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Tatsuru Arai

Publications and source records attributed to Tatsuru Arai.

At least 19 recordsLinked to original sources
PubMed2006

Suppression of inflammatory cell recruitment by histamine receptor stimulation in ischemic rat brains.

Inflammation is a crucial factor in the development of ischemia-induced brain injury. Since facilitation of central histaminergic activity ameliorates reperfusion injury, effects of postischemic administration of L-histidine, a precursor of histamine, and thioperamide, a histamine H3 receptor antagonist, on inflammatory cell infiltration were evaluated in a rat model of transient occlusion of the middle cerebral artery. After reperfusion for 12, 24, or 72 h following 2 h of occlusion, brain slices were immunohistochemically stained with antibodies against myeloperoxidase and CD68, which were markers of polymorphonuclear leukocytes and macrophages/microglia, respectively. After reperfusion for 12-24 h, the number of neutrophils on the ischemic side increased markedly, whereas the increase was not observed on the contralateral side. Administration of L-histidine (1000 mg/kg x 2, i.p.), immediately and 6 h after reperfusion, reduced the number of neutrophils to 52%. Simultaneous administration of thioperamide (5 mg/kg, s.c.) further decreased the number of neutrophils to 32%. Likewise, the ischemia induced increase in the number of CD68-positive cells after 24 h was suppressed by L-histidine injections. The L-histidine administration decreased the number of CD4+ T lymphocytes on both ischemic and contralateral sides after 12 h, and concurrent administration of thioperamide prolonged the effect. Although administration of mepyramine (3 nmol, i.c.v.) did not affect suppression of leukocyte infiltration, ranitidine tended to reverse the effect of L-histidine. These data suggest that enhancement of central histaminergic activity suppresses inflammatory cell recruitment after ischemic events through histamine H2 receptors, which may be a mechanism underlying the protective effect of L-histidine.

Animals↗
PubMed2006

A comparison of protective effects between L-histidine and hypothermia against ischemia-induced neuronal damage in gerbil hippocampus.

An increase in the histamine concentration in the brain has been demonstrated to provide protective effects against ischemia/reperfusion brain injury. Since hypothermia and barbiturates are also regarded to protect ischemic brains, effects of postischemic treatments were compared in gerbils between mild hypothermia and intraperitoneal administration of L-histidine, a precursor of histamine. Furthermore, effects of thioperamide, a histamine H(3) receptor antagonist, were evaluated in histidine-treated gerbils after 60 days. Transient forebrain ischemia for 4 min at 37 degrees C provoked severe neuronal damage in the hippocampal CA1 pyramidal cells after 7 days. Postischemic hypothermia (33 degrees C) for 3 h under pentobarbital anesthesia alleviated neuronal death, and the number of preserved neurons was 77+/-56/mm (mean+/-S.D., n=14). The effect of L-histidine injected three times, immediately, 6 h, and 24 h after reperfusion (1,000 mg/kg, i.p., each), was more prominent than that of hypothermia, and the number of preserved neurons was 142+/-55/mm (n=14). When the histologic outcome was evaluated after 60 days, most neurons were damaged in both the hypothermic and histidine groups. The improvement of the histologic outcome was observed even after 60 days in animals injected with thioperamide, immediately and 6 h after reperfusion (5 mg/kg, s.c., each), with three injections of l-histidine. The number of preserved neurons was 133+/-88/mm (n=10), while that in the hypothermic group was 7+/-15 (n=10). Activation of the central histaminergic system provides beneficial effects against cerebral ischemia.

Animals↗
PubMed2006

Suppression of ischemia/reperfusion liver injury by histamine H4 receptor stimulation in rats.

Inflammatory reactions play an important role in ischemia/reperfusion injury in various organs. Since histamine is closely related to inflammatory reactions and immune responses, effects of postischemic administration of histaminergic ligands on ischemia-induced liver injury were examined in rats. Animals were subjected to warm ischemia for 30 min by occlusion of the left portal vein and hepatic artery under halothane anesthesia, and liver damage was evaluated by assessing plasma concentrations of transaminases after 24 h. Warm ischemia for 30 min provoked severe liver damage after 24 h, and the plasma concentrations of alanine transaminase (ALT) and aspartate transaminase (AST) were 8600 I.U./l and 13100 I.U./l, respectively. Subcutaneous injections of histamine twice, immediately and 6 h after reperfusion (20 mg/kg, each), alleviated liver damage. The plasma concentrations of ALT and AST in the histamine group were 35% and 24% of those in the control group, respectively. Neither mepyramine (3 mg/kg x 2), an H1 antagonist, nor cimetidine (15 mg/kg x 2), an H2 antagonist, affected the outcome in histamine-treated rats. However, thioperamide (5 mg/kg x 2), an H3/H4 antagonist, completely abolished the alleviation caused by histamine. Administration of dimaprit (1-10 mg/kg x 2), an H2/H4 agonist, mimicked the protective effect of histamine, and the effect of dimaprit is reversed by thioperamide, whereas neither H1 nor H2 antagonists altered the outcome caused by dimaprit. Clozapine (15 mg/kg x 2), an H4 agonist, also mimicked the protective effect of histamine. These findings indicate that stimulation of histamine H4 receptors after ischemic events prevents development of reperfusion injury in the liver.

Alanine Transaminase↗
PubMed2005

Reduction in brain infarction by augmentation of central histaminergic activity in rats.

Inflammation is a factor in the aggravation of reperfusion injury after cerebral ischemia. Since histamine H(2) receptor stimulation suppresses inflammatory reactions, effects of the central histaminergic activation on brain infarction were examined in rats. Focal cerebral ischemia for 2 h was provoked by transient occlusion of the right middle cerebral artery, and the infarct size was determined by 2,3,5-triphenyltetrazolium chloride stain after 24 h. Effects of postischemic administration of thioperamide, an H(3) antagonist, and metoprine, an inhibitor of histamine-N-methyltransferase, were evaluated in rats treated with l-histidine, a precursor of histamine. Furthermore, effects of these agents on changes in the striatal histamine level were examined by a microdialysis procedure. Focal ischemia provoked marked damage in rats treated with l-histidine (1000 mg/kg) alone. Administration of l-histidine (1000 mg/kg) with either thioperamide (5 mg/kg) or metoprine (10 mg/kg) alleviated brain infarction. The size of brain infarction was 27% and 10% of that in animals treated solely with l-histidine, respectively. The combination treatment with thioperamide and metoprine decreased the size of brain infarction in rats given l-histidine (500 mg/kg), although protective effects were not clear without l-histidine. A marked increase in the histamine concentration was observed in the histidine plus metoprine group, the value being 363% of that in the saline-injected group after 2-3 h. The histamine concentrations in the histidine group and histidine plus thioperamide group were 188% and 248%, respectively. These findings indicate that facilitation of central histaminergic activity reduced the brain infarction.

Animals↗
PubMed2005

Prevention of brain infarction by postischemic administration of histidine in rats.

Focal cerebral ischemia for 2 h by occlusion of the right middle cerebral artery provoked severe brain infarction in the rat brain after 24 h. Intraperitoneal administration of histidine, a precursor of histamine, immediately and 6 h after reperfusion, alleviated brain infarction. The infarct size in the histidine (200 mg/kg, 500 mg/kg, and 1000 mg/kg, each time) groups was 71%, 39%, and 7% of that in the control group, respectively. Although intracerebroventricular administration of mepyramine (3 nmol), an H1 antagonist, did not affect the morphologic outcome in histidine-treated rats, ranitidine (30 nmol), an H2 antagonist, completely abolished the alleviation caused by histidine. These findings indicate that postischemic administration of histidine prevents development of brain infarction by stimulating central histamine H2 receptors.

Animals↗
PubMed2005

Facilitation of serotonergic activity and amnesia in rats caused by intravenous anesthetics.

BACKGROUND: Midazolam and propofol often provoke retrograde amnesia after recovery from anesthesia in humans. Because an increase in central serotonergic activity impairs learning and memory, the authors examined the relation between changes in the serotonergic activity caused by intravenous anesthetics and memory. METHODS: Changes in extracellular concentrations of monoamines and their metabolites were investigated in rat striatum by a microdialysis procedure, and the effects of intraperitoneal injections of midazolam (5 mg/kg), propofol (60 mg/kg), and pentobarbital (15 mg/kg) were then examined. To evaluate the behavioral alteration with these agents, the authors used a step-through passive avoidance test. RESULTS: Midazolam and propofol slightly increased the extracellular concentration of 5-hydroxytryptamine in the striatum, although pentobarbital did not produce any changes. Midazolam and propofol increased the extracellular concentration of 5-hydroxyindoleacetic acid, a metabolite of 5-hydroxytryptamine, with the peak values each 138% and 138% of that in saline-injected animals, respectively. However, pentobarbital decreased the 5-hydroxyindoleacetic acid concentration to 61% of that in the saline group. Administration of midazolam or propofol immediately after the completing the passive avoidance learning reduced step-through latencies after 24 h, although pentobarbital-injected animals maintained a consistent performance. The effects of midazolam and propofol on step-through latencies were completely antagonized by intracerebroventricular administration of spiroxatrine (5 microg), a 5-hydroxytryptamine 1A antagonist, 30 min before training. CONCLUSIONS: Midazolam and propofol increased central serotonergic activity and provoked retrograde amnesia. Because amnesia was completely diminished by a 5-hydroxytryptamine antagonist, facilitation of the serotonergic system may be involved in retrograde amnesia caused by these agents.

Amnesia↗
PubMed2005

Flumazenil-induced improvement of the central dopaminergic system in rats with acute hepatic failure.

Several reports have demonstrated the alleviation of hepatic encephalopathy by flumazenil, an antagonist of benzodiazepine receptors. As changes in central monoaminergic activity are involved in the mechanisms for hepatic encephalopathy, the effects of flumazenil on central monoaminergic activity were evaluated in acute hepatic failure produced by ischemia-reperfusion injury in rats. Eighteen male Wistar rats were evenly assigned to three groups: sham-operated group given saline, liver-ischemic group given saline, and liver-ischemic group given flumazenil. Flumazenil (1 mg/kg) or saline (10 mL/kg) was intraperitoneally administered three times, at 1, 6, and 24 hours after 90 minutes of liver ischemia produced by occlusion of the left portal vein. The extracellular concentrations of neurotransmitter amino acids, monoamines, and their metabolites were determined in the striatum using a microdialysis procedure. Another set of 12 rats was subjected to liver ischemia, and the effect of flumazenil on spontaneous motor activity was examined after 24 hours. The extracellular concentration of 3,4-dihydroxyphenylacetic acid, a metabolite of dopamine, decreased to 39% of that in sham-operated animals 24 hours after surgery (P < 0.05), although the dopamine level did not change. The treatment with flumazenil completely abolished the decrease in the metabolite (P < 0.05). Although the glutamate level in the injured animals decreased to 42% of that in sham-operated animals (P < 0.05), no remarkable increase in the glutamate level was observed in animals treated with flumazenil. Spontaneous motor activity decreased 24 hours after surgery in animals subjected to liver ischemia. Flumazenil led to improvement of spontaneous motor activity 5 minutes after administration, but this effect was not observed after 30 minutes. The restoration of the central dopaminergic function may be a contributing factor in the improvement of hepatic encephalopathy.

Ammonia↗
PubMed2005

Suppression of energy requirement by lidocaine in the ischemic mouse brain.

Effects of lidocaine on parameters of membrane functional integrity were investigated in the mouse brain. Changes in the direct-current potential shift in the cerebral cortex provoked by decapitation ischemia were compared in animals given lidocaine (0.05, 0.25, or 1.0 micromol, intracerebroventricular) or saline 15 minutes before ischemia. The brain content of adenosine 5'-triphosphate (ATP) was measured in animals subjected to 0, 0.5, 1, and 2 minutes of decapitation ischemia, and the effect of preischemic administration of lidocaine (0.25 micromol, intracerebroventricular) was evaluated. Na+, K+-ATPase, and Ca2+-ATPase activity was evaluated in brains pretreated with lidocaine (0.25 micromol, intracerebroventricular) or saline 15 minutes before decapitation. Changes in the intracellular Ca concentration ([Ca2+]i) were evaluated in hippocampal slices and the effects of lidocaine (50, 100, or 400 microM) were assessed in the hippocampal CA1 field and dentate gyrus at pH 7.4 and pH 6.8 every 60s for a duration of 50 min. The preischemic administration of lidocaine (1.0 and 0.25 micromol) delayed the onset of anoxic depolarization to 49 seconds and 44 seconds, respectively, as compared with that in the saline group at 27 seconds. Lidocaine maintained ATP levels higher than those in corresponding saline groups, values being 165% after 1 minute of ischemia and 212% after 2 minutes, respectively. Lidocaine did not affect Na+, K+-ATPase, and Ca2+-ATPase activity. Lidocaine did not affect changes in the [Ca2+]i in either area at either pH. The findings may suggest that lidocaine maintains the energy level by delaying depolarization in neurons, which may contribute to removal of cytosolic Ca2+ in ischemic states.

Acidosis↗
PubMed2005

Acute effects of 17beta-estradiol on oxidative stress in ischemic rat striatum.

Changes in the extracellular concentrations of monoamines, their metabolites, and hydrogen peroxide in the rat striatum during middle cerebral artery (MCA) occlusion and reperfusion were investigated by a microdialysis procedure, and the effects of 17beta-estradiol and tamoxifen (an antagonist of estrogen receptors) on them were evaluated. Male Wistar rats were randomly divided into four groups: saline-treated animals, 17beta-estradiol-treated animals, saline-plus-tamoxifen-treated animals, and 17beta-estradiol-plus-tamoxifen-treated animals. Sixty minutes after an intracerebroventricular injection of saline (20 microL) or 17beta-estradiol (150 microg/20 microL), all animals were subjected to 15-minute MCA occlusion under anesthesia. Tamoxifen (1.5 mg) or vehicle was intravenously administered 30 minutes before the saline or 17beta-estradiol treatment. Microdialysis samples in the striatum were collected every 15 minutes, and concentrations of monoamines, their metabolites, and hydrogen peroxide were determined. Delayed neuronal death in the striatal neurons was observed after 7 days by light microscopy. Administration of 17beta-estradiol reduced neuronal damage caused by focal ischemia. Tamoxifen did not affect the improvement by 17beta-estradiol. Although transient ischemia produced a marked increase in the dopamine level, there were no differences in the peak level among the groups. The level of hydrogen peroxide was increased after reperfusion in the saline group. The level in the 17beta-estradiol group was suppressed before induction of ischemia, and no increase was observed by ischemia. Tamoxifen did not affect the suppression of the increase by 17beta-estradiol. Acute treatment with 17beta-estradiol showed a protective effect against ischemia-reperfusion injury. Antioxidant effects of the agent may be a predominant mechanism underlying the protection.

Animals↗
PubMed2004

Alleviation of ischemic neuronal damage by postischemic loading with histidine in the rat striatum.

Inflammatory reactions play an important role in ischemia-reperfusion injury in the brain. Since histamine H(2) action suppresses inflammatory reactions, effects of postischemic loading with histidine, a precursor of histamine, were examined. Focal cerebral ischemia for 15 min was provoked by transient occlusion of the right middle cerebral artery in rats, and delayed neuronal death were evaluated in striatal neurons after 7 days. Histidine was administered four times, immediately, 6, 24, and 48 h after reperfusion of blood flow (1000 mg/kg, i.p., each time). To examine the role of histaminergic action on changes in histologic outcome, effects of mepyramine (3 nmol, i.c.v.), an H(1) antagonist, and ranitidine (30 nmol, i.c.v.), an H(2) antagonist, were evaluated in histidine-treated rats. Transient ischemia for 15 min provoked severe neuronal damage in the saline-injected control group, and the number of striatal neurons decreased to 21% of that on the contralateral side. Administration of histidine alleviated ischemic neuronal damage, and the number of preserved neurons was 76% of that on the contralateral side. Simultaneous administration of mepyramine with histidine did not affect the histologic outcome. However, administration of ranitidine abolished the alleviation by histidine. These findings indicate that the elevation of histamine H(2) receptor stimulation by massive administration of histidine suppresses reperfusion injury in the brain.

Animals↗
PubMed2004

Alleviation of ischemic neuronal damage by histamine H2 receptor stimulation in the rat striatum.

Transient ischemia was produced for 15 min by occlusion of the middle cerebral artery in halothane-anesthetized rats, and changes in the extracellular concentrations of neurotransmitter monoamines and amino acids were examined in the striatum. The occlusion produced marked increases in the extracellular concentrations of both dopamine and glutamate in the striatum in the saline-injected control group, the peak values being 148 and 5.2 times those before ischemia, respectively. Preischemic administration of histamine (200 nmol, i.c.v.) suppressed the increase in dopamine and glutamate levels during ischemia, the peak values being 38% and 40% of those in the control group, respectively. Neither the dopamine nor glutamate level was affected by 6-[2-(4-imidazolyl)ethylamino]-N-(trifluoromethylphenyl)heptanecarboxamide (HTMT), an H(1) agonist (100 nmol, i.c.v.). However, dimaprit, an H(2) agonist (100 nmol, i.c.v.) suppressed the peak values to 42% and 32%, respectively. Most neurons were degenerated 7 days after ischemia in control animals. Histologic outcome was alleviated by either histamine or dimaprit treatment, whereas HTMT did not affect the outcome. Although postischemic administration of mepyramine, an H(1) antagonist (5 nmol, i.c.v.), did not affect the histologic alleviation caused by preischemic treatment with histamine, ranitidine, an H(2) antagonist (30 nmol, i.c.v.), partly abolished the improvement caused by histamine. These results suggest that suppression of ischemic release of excitatory neurotransmitters by histamine H(2) action is a contributing factor in alleviation of histologic outcome.

Animals↗
PubMed2004

Enhancement of Na+,K(+)-ATPase and Ca(2+)-ATPase activities in multi-cycle ischemic preconditioning in rabbit hearts.

OBJECTIVE: Ischemic preconditioning (IP) has been shown to attenuate intracellular Na+ accumulation and Ca2+ overload during ischemia and reperfusion, both of which are closely related to the outcome of myocardial damage. We compared the effects of single- and four-cycle IP in Na+,K(+)-activated adenosine 5'-triphosphatase (Na+,K(+)-ATPase) and Ca(2+)-activated adenosine 5'-triphosphatase (Ca(2+)-ATPase) activities in in vivo rabbit hearts, correlating these differences to the quality of protection against subsequent ischemia. METHODS: The morphological outcome was evaluated in in vivo rabbit hearts subjected to 30 min of coronary occlusion and reperfusion for 180 min by assessing the ratio of infarct volume to risk zone volume. The effects of single- and four-cycle preconditioning ischemia were then examined. Another set of in vivo rabbit hearts was subjected to the measurement of ATPase activities at the conclusion of final preconditioning ischemia and at 60 min after reperfusion following 30 min of ischemia. RESULTS: The infarct volume was reduced by single-cycle IP to 38% of that in the control group. The four-cycle IP further reduced the infarct volume, which was 11% of that in the control group. Na+,K(+)-ATPase activity at 60 min after reperfusion in the four-cycle group was increased to 172% of that in the control group (10.8 micromol ADP/h/mg protein), whereas no difference was found in the single-cycle group. On the other hand, Ca(2+)-ATPase activity at the conclusion of IP was increased by single-cycle IP, the value being 255% of that in the control group (4.9 micromol ADP/h/mg protein). The four-cycle IP further increased the activity, and the value was 158% of that in the single-cycle group. CONCLUSIONS: Since increases in Na+,K(+)-ATPase and Ca(2+)-ATPase activities contribute to the decrease in intracellular Ca2+ concentration, the enhancement of these activities by four-cycle IP may be involved in the additional protection.

Animals↗
PubMed2003

Blockade of central histaminergic H2 receptors facilitates catecholaminergic metabolism and aggravates ischemic brain damage in the rat telencephalon.

Blockade of central H(2) receptors aggravates ischemic neuronal damage. Since changes in the activity of the monoaminergic system are contributing factors in the development of ischemic neuronal damage, the authors evaluated the effects of ranitidine on the monoaminergic system and ischemic neuronal damage in the middle cerebral artery (MCA) occlusion model of rats. Wistar rats pretreated with saline or ranitidine (3 and 30 nmol, i.c.v.) were subjected to reversible occlusion of MCA for 2 h. The total infarct volume was determined 24 h after reperfusion. The relationship between dopaminergic activity and the histologic outcome was estimated by lesioning the substantia nigra 2 days before MCA occlusion. In a second experiment, the animals were subjected to 15 min of MCA occlusion, and the effects of ranitidine on the histologic outcome was evaluated 7 days after ischemia. In a third experiment, the tissue concentrations of monoamines and their metabolites were determined in the cerebral cortex and striatum 2 h after reperfusion following MCA occlusion for 2 h. The turnover of norepinephrine and dopamine was compared between animals treated with saline and those treated with ranitidine by estimating the alpha-methyl-p-tyrosine-induced depletion of norepinephrine and dopamine, respectively. The turnover of 5-hydroxytryptamine was evaluated by the probenecid-induced accumulation of 5-hydroxyindoleacetic acid. Treatments with ranitidine markedly increased the infarct volume 24 h after reperfusion. Ranitidine also aggravated delayed neuronal death 7 days after ischemia. The aggravation was abolished by the lesion of the substantia nigra before MCA occlusion. The MCA occlusion increased the turnover of cortical norepinephrine and striatal dopamine. The turnover was further facilitated by ranitidine. Although ranitidine suppressed the 5-hydroxytryptamine turnover in the cerebral cortex, the extent of this effect was similar in both the ischemic and non-ischemic sides. These results suggest that facilitation of the catecholaminergic systems is involved in the aggravation of ischemic neuronal damage by H(2) blockade.

Animals↗
PubMed2003

Facilitation of ischemia-induced release of dopamine and neuronal damage by dexamethasone in the rat striatum.

Glucocorticoids have been reported to aggravate ischemia-induced neuronal damage in both humans and experimental animals. Because an excess release of neurotransmitters is closely related to the outcome of ischemic neuronal damage, we evaluated the effects of dexamethasone on monoaminergic release and histological outcome. Changes in the extracellular concentrations of monoamines and their metabolites in the striatum produced by occlusion of the middle cerebral artery for 20 min were measured using a microdialysis high-performance liquid chromatography procedure, and the effects of intracerebroventricular administration of dexamethasone (10 microg) were evaluated in halothane-anesthesized rats. The histological outcome was evaluated by light microscopy 7 days after ischemia. Additionally, the effects of lesioning of the substantia nigra were estimated. The extracellular concentrations of neither dopamine nor serotonin were affected by the administration of dexamethasone in the nonischemic state. The occlusion of the middle cerebral artery produced a marked increase in the extracellular concentration of dopamine in the striatum, the peak value being 240 times that before ischemia. The preischemic administration of dexamethasone enhanced the increase in dopamine level during ischemia, and the peak value in the dexamethasone group was 640% of that in the vehicle group. After 7 days, ischemic neuronal damage in the dexamethasone group was severe compared with that in the vehicle group. In rats receiving the substantia nigra lesion, the ischemic release of dopamine was abolished, and the aggravation of ischemic neuronal damage by dexamethasone was completely alleviated. Changes in the release of monoamines may be a contributing factor in the development of the ischemic neuronal damage induced by glucocorticoids.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2003

Survey of patients whose lungs could not be ventilated and whose trachea could not be intubated in university hospitals in Japan.

PURPOSE: We conducted a survey to clarify the actual circumstances in which the lungs could not be ventilated and the trachea could not be intubated (CVCI). METHODS: A questionnaire was mailed to all the university hospitals in Japan, asking about CVCI they had experienced during induction of anesthesia in 1998, and before 1997. RESULTS: Answers were obtained from 60 of 83 institutes. CVCI occurred in 26 of 151 900 cases of general anesthesia (0.017%) in 1998. Eighteen cases occurred after induction of anesthesia by several induction methods. Five cases occurred after repeated attempts at tracheal intubation by laryngoscopy and fiberscopy in patients under awake or anesthetized conditions. In the remaining 3 cases, the situation of occurrence was not documented. Patients with CVCI had anatomical abnormalities around the upper airways, mostly from acquired diseases. CVCIs after induction of anesthesia were successfully treated by restoration of spontaneous respiration, blind intubation, laryngeal mask airway, and transtracheal approaches, and CVCIs after repeated attempts at intubation were treated mostly by transtracheal approaches. No serious consequences occurred in any patients in 1998. Twenty cases were reported before 1997, and 2 were specific, in which CVCI followed malplacement of a tracheal tube, and serious consequences, death and brain damage, respectively, followed. In other patients, no serious consequences occurred, although cardiac arrest occurred in 1 patient. CONCLUSION: This survey demonstrates that CVCI can occur in any situation in which the airway is not established. Furthermore, effective treatments may be different depending on the situation, and delayed recognition of tracheal tube misplacement may lead to a serious outcome.

Adult↗
PubMed2002

Suppression of sodium pump activity and an increase in the intracellular Ca2+ concentration by dexamethasone in acidotic mouse brain.

The effects of dexamethasone on adenosine 5'-triphosphatase (ATPase) activity and the intracellular Ca(2+) concentration ([Ca(2+)](i)) were investigated in acidotic mouse brain. Dexamethasone (3 mg/kg, i.p.) or vehicle was administered 3 h before decapitation ischemia, and the brain concentration of adenosine 5'-triphosphate (ATP) was determined 0.5-2 min after ischemia. The effects of dexamethasone (0.3-3 mg/kg, i.p.) on Na(+),K(+)-activated ATPase (Na(+),K(+)-ATPase) and Ca(2+)-ATPase activities were evaluated at pH 7.4 and 6.8. Changes in [Ca(2+)](i) in an acidic medium were determined in hippocampal slices by microfluorometry using rhod-2 acetoxymethyl ester as a Ca(2+) marker, and the effects of dexamethasone (240 microg/l) was evaluated. Decapitation ischemia for 0.5 and 1 min reduced the brain ATP contents to 32% and 16% of the basal level, respectively. Dexamethasone slightly suppressed the extent of the decrease in the ATP level. Although dexamethasone did not affect Na(+),K(+)-ATPase activity at pH 7.4, the activity was suppressed by dexamethasone (3 mg/kg) to 68% at pH 6.8. The activity of Ca(2+)-ATPase was not affected by dexamethasone at either pH 7.4 or pH 6.8. When the pH of the medium of the brain slices was changed from 7.4 to 6.8, almost no increase in [Ca(2+)](i) was observed in the control group. The dexamethasone treatment increased [Ca(2+)](i) in the CA1 field and dentate gyrus immediately after induction of the acidic medium, the effect being significant after 150 s. Because anaerobic glucose metabolism in the early stage of ischemia enhances intracellular lactic acidosis, the findings may suggest a mechanism for the aggravation of ischemic neuronal damage by glucocorticoids.

Acidosis, Lactic↗
PubMed2002

Histaminergic H(2) blockade facilitates ischemic release of dopamine in gerbil striatum.

The blockade of central histaminergic H(2) receptors has been reported to aggravate ischemic neuronal damage. Since excess release of excitatory neurotransmitters is closely related to ischemic neuronal damage, the effects of ranitidine on ischemic release of dopamine were investigated in gerbil striatum. Changes in the extracellular concentration of dopamine produced by transient forebrain ischemia for 4 min were investigated by a microdialysis procedure, and the effect of intracerebroventricular administration of ranitidine (10 nmol) was evaluated. The histologic outcome was examined 7 days after ischemia by light microscopy. Forebrain ischemia produced a marked increase in the dopamine concentration in dialysates, and the level returned to the basal level after reperfusion. The preischemic administration of ranitidine enhanced the increase in the dopamine level during ischemia, and the peak value in the ranitidine group was 203% of that in the saline group. The histologic outcome was aggravated by the ranitidine treatment in the striatum, although aggravation was not observed in the cerebral cortex. The facilitation of the ischemic release of dopamine may be a contributing factor in the aggravation of ischemic damage by H(2) blockade.

3,4-Dihydroxyphenylacetic Acid↗