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T Kawamata

Publications and source records attributed to T Kawamata.

At least 127 records · Page 7Linked to original sources
PubMed1995

Age-related decrease of nerve growth factor-like immunoreactivity in the basal forebrain of senescence-accelerated mice.

The senescence-accelerated mouse P10 (SAMP10) is a murine model of accelerated senescence characterized by the deterioration of learning and memory with advancing age. In the present study, we examined the distribution of nerve growth factor (NGF) immunohistochemically in SAMP10 mice and its control strain, SAMR1. In both strains, NGF-like immunoreactivity (NGF-IR) was observed in neurons throughout the entire forebrain and in glial cells in a particular location. In aged SAMP10 mice, each layer of the cerebral cortex retained its NGF-IR, although the thickness of the cortical mantle was markedly decreased in comparison with younger animals. There was an age-related decline in NGF-IR in the substantia innominata of SAMP10 mice at the age of 10 months, when compared to 2-month-old SAMP10. These results indicate age-related decrease of NGF in the basal forebrain in SAMP10 mice.

Age Factors↗
PubMed1995

Monoamine oxidase-B-positive granular structures in the hippocampus of aged senescence-accelerated mouse (SAMP8).

We examined the histochemical localization of monoamine oxidase in the hippocampus of young and old senescence-accelerated mouse (SAM). We found a monoamine oxidase-B-positive granular structure (MGS) in the hippocampus of old SAMP8, an accelerated senescence-prone line of SAM. The MGS was a round-shaped granular structure of 0.5 to 5 microns diameter and usually formed a cluster, the largest diameter of which ranged from 50 to 150 microns. No MGS were found in the hippocampus of young SAMP8 or of young SAMR1, an accelerated senescence resistant line of SAM, and only few, if any, were seen in old SAMR1. A monoamine oxidase-positive astrocyte was usually observed in the central area of each cluster of MGS. Furthermore, the MGS was in close anatomical relationship with monoamine oxidase-positive astrocytic processes. The enzyme inhibition experiments showed that monoamine oxidase activities localized in the MGS and astrocytes were both predominantly of type B. These findings suggest MGS occurs at least partly in monoamine oxidase-B-positive astrocytes. Furthermore, the MGS was similar to a periodic acid-Schiff-positive granular structure, a polyglucosan body previously documented in the brains of old SAMP8 and some other aged mice strains including C57BL/6 and nude mice, in terms of their size, morphological appearances and topographical distribution in the hippocampus. Thus, the present results suggest that monoamine oxidase type B is a proteinaceous component of the periodic acid-Schiff-positive granular structure in aged mice brains, and might provide some clues for clarifying the mechanisms of age-related occurrence of periodic acid-Schiff-positive granular structures in mice brains.

Aging↗
PubMed1995

Management of intracranial hemorrhage associated with anticoagulant therapy.

BACKGROUND: Intracranial hemorrhage may be a particularly devastating complication of anticoagulant therapy. Very few accounts have reported data on the duration of anticoagulant discontinuation following intracranial hemorrhage or the intensity of anticoagulation during treatment for it, although we must adequately manage such a complication. METHODS: We analyzed the management of warfarin-related intracranial hemorrhages in 27 patients with cardiac diseases. We evaluated the degree of anticoagulation using the thrombotest. Anticoagulants were stopped as soon as the diagnosis of intracranial hemorrhage was established by computed tomographic scan. RESULTS: Mechanical valve prosthesis patients, who required intensive long-term anticoagulant therapy, constituted the majority of our series (74.1%). Intraoperative hemostasis was brought under control despite low thrombotest values (13%-68%) at the time of surgery except for the acute subdural hematoma (SDH) patients with cerebral contusion. Early resumption of anticoagulant therapy (within 3 days) did not cause intracranial rebleeding in any operative patient. All the chronic SDH patients and some of the subcortical hematoma patients had a good outcome. All three patients with acute SDH and contusion, however, had a fatal outcome because of intracranial rebleeding within a short period of time or ineffective intraoperative hemostasis. CONCLUSIONS: The patients with anticoagulant-related intracranial hemorrhage may undergo surgery with thrombotest values approximately between 20% and 60%, and anticoagulants can be resumed after an interval of 3 days. Aggressive surgery should particularly be performed in patients with anticoagulation-related chronic SDH or subcortical hemorrhage, as in the cases of anticoagulant-unrelated intracranial hemorrhage.

Adolescent↗
PubMed1995

Inhibition of the high-affinity glutamate uptake system facilitates the massive potassium flux during cerebral ischaemia in vivo.

During cerebral ischaemia, the extracellular concentration of K+ ([K+]e) increases abruptly to 50-60 mM following an initial slow increase to 6-10 mM. We have recently shown that the increase in [K+]e is significantly delayed by in situ administration of kynurenic acid, a broad spectrum antagonist of excitatory amino acids, suggesting that the catastrophic ionic fluxes occurring during ischaemia are initially mediated by EAA-coupled ion channels. In order to confirm further the role of EAAs, the changes in extracellular K+ ([K+]e) and glutamate ([Glu]e) during cerebral ischaemia were determined in the rat hippocampus by microdialysis in vivo, and the effect of dihydrokainate (DHKA), an inhibitor of the high-affinity uptake system of EAAs, was examined by in situ administration through the dialysis probe. DHKA induced a significant increase in baseline [Glu]e and facilitated the abrupt increase in [K+]e during cerebral ischaemia. These findings support the hypothesis that EAAs play a vital role in producing the rapid ionic shifts earlier during cerebral ischaemia.

Animals↗
PubMed1995

Effect of hemidiaphragmatic paresis caused by interscalene brachial plexus block on breathing pattern, chest wall mechanics, and arterial blood gases.

We investigated the effects of hemidiaphragmatic paresis caused by interscalene brachial plexus block on breathing patterns, chest wall mechanics, and arterial blood gas tensions using respiratory inductive plethysmography. Ten healthy patients received interscalene block with 20-40 mL 1.5% lidocaine with epinephrine. Rib cage contribution to tidal volume (%RC) increased from 28.9% +/- 9.7% to 50.0% +/- 8.3% (P < 0.01), respiratory frequency (f) increased from 14.6 +/- 3.2/min to 16.3 +/- 2.4/min (P < 0.05), and PaO2 decreased from 84.7 +/- 7.3 mm Hg to 78.0 +/- 9.5 mm Hg (P < 0.05). No significant changes were observed in tidal volume (VT), minute volume (VE), or PaCO2. These results indicated that VT, VE, and PaCO2 were maintained after interscalene block, apparently by increases in f and %RC to compensate for hemidiaphragmatic paresis caused by interscalene block. Nevertheless, PaO2 was reduced, presumably due to increased ventilation-perfusion mismatching. Recognizing that we studied healthy patients, the decrease in PaO2 may be more in patients with cardiopulmonary disease.

Adult↗
PubMed1995

Role of excitatory amino acid-mediated ionic fluxes in traumatic brain injury.

One major event taking place at the moment of traumatic brain injury in neuronal cells is the occurrence of massive ionic fluxes across the plasma membrane, which can be referred to as traumatic depolarization (TD). Unlike spreading depression, TD can occur over wide brain areas simultaneously. Furthermore, recovery from TD often takes far longer than recovery from ionic perturbation elicited by the passage of a single wave of spreading depression. Neuronal cell damage caused by ischemic brain injury is also initiated by massive ionic fluxes, termed anoxic depolarization. The occurrence of similar ionic events in these two forms of brain injury may account for the genesis of diffuse ischemia-like damage without actual episodes of hypoxia or ischemia in traumatic brain injury. We review the data indicating that excitatory amino acids (EAA) may play a vital role in producing TD, and that such EAA-mediated ionic perturbation is responsible for a number of posttraumatic events including subcellular metabolic dysfunction and cellular responses such as microglial activation and astrocytic transformation. TD may represent one of the most important mechanisms of diffuse neuronal cell dysfunction and damage associated with traumatic brain injury.

Animals↗
PubMed1994

Retention of basic fibroblast growth factor immunoreactivity in dopaminergic neurons of the substantia nigra during normal aging in humans contrasts with loss in Parkinson's disease.

A count of pigmented neurons per mm3 in sections of the substantia nigra at the level where the oculomotor nerve emerges in 11 neurologically normal controls aged 15-82 showed the expected slow loss of such neurons with age. Most (82 +/- 3.8%) of the pigmented neurons showed immunoreactivity for basic fibroblast growth factor (bFGF) and this percentage was unaffected by age. This is in marked contrast to the case in Parkinson's disease where only some 12.7 +/- 2.6% of the remaining dopaminergic neurons showed bFGF-like immunoreactivity, providing further evidence against the hypothesis that Parkinson's disease is due to some early insult followed by age-related attrition of the remaining neurons.

Adolescent↗
PubMed1994

Two types of dystrophic neurites in senile plaques of Alzheimer disease and elderly non-demented cases.

Senile plaques (SPs) occur profusely in brain tissue of Alzheimer disease (AD) cases, and sparsely in brain tissue of elderly normals. Two types of dystrophic neurites (DNs) have been identified in SPs. Type 1 are the classically described elongated forms. Type 2 are globular in shape. Type 1 DNs are stained immunohistochemically by antibodies to A68 protein, other forms of phosphorylated tau, and N-terminal epitopes of amyloid precursor protein (APP), as well as an antibody which preferentially recognized conjugated ubiquitin. Type 2 DNs are stained immunohistochemically by antibodies to chromogranin A and C-terminal epitopes of APP, as well as an antibody which preferentially recognizes free ubiquitin. SPs of AD cases usually contain a mixture of type 1 and type 2 DNs. However, in the neocortex of elderly normals, which have few neurofibrillary tangles and neuropil threads, the DNs in the SPs are restricted to type 2. These data suggest that SPs containing only type 2 DNs may be benign, and independent of neurofibrillary pathology.

Aged↗
PubMed1994

Propentofylline administered by microdialysis attenuates ischemia-induced hippocampal damage but not excitatory amino acid release in gerbils.

Systemic administration of propentofylline (PPF), an adenosine uptake inhibitor, has been demonstrated to protect CA1 pyramidal cells from death following transient cerebral ischemia in gerbils. In order to examine the direct effects of this inhibitor, we tested whether or not PPF administered into the hippocampus in situ through a microdialysis probe could attenuate ischemia-induced excitatory amino acid (EAA) release and prevent subsequent death of CA1 pyramidal cells in the gerbil. The EAA release and death of CA1 pyramidal cells observed in the hippocampus were compared with those in the contralateral hippocampus of the same animal into which vehicle alone was administered. The results indicated that pre- as well as post-treatments with PPF inhibited the death of CA1 pyramidal cells after 5-min ischemia in a dose-dependent manner, but did not significantly alter the EAA release during ischemia and reperfusion in the same animals. While the neuroprotective effect of PPF against ischemic damage has commonly been ascribed to attenuation of EAA release during ischemia, other actions of adenosine such as those influencing the synaptic responses, neuronal excitation, and local cerebral circulation, or as yet unidentified actions may be involved in the observed neuroprotective effects of PPF.

Amino Acids↗
PubMed1994

Expression of chromogranin A in lesions in the central nervous system from patients with neurological diseases.

Expression of chromogranin A in various neurological diseases was examined immunohistochemically using purified anti-human chromogranin A antiserum. The antibody stained dystrophic neurites in senile plaques in Alzheimer disease brain, Pick bodies and ballooned neurons in Pick's disease brain, some Lewy bodies in the substantia nigra of Parkinson's disease, and axonal swellings in various neurological conditions including Parkinson's disease, striatonigral degeneration, Shy-Drager syndrome, amyotrophic lateral sclerosis and cerebral infarction. The present study shows that expression of chromogranin A is not an exclusive feature of Alzheimer disease or Pick's disease, and indicates that it could be a useful marker for various neurological diseases.

Adult↗
PubMed1994

Inhibition of the early phase of free fatty acid liberation during cerebral ischemia by excitatory amino acid antagonist administered by microdialysis.

In order to determine the role of excitatory amino acids (EAAs) in free fatty acid (FFA) liberation during cerebral ischemia, we examined the effect of in situ administration of kynurenic acid, a broad-spectrum antagonist of EAA receptors, by microdialysis on the increase in FFA levels during ischemia in the rat hippocampus. A transient rapid increase in FFA levels, superimposed on a continued slow increase, was observed beginning at 1-2 min after ischemia induction. The early rapid increase in FFAs was profoundly inhibited by kynurenic acid, suggesting that EAAs are critically involved in the early phase of FFA liberation. Development of massive ionic shifts during cerebral ischemia can be delayed for several minutes by kynurenic acid administered by the same procedure, suggesting a vital role for EAAs in the early appearance of anoxic depolarization. The observed inhibition of early FFA liberation may thus be attributable to the delay in development of massive ionic shifts and resultant neurotransmitter release which may activate phospholipase A2 and C.

Amino Acids↗
PubMed1994

Excitatory amino acid release from contused brain tissue into surrounding brain areas.

The EAA release from contused brain tissue and its effect on the extracellular EAA levels in brain areas surrounding the contusion were investigated with microdialysis technique in the rat. A significant increase in extracellular EAA levels was observed in the contused brain tissue. The EAA increase was significantly greater in the contused brain tissue than in the isolated but non-contused brain tissue. It was further demonstrated that EAAs were released from non-contused brain areas 1-2 mm distant from contused brain tissue. No such EAA release from surrounding brain areas was demonstrated when the cavity was filled with isolated but non-contused brain tissue. The increase in EAAs was attenuated by KYN administered through microdialysis, suggesting that the EAA release from the surrounding brain areas appears to be a consequence that is secondary to the EAA release from the contused brain tissue. Such a diffusion-reaction process is probably mediated by the neurotransmitter actions of EAAs. The results of the present study are of clinical importance, since surgical removal of contused brain tissue and administration of EAA antagonists may serve to protect the surrounding brain areas from EAA neurotoxicity.

Animals↗
PubMed1994

Free fatty acid liberation and cellular swelling during cerebral ischemia: the role of excitatory amino acids.

We previously demonstrated the occurrence of cellular swelling during cerebral ischemia in vivo using microdialysis. 14C-Sucrose was pre-perfused into the extracellular space (ECS) as an ECS marker, and cellular swelling was detected as an increase in extracellular concentration of 14C-sucrose. In the present study, we examined in rats the time courses of the increase in FFA in relation to the occurrence of cellular swelling, and the role of excitatory amino acids (EAAs) in these events. A pair of microdialysis probes were placed in the hippocampus bilaterally. One probe was perfused with modified Ringer solution containing kynurenic acid (KYN, 10 mM), a broad-spectrum EAA antagonist, and the other with Ringer solution as a control. At 30 minutes after the initiation of perfusion, ischemia was induced by decapitation. The brain was subjected to microwave irradiation at 0-8 minutes after decapitation, and the FFA levels in the dorsal hippocampus were measured by high performance liquid chromatography. The time course of cellular swelling was determined in a separate group of animals using the previously described method. It was found that arachidonic and stearic acids began to demonstrate a rapid increase during the period from 1 to 2 minutes following ischemia induction. The levels of oleic and palmitic acids demonstrated similar but less marked increase. The rate of increase became less rapid after 4 minutes, suggesting a transient rapid increase superimposed on a background slow increase. The rapid increase roughly corresponded in timing to the occurrence of the early cellular swelling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Cytochrome oxidase and hexokinase activities in an infusion edema model with preserved blood flow.

Despite numerous investigations, the mechanisms underlying the neurological deficits observed in association with interstitial edema remain unclear. A recent study has demonstrated that the cerebral blood flow (CBF) in edematous white matter is unchanged if the blood flow values are corrected for dilution. In contrast, the cerebral glucose metabolism (CMRgl) has been found to be increased. In order to examine the effects of interstitial edema on the oxidative metabolism, we measured the cytochrome oxidase (CYO) activity, a marker of mitochondrial respiration, and the hexokinase (HK) activity, a marker of glycolysis, together with CBF and CMRgl employing the iodoantipyrine and deoxyglucose autoradiography in an infusion edema model in rats. In agreement with the previous study, CBF was not significantly changed in the edematous hemisphere. No significant alterations in CMRgl and HK activity were noted. In contrast, there was a significant decrease in CYO activity in the edematous hemisphere (-17%; p < 0.01), which was correlated to the edema. These findings suggest that interstitial edema causes a decreased mitochondrial respiratory function despite a maintained circulation. This may be explained by postulating a decreased oxygen delivery and/or accumulation of lactate, both of which have been shown to interfere with mitochondrial respiratory function.

Animals↗
PubMed1994

Acetylcholine determination of cerebrospinal fluid in aneurysmal subarachnoid hemorrhage.

Acetylcholine (ACh) concentrations were determined serially in cerebrospinal fluid (CSF) obtained from 23 patients with aneurysmal subarachnoid hemorrhage (SAH) by high-performance liquid chromatography (HPLC) with electrochemical detection (ED). The values of CSF ACh were significantly low in the initial stage of SAH, and increased subsequently but they did not return to control values within 3 weeks. In addition, serial measurements of CSF butyrylcholinesterase (BChE) activity in 12 SAH patients showed that the activity was elevated significantly in the initial stage of SAH and returned to control levels within a week. This discrepancy in the recovery period between the ACh levels and the BChE activity in CSF indicated that significantly lower CSF ACh levels after SAH could not be attributed to plasma BChE contamination of CSF. These results suggested central cholinergic dysfunction after SAH, especially in the initial stage.

Acetylcholine↗
PubMed1994

Inhibitory effects of halothane on high(K+)-induced canine tracheal smooth muscle contraction and intracellular Ca2+ increment.

Halothane is a potent bronchodilator. The effects of halothane on isolated canine tracheal smooth muscle contraction and intracellular Ca(2+) increment induced by a high concentration of K+ were investigated to clarify how this anaesthetic decreases intracellular Ca2+ concentration ([Ca2+]i), an important second messenger. The tension of the muscle strips was measured using an isometric transducer, and [Ca2+]i was measured using a surface fluorescence spectroscopy. Exposure to a 72.7 mM K+ solution increased muscle tension and [Ca2+]i. Halothane (1,2,3 and 4% at the vaporiser) was introduced by bubbling in the presence of the 72.7 mM K+, and significantly decreased both this elevated muscle tension and the [Ca2+]i in a concentration-dependent manner. Similarly, slowly decreasing concentrations of K+ (48.5, 36.4, 24.2 and 18.2 mM) significantly decreased both of these variables. There was no significant difference between the slopes of the two regression lines of changes in muscle tension and changes in [Ca2+]i. From the evidence that tonic increase in [Ca2+]i by high concentrations of K+ is due to the influx of Ca2+ via L-type voltage channels, halothane may modify the L-type channels to decrease Ca2+ influx. In conclusion, halothane inhibits the high K(+)-induced canine airway smooth muscle contraction by decreasing [Ca2+]i. The decrease in [Ca2+]i by halothane might be due to inhibition of voltage-operated channels, especially the L-type channels.

Animals↗