5720, KT5822, and W-7 were ineffective, even at a dose of 10 ng. In the rat ischemia model, staurosporine (10 ng) also prevented neuronal damage when administered before ischemic insult, although staurosporine administered 10 or 180 min after recirculation was ineffective. These results suggest the involvement of PKC in CA1 pyramidal cell death after ischemia and that the fate of vulnerable CA1 pyramidal cells through PKC-mediated processes could be determined during the early recirculation period.

Alkaloids↗

Brain damage in a new hemorrhagic shock model in the rat using long-term recovery.

A new shock model in the rat using hemorrhagic hypotension for production of brain damage is described. Hemorrhagic shock was induced by lowering arterial blood pressure with bleeding. The MABP was maintained at approximately 25 mm Hg, accompanied by isoelectric EEG, and then shed blood was retransfused. At 1 week of recovery, morphological and 45Ca autoradiographic changes were examined. No brain damage was observed in rats after 1 min of isoelectric EEG. Mild neuronal damage in the hippocampal CA1 subfield was seen in some animals after 2 min of isoelectric EEG. Severe and consistent neuronal loss in the hippocampal CA1 subfield was recognized after 3 min of isoelectric EEG. Additional damage was also seen in the dentate hilus and the thalamus in some animals. This model can be used to study the pathophysiology of postshock brain damage and to assess new therapies following shock.

Animals↗

Ischemia-induced alterations in lipid metabolism of the gerbil cerebral cortex: I. Changes in free fatty acid liberation.

Does the impaired lipid metabolism during non-lethal transient ischemia truly recover within a few hours after recirculation? In an attempt to answer this question, we first investigated the time course of the changes in the amount and composition of free fatty acids (FFAs) accumulated during 5-min ischemia and after various postischemic recirculation durations (3 min, 1 h, 24 h, 3 days, and 6 days) in the gerbil cerebral cortex. Then those of FFAs liberated in response to the second 5-min ischemia at various recirculation intervals (3 min, 1 h, 3 days, and 6 days) following the initial one were also measured to evaluate the changes in the cellular response. The former study disclosed that the FFA levels transiently returned to the control levels at 1-h recirculation, increased again a few days after the onset of recirculation, followed by the final return to the control levels after 6-day recirculation. The latter study disclosed that the cellular response to the second ischemia was quite different from that to the initial one even after 6-day recirculation, suggesting that membrane lipid metabolism had not yet been recovered even at such a late period. We discuss the significance of the alterations in lipid metabolism.

Animals↗

Vinconate prevents ischemic neuronal damage in the rat hippocampus.

The neuroprotective effect of vinconate, a novel vinca alkaloid derivative, was examined in a rat model of forebrain ischemia induced by 4-vessel occlusion. Hippocampal cell loss was quantified histologically 3 days after 10 or 15 min of ischemia. Intraperitoneal application of vinconate (25 and 50 mg/kg) 10 min before and immediately after 10 min of ischemia significantly reduced the neuronal cell loss in the CA1 sector of the hippocampus. Protective effect of vinconate against 15 min of ischemia was reduced, but there was still significant protection at the higher dose. Autoradiography using 14C-vinconate showed that the drug easily penetrates the blood-brain barrier and distributes in the hippocampus. The result suggests that vinconate prevents ischemic neuronal damage by direct action on the hippocampal CA1 neurons.

Animals↗

White matter lucencies in multi-infarct dementia: a somatosensory evoked potentials and CT study.

White matter low attenuation (WMLA) on computed tomography (CT) and the central conduction time (CCT) measured by median nerve-somatosensory evoked potentials were examined in 12 multi-infarct dementia (MID) patients, 10 patients with multiple infarcts (MI) without dementia and 11 age-matched controls. Patients with deep vascular lesions without cortical infarcts on CT were included. In MID, prolongation of CCT and moderate to severe WMLA were observed. The CCT and WMLA in MI patients were intermediate. The CCT was longer when the WMLA was more extensive. The result suggests that white matter disease in MID is concerned to the occurrence of dementia by disturbing axonal conduction.

Aged↗

Identification of deep-sea-sediment bacteria which produce tetrodotoxin.

Forty-nine bacterial strains were isolated from deep-sea sediments. Among them, 22 strains were shown by the tissue culture assay method to produce sodium channel blockers. For some strains, high-performance liquid chromatography analysis confirmed that the blocker was tetrodotoxin. Tetrodotoxin-producing bacteria seem to be widespread in marine sediment.

Journal Article↗

Calcium antagonist, adenosine A1, and muscarinic bindings in rat hippocampus after transient ischemia.

The protective roles of Ca2+ channel blockers against ischemic hippocampal damage are still debated. We used autoradiography to study postischemic L-type Ca2+ channels (1,4-dihydropyridine Ca2+ channel blocker binding), adenosine A1 receptors, and muscarinic cholinergic receptors in the rat hippocampus using [3H]PN200-110 (PN), [3H]cyclohexyladenosine (CHA), and [3H]quinuclidinyl benzilate (QNB), respectively, in 49 rats subjected to 20 minutes of forebrain ischemia. The rats were decapitated after 1 (n = 7), 3 (n = 7), 6 (n = 8), 12 (n = 7), 24 (n = 6), 48 (n = 6), or 168 (n = 8) hours of recirculation; eight control rats were sham-operated but experienced no cerebral ischemia. Reduced receptor binding preceding the delayed death of CA1 pyramidal cells was first observed in the stratum oriens of the CA1 subfield. Significant reductions in [3H]PN, [3H]CHA, and [3H]QNB bindings of this stratum compared with control were noticed after 3 (35%, p less than 0.01), 12 (31%, p less than 0.01), and 1 (10%, p less than 0.05) hours of recirculation, respectively. By 168 hours after ischemia (when the populations of CA1 pyramidal cells were depleted) all strata in the CA1 subfield had lost most of their receptor sites, and [3H]PN, [3H]CHA, and [3H]QNB bindings in the stratum oriens were decreased to 23%, 30%, and 63% of control (p less than 0.01). Although [3H]PN binding in the CA3 subfield did not change significantly during 168 hours after ischemia, the histologically intact dentate gyrus exhibited a 31% loss of binding sites compared with control (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Sequential cerebral blood flow changes in short-term cerebral ischemia in gerbils.

Using quantitative autoradiography, we studied sequential changes in regional cerebral blood flow during and after 2 minutes of bilateral common carotid artery occlusions in 18 gerbils. Occlusion (n = 4) led to severe ischemia in the forebrain (regional cerebral blood flow less than 5% of control [n = 4]) and midbrain (regional cerebral blood flow less than 10% of control), but was morphologically nonlethal. Reperfusion of the brain was complete, and regional cerebral blood flow was not different from control 1 minute after ischemia (n = 4), but hypoperfusion (regional cerebral blood flow 30-50% of control) occurred at 5 minutes (n = 3) and was pronounced at 1 hour (n = 4); at this stage blood flow was inhomogeneous. Hypoperfusion had disappeared at 4 hours (n = 3). Our results indicate that the well-documented sequence of cerebral blood flow changes (i.e., ischemia, initial recovery of blood flow, and delayed hypoperfusion) takes place even after nonlethal cerebral ischemia.

Animals↗

Effect of nimodipine on ischemia-induced brain edema and mortality in a novel transient middle cerebral artery occlusion model.

A novel transient middle cerebral artery (MCA) occlusion model in the rat was used to evaluate the effect of nimodipine on brain edema and mortality. Nimodipine (30 micrograms/kg) administered immediately after 3 hr of transient unilateral MCA occlusion attenuated significantly the post-ischemic increase of tissue water content and partly attenuated 45Ca accumulation in the parieto-temporal cortex ipsilateral to the left MCA occlusion 3 hr after reperfusion. Nimodipine decreased the mortality rate at 6 and 9 hr after recirculation, although the survival rate at 24 hr after recirculation was not different from the control group. These results suggest that nimodipine has beneficial effects in the early phase of the reperfusion period.

Animals↗

Effects of hand and spatial conditions on visual line bisection.

This study examined the effects of hand and spatial conditions on a visual line bisection task with normal right-handers and proposed a normal range of deviation for this task in middle and advanced age. Twenty-four normal dextrals in their fifties and sixties performed a visual line bisection task using either the left or right hand under three spatial conditions: at the midline and in the left and right hemispaces. Our results revealed that performance was significantly affected by the hand used but not spatial conditions: Left hand performance was significantly further leftward than right hand performance. There was no significant interaction between the hand and spatial conditions. The mean deviation of the right hand was 2.2% of the half line length to the right of the true center. The possibility of left unilateral spatial neglect should be considered if a patient bisects a line with a deviation greater than 10% of the half line length to the right.

Aged↗