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H Ooboshi

Publications and source records attributed to H Ooboshi.

At least 55 records · Page 3Linked to original sources

Ischemia-induced changes in brain monoamine metabolism in aged spontaneously hypertensive rats.

Effects of aging on monoamine metabolism in transient cerebral ischemia were studied using adult and aged female spontaneously hypertensive rats (SHRs). Tissue monoamine contents in discrete brain areas were quantified after 20 min of cerebral ischemia with or without 30-min recirculation. Cerebral blood flow (CBF) was determined with a hydrogen clearance method in separate experiments. Dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) contents in the striatum, nucleus accumbens and septum decreased in ischemic aged SHRs, compared with those in ischemic adult SHRs. After 30-min recirculation, DA contents were actually unchanged with inconsistently increased DOPAC levels. Ischemic CBF decreased to < 20% of the resting CBF in the striatum and cortex, which was not different between the two age groups of SHRs. These results indicate that aging is primarily responsible for more severely impaired DA metabolism during cerebral ischemia in aged SHRs.

3,4-Dihydroxyphenylacetic Acid↗

Angiotensin converting enzyme inhibitors attenuate ischemic brain metabolism in hypertensive rats.

BACKGROUND AND PURPOSE: Angiotensin converting enzyme (ACE) inhibitors are expected to modulate neuronal activities. The present study was designed to examine the beneficial effects of ACE inhibitors on microcirculation and metabolism in the ischemic brain. METHODS: Cerebral ischemia was developed for 60 minutes in spontaneously hypertensive rats (SHR, n = 35) by bilateral carotid artery occlusion. ACE inhibitor (0.1 or 10 mg/kg SQ 29,852 or captopril) were intravenously injected 15 minutes before cerebral ischemia. Cerebral blood flow to the parietal cortex was measured with the H2 clearance technique. Lactate, pyruvate, and ATP in the brain were estimated by the enzymatic method. RESULTS: Before cerebral ischemia, high doses of both SQ 29,852 and captopril significantly decreased mean arterial pressure by 15 to 25 mm Hg and reduced cerebral vascular resistance by 13% to 17% of the resting values. Cerebral blood flow and arterial pressure during ischemia were not altered by these ACE inhibitors. After 60 minutes of cerebral ischemia, tissue lactate in vehicle-treated SHR increased 6.6-fold and ATP decreased to 65% of the control values. Administration of SQ 29,852 or captopril significantly reduced the lactate levels to 1.6- to 3.1-fold and well preserved the ATP levels to 82% to 93% of the control. CONCLUSIONS: These results suggest that inhibition of ACE activities may be protective for cerebral metabolism against ischemic insult.

Adenosine Triphosphate↗

Cerebral blood flow and ischemia-induced neurotransmitter release in the striatum of aged spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: We found age-related vulnerability to cerebral ischemia in the hippocampus and striatum in spontaneously hypertensive rats. Further study revealed that ischemia-induced release of hippocampal taurine, an inhibitory amino acid, was reduced by 40% in aged rats compared with adult rats, which suggested an impaired inhibitory function against excitotoxicity in aged rats. The purpose of this study was to examine whether ischemia-induced neurotransmitter release is altered in the striatum of aged spontaneously hypertensive rats. METHODS: Five adult (5-6 months) and five aged (18-22 months) female spontaneously hypertensive rats were subjected to 20 minutes of cerebral ischemia induced by bilateral carotid artery occlusions and 120 minutes of recirculation under amobarbital anesthesia (100 mg/kg i.p.). Cerebral blood flow was determined using the hydrogen clearance method, and extracellular concentrations of neurotransmitters were determined with the brain dialysis technique in the striatum. RESULTS: During ischemia, cerebral blood flow in aged rats decreased to 8.7 +/- 1.2 (mean +/- SEM) mL/100 g per minute (11% of the resting), which was not different from 5.2 +/- 1.7 mL/100 g per minute (8% of the resting) in adult rats, and extracellular dopamine and amino acids (glutamate, aspartate, and taurine) increased by approximately 170- and 10-30-fold, respectively, and returned to baseline after 20-40 minutes of recirculation. These values of neurotransmitters, however, were not different between aged and adult rats during ischemia and reperfusion. CONCLUSIONS: It is unlikely that a presynaptic mechanism is involved in age-related vulnerability in the striatum of hypertensive rats.

Aging↗

[Age-related changes in intracranial artery velocity measured by transcranial Doppler sonography in normotensive, hypertensive and diabetic patients].

We measured mean blood flow velocity (MFV) and Fourier pulsatility index (PI) of the M1 portion of the middle cerebral artery (MCA) by transcranial Doppler mapping technique (2 MHz, Trans-scan, EME Co., Ltd.). The correlations between these parameters and arteriosclerotic risk factors such as aging, hypertension and diabetes mellitus were examined. Healthy volunteers as well as patients suffering from hypertension and diabetes mellitus were studied. A total of 59 persons (85 MCAs) consisting of 30 males (mean age 54.4, 24-81 years) and 29 females (mean age 54.8, 20-75 years) were enrolled in this study. Some hypertensive or diabetic subjects had previous cerebrovascular disease, therefore cases who had only minor stroke or asymptomatic infarction without significant lesions in carotid artery system were included. After excluding brain embolism, these subjects were divided into three groups as normotensive/non diabetic group (NT/non DM), hypertensive group (HT) and diabetic group (DM). In each group, MFV decreased with aging, being more evident in the HT and DM groups than in the NT/non DM group. Fourier PI also showed a significant increase with aging, and the correlation was stronger than that between MFV and age. Moreover, these trends of age-Fourier PI relationship were more highly significant in HT and DM groups than NT/non DM group. In cases with HT or DM, age-related arterial changes appeared to be more severe than in those without. Fourier PI seemed valuable for detecting arterial lesions with aging, HT and DM.

Adult↗

Attenuation of ischemic and postischemic damage to brain metabolism and circulation by a novel Ca2+ channel antagonist, NC-1100, in spontaneously hypertensive rats.

We investigated the effect of a newly synthesized Ca2+ channel antagonist, NC-1100, on cerebral blood flow (CBF) and metabolism in spontaneously hypertensive rats. The rats received a bolus injection of 0.2 or 1.0 mg/kg NC-1100 i.v. and 1-h cerebral ischemia was then induced by bilateral carotid artery occlusion (group 1). The rats in group 2 were continuously infused with NC-1100 0.03 or 0.1 mg/kg per min, starting immediately after bilateral carotid artery occlusion, for the 1 h of ischemia and following 3-h recirculation. Group 1: during ischemia, CBF in all rats decreased to 6-8% of the resting values. At 1 h cerebral ischemia, brain tissue lactate increased 11.5-, 10.1- and 9.8-fold of the normal control given vehicle or NC-1100, 0.2 and 1.0 mg/kg, respectively. The ATP levels were better preserved by NC-1100 administration; 0.61 +/- 0.04 (mean +/- S.E.M.), 0.80 +/- 0.09 and 0.97 +/- 0.14 mmol/kg (P < 0.05 vs. vehicle), respectively. Group 2: during recirculation, CBF in NC-1100-treated rats returned to 83-90% of the resting values, but to only 65% in the vehicle group. Postischemic brain lactate at 3 h was less well preserved and ATP was dose dependently better preserved in NC-1100- than vehicle-treated rats. It is considered that pre- as well as postischemic administration of a Ca2+ channel antagonist, NC-1100, is beneficial to attenuate and also ameliorate the metabolic and circulatory derangement in the ischemic brain.

Adenosine Triphosphate↗

Inhibition of ischemia-induced dopamine release by omega-conotoxin, a calcium channel blocker, in the striatum of spontaneously hypertensive rats: in vivo brain dialysis study.

The effect of omega-conotoxin GVIA (CgTX), an N-and L-type voltage-sensitive calcium channel (VSCC) blocker, on the release of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum before and during transient cerebral ischemia in spontaneously hypertensive rats was studied using an in vivo brain dialysis technique. Continuous perfusion of CgTX in the striatum was started 20 min before ischemia and concentrations of dopamine and DOPAC in the dialysate were measured using HPLC with an electro-chemical detector. Before ischemia, both 10 and 100 microM CgTX significantly lowered the concentration of dopamine, to 49% of the basal values. DOPAC concentrations also decreased significantly, by 28 and 17%, respectively. Forebrain ischemia, produced by bilateral carotid artery occlusion, reduced striatal blood flow to less than 6% of the resting value in each group. During 20 min of ischemia, the vehicle group showed a marked increase in dopamine (175 times the basal concentration). In the 10 or 100 microM CgTX perfusion group, in contrast, dopamine release was significantly attenuated, to 38 or 29% of the vehicle group, respectively. DOPAC concentrations decreased during ischemia to 58% of the basal value in the vehicle group and 49% in both CgTX groups. These results indicate that the massive release of striatal dopamine during ischemia depends largely on the influx of extracellular calcium via CgTX-sensitive VSCCs.

3,4-Dihydroxyphenylacetic Acid↗

Excitatory and inhibitory amino acid changes in ischemic brain regions in spontaneously hypertensive rats.

Excitatory (glutamate, aspartate) or inhibitory amino acids (gamma-aminobutyric acid: GABA, taurine) and glutamine contents were examined in acutely induced cerebral ischemia in spontaneously hypertensive rats. At 20 min ischemia most of these amino acids remained unchanged, but glutamine significantly decreased by 14% in the CA3 hippocampal subfield. At 60 min ischemia glutamate significantly decreased by 14% in the CA3, aspartate by 17-26% in the CA3, cingulate cortex, septum and striatum. In contrast, GABA significantly increased by 48-106% in the cortices (frontal, parietal and cingulate), striatum and nucleus accumbens, but insignificantly in hippocampal subfields. Likewise, taurine increased in the parietal cortex and nucleus accumbens. Glutamine showed heterogeneous changes (increase in the nucleus accumbens and decrease in the CA3). Amino acid levels change during ischemia, but their changes are varied in each area, implying that different reaction of amino acids may explain the selective vulnerability to cerebral ischemia.

Amino Acids↗

Age-related vulnerability to cerebral ischemia in spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: We sought to determine the effects of aging on regional cerebral blood flow and ischemic brain damage in transient cerebral ischemia in rats. METHODS: Five adult (5-6 months) and five aged (18-22 months) female spontaneously hypertensive rats were subjected to 20 minutes of bilateral carotid occlusion and 60 minutes of recirculation under amobarbital anesthesia (100 mg/kg i.p.). Regional cerebral blood flow in the hippocampus and striatum was measured using the hydrogen clearance method. Nine adult and 14 aged rats were subjected to 20 minutes of bilateral carotid occlusion or were sham-operated under ether anesthesia. Seven days after 20 minutes of cerebral ischemia, the rats' brains were perfusion fixed. Ischemic damage in the hippocampus and striatum was graded (0 [normal] to 3 [majority of neurons damaged]). RESULTS: After 20 minutes of bilateral carotid occlusion, striatal cerebral blood flow decreased to 9.1 +/- 1.5 and 3.9 +/- 2.0 ml/100 g/min in aged and adult rats, respectively, and hippocampal cerebral blood flow decreased to 8.6 +/- 2.4 and 5.7 +/- 2.4 in aged and adult rats, respectively. Although these ischemic cerebral blood flow values were not significantly different between the two age groups, scores for ischemic damage in the hippocampus CA-1 subfield and striatum were significantly higher in aged than in adult rats (p less than 0.05, Kruskal-Wallis' h test with Bonferroni correction). CONCLUSIONS: We conclude that aging may be a primary factor in the development of greater ischemic neuronal damage observed in aged hypertensive rats.

Aging↗

Acute effects of antihypertensive agents on cerebral blood flow in hypertensive rats.

The acute effects of various antihypertensive agents on cerebral blood flow and mean arterial pressure (MAP) were studied in anesthetized (amobarbital 100 mg/kg) spontaneously hypertensive rats. Cerebral blood flow in the cortex and thalamus was measured by the hydrogen clearance method before and during a 60-min i.v. infusion of calcium antagonist (nifedipine), angiotensin converting enzyme inhibitor (captopril) or beta-blocker (propranolol). Nifedipine, 30 or 150 micrograms/kg per h, decreased dose dependently the MAP by 20 or 31%, and concomitantly increased cortical blood flow by 28 or 74%, and thalamic blood flow by 51 or 64%, respectively. Captopril, 10 or 100 mg/kg per h, decreased MAP by 7 or 14%, but changed cerebral blood flow minimally. In contrast, propranolol, 1.0 or 5.0 mg/kg per h, decreased MAP by 13 or 11%, with a concomitant reduction of cortical and thalamic blood flow by 20 or 15 and 33 or 37%, respectively. It is concluded that the changes in cerebral blood flow in response to hypotension are varied by antihypertensive drugs depending on the direct or indirect effect of the drugs (dilatation or constriction) on cerebral vessels. Nifedipine seems to dilate while propranolol constricts cerebral vessels.

Animals↗

Ischemic flow threshold for striatal dopamine release in rats.

To determine the level of cerebral blood flow reduction which causes striatal dopamine release, extracellular dopamine and cerebral blood flow was simultaneously determined using in vivo brain dialysis and a hydrogen clearance method, respectively, in the striatum of spontaneously hypertensive rats before and during experimental cerebral ischemia. The ischemic flow threshold for neurotransmitter dopamine release was found to be 20% of the resting value or 8-10 ml/100g/min of cerebral blood flow, being similar to those for energy and membrane failures.

Animals↗

Regional distribution of DNA and RNA in rat brain: a sensitive determination using high-performance liquid chromatography with electrochemical detection.

DNA and RNA contents in 20 brain regions or nuclei of the rat were determined by a highly sensitive method using high-performance liquid chromatography with electrochemical detection. The high DNA and RNA contents were found in the hypothalamic nuclei, especially the median eminence-arcuate nucleus. These results may be available for the preparation of nucleic acids as the regional control.

Amygdala↗

Primary intraventricular hemorrhage imaged by high-field magnetic resonance imaging--a case report.

Primary intraventricular hemorrhage (PIVH) imaged by magnetic resonance imaging (MRI) is reported. A fifty-seven-year-old man with long-standing hypertension suddenly developed severe headache, vomiting, and retrograde amnesia. A computed tomography scan on the same day revealed hematoma in the right posterior horn of the lateral ventricle and in the 4th ventricle. Angiography of the neck and head failed to demonstrate any vascular abnormalities. On the second day his neurological symptoms almost recovered except for the loss of the memory of the ictal day. High-field MRI on the sixteenth day demonstrated an isointense lesion surrounded by a hypointense area in the T1 weighted image or a hyperintense lesion in the T2 weighted image, suggesting subacute hematoma consistent with hypertension, just anterior to the right trigone of the lateral ventricle.

Cerebral Hemorrhage↗

Striatal glutamic acid and gamma-aminobutyric acid in transient cerebral ischemia in spontaneously hypertensive rats.

A massive striatal dopamine release (241-fold increase) was observed in a previous study during acute cerebral ischemia in rats. In this study, extracellular levels of glutamic acid (GLU), gamma-aminobutyric acid (GABA) and lactic acid were simultaneously determined using in vivo brain dialysis in the striatum of spontaneously hypertensive rats during cerebral ischemia and after recirculation. Extracellular GABA levels increased to 932 +/- 75% (mean +/- SEM) of the resting level and GLU increased to 390 +/- 63% during 20 min ischemia. Although ischemia-induced release of GLU and GABA was demonstrated in this study, the degree of increase was smaller than that of dopamine. These findings may be relevant to the pathophysiology of cerebral ischemia in the striatum.

Animals↗

[Effects of alpha- and beta-adrenergic blockers on the lower limits of cerebral blood flow autoregulation in spontaneously hypertensive rats].

The effects of alpha- and beta-adrenergic blockers (phenoxybenzamine, PBZ and propranolol, PPL, respectively) on the cerebral (CBF) and cerebellar (CeBF) blood flow autoregulations were examined in spontaneously hypertensive rats. CBF and CeBF were measured during stepwise hemorrhagic hypotension using hydrogen clearance method. The lower limits of autoregulation for CBF beyond which blood flow was decreased steeply were 72% of the resting blood pressure level in the control, 56% in the PBZ treated group, and 80% in the PPL group. Similar tendency was observed in CeBF. These results indicate that PBZ leads to a downward shift while PPL to a slight upward shift of the lower limits of CBF and CeBF autoregulations, suggesting that alpha-adrenergic blockade has a favorable effect for the maintenance of cerebral blood flow during acute reduction of blood pressure.

Adrenergic alpha-Antagonists↗

Effect of thromboxane synthetase inhibitor on cerebral circulation and metabolism during experimental cerebral ischemia in spontaneously hypertensive rats.

The protective effect of thromboxane synthetase inhibitor, OKY-046, on brain ischemia was studied in spontaneously hypertensive rats. Cerebral ischemia was developed by bilateral carotid artery ligation (BCL) for 1 or 3 h and thereafter, circulation was restored for 15 min. OKY-046, 5 or 30 mg/kg, or saline as control was administered i.v. before BCL. Neither blood pressure nor blood gases were altered by OKY-046 or saline injection. During BCL, cerebral cortical blood flow was reduced to 25 and 15% of the resting value at 30 and 60 min, respectively, and these changes were not different among the groups. In rats with ischemia longer than 1 h, the blood flow was well preserved by OKY-046, 30 mg/kg, to 10-17% of the resting level, thus significantly higher than that (less than 5%) in non-treated rats. After 15 min recirculation, the supratentorial lactate level was lower and adenosine triphosphate (ATP) was higher in OKY-046-treated rats than in the saline-treated ischemic rats. Plasma thromboxane B2 was increased markedly in 1 h ischemic-reperfused rats without treatment and the increase was almost completely inhibited by OKY-046. In contrast, 6-keto-prostaglandin F1 alpha was increased 8.5-fold after ischemia and the increase was not affected by the treatment. OKY-046 seems to have an antiischemic effect on acutely induced cerebral ischemia. Selective inhibition of thromboxane A2 production and an inversely high level of prostaglandin I2 may be an important contribution to protection of the microcirculation during ischemia and preservation of ischemic cerebral metabolism.

Adenosine Triphosphate↗

Determination of guanine by high-performance liquid chromatography with electrochemical detection: application to DNA and RNA assays.

A highly sensitive assay for guanine was developed using high-performance liquid chromatography with electrochemical detection (ECD). Guanine was susceptible to the electrochemical oxidation, and ECD response was proportional to the amount of guanine in the range 0.25-4 pmol of guanine. The ECD of guanine was applicable to the analysis of nucleic acids. DNA and RNA were hydrolyzed in 0.03 and 3 M HCl, respectively, and guanine liberated from the nucleic acids was separated on a reverse-phase column and determined by ECD. The method allowed detection of 0.2 ng of calf thymus DNA or tRNA. An application of the method is shown for DNA and RNA assays in trichloroacetic acid extracts of rat adrenal and liver.

Adrenal Glands↗

Mortality and histological findings of the brain during and after cerebral ischemia in male and female spontaneously hypertensive rats.

Mortality and pathological changes of the brain during and after cerebral ischemia induced by bilateral carotid artery occlusion (BCO) were studied in male and female spontaneously hypertensive rats (SHR). Systolic arterial blood pressure at rest was significantly higher in male SHR (228 +/- 13 mm Hg, mean +/- S.E.M.) than female (192 +/- 12) (P less than 0.05). The average survival time during permanent occlusion was 11 +/- 6 h (mean +/- S.D.) in male SHR and 17 +/- 7 in female (P less than 0.005), though the cumulative mortality during 24-h ischemia was not different between male (88%) and female SHR (84%). Severe ischemic changes of nerve cells in the brain, especially in the cortex and hippocampus, were observed in 50% of male SHR at 3-h ischemia, while only 15% was observed in female SHR even after 7-h ischemia. After the temporary ischemia followed by reperfusion for 24 h, the mortality was varied between male and female SHR; 0, 31 and 100% after 1-, 3- and 5-h ischemia, respectively, in male SHR and 0% after 1- to 3-h ischemia and 33% after 5- to 7-h ischemia, respectively, in female. Ischemic changes of the brain tissue, such as acidophilic cytoplasm, nuclear degeneration and intercellular edema, were more frequent and severe in male SHR than female after recirculation following 3- or 5-h ischemia. It is concluded that the mortality and post-ischemic viability seem to be determined by the duration of ischemia and also by the degree of the neuronal damage, and female SHR is more tolerated for ischemic insult in comparison to male SHR.

Animals↗