Biomedical subjects

H Yoshioka

Publications and source records attributed to H Yoshioka.

At least 73 records · Page 4Linked to original sources

PubMed2000

Evaluation of the vestibular aqueduct in vestibulocochlear disorders by magnetic resonance imaging.

The visibility of the vestibular aqueduct (VA) was examined using magnetic resonance imaging (MRI) in 95 patients: 15 patients with Meniere's disease, 4 with vestibular Meniere's disease, 4 with cochlear Meniere's disease and 72 patients with other vestibular and/or cochlear disorders. In order to visualize the VA, the T2-weighted image (T2WI) and the proton-density weighted image (PDWI) were obtained in the sagittal plane with a head coil. The visibility of the VA was classified into 4 grades, i.e. grade 0 (not visible), grade 1 (partially visible with PDWI), grade 2 (partially visible with T2WI) and grade 3 (clearly visible with T2WI). The visibility of the VA was significantly lower bilaterally in Meniere's disease, vestibular Meniere's disease, cochlear Meniere's disease and idiopathic bilateral sensorineural hearing loss (IBSNHL) than in the other diseases. The differences among Meniere's disease, vestibular Meniere's disease and cochlear Meniere's disease were not significant. The significance of decreased visibility in IBSNHL is unknown so far. The VA studies using MRI strongly suggest that the pathogenesis of Meniere's disease, vestibular Meniere's disease, cochlear Meniere's disease and IBSNHL is, at least in part, related to the findings of the VA.

Adolescent↗

PubMed2000

Spasmolytic effects of prostaglandin E1 on serotonin-induced bronchoconstriction and pulmonary hypertension in dogs.

In this study, we simultaneously evaluated the spasmolytic effects of prostaglandin E1 (PGE1) on serotonin-induced bronchoconstriction and pulmonary hypertension. Eleven mongrel dogs (8-12 kg) anaesthetized with pentobarbital were assigned to two groups: saline (n = 4) and PGE1 (n = 7). Bronchoconstriction and pulmonary hypertension were elicited with serotonin 10 micrograms kg-1 + 1 mg kg-1 h-1 and assessed as the percentage change in bronchial cross-sectional area (BCA) measured by bronchoscopy and pulmonary vascular resistance (PVR), respectively. Thirty minutes after starting the serotonin infusion, saline or PGE1 0 (saline), 0.01, 0.1, 1.0 or 10 micrograms kg-1 i.v. was given. %BCA and %PVR (basal = 100%) were assessed before and 30 min after serotonin, and 30 and 60 min after saline (saline group) or 5 min after each dose of PGE1 (PGE1 group). In the saline group, pulmonary hypertension and bronchoconstriction were stable. In the PGE1 group, PGE1 at > or = 0.1 microgram kg-1 significantly decreased %BCA and 10 micrograms kg-1 almost fully reversed the constriction (from mean (SEM) 56.2% (4.9%) to 94.4% (3.7%)). %PVR was significantly decreased at 10 micrograms kg-1 (from 230% (24%) to 176% (11%)) only. We suggest that PGE1 may produce bronchodilation rather than pulmonary vasodilation.

Alprostadil↗

PubMed2000

Differential expression of mouse alpha5(IV) and alpha6(IV) collagen genes in epithelial basement membranes.

We first completed the primary structure of the mouse alpha5(IV) and alpha6(IV) chains, from which synthetic peptides were produced and a chain-specific monoclonal antibodies were raised. Expression of collagen IV genes in various basement membranes underlying specific organ epithelia was analyzed by immunohistochemical staining using these monoclonal antibodies and other antibodies from human and bovine sequences. It was possible to predict the presence of the three collagen IV molecules: [alpha1(IV)](2) alpha2(IV), alpha3(IV)alpha4(IV)alpha5(IV), and [alpha5(IV)](2)alpha6(IV). In skin basement membrane two of the three forms, [alpha1(IV)](2)alpha2(IV) and [alpha5(IV)](2)alpha6(IV), were detected. The alpha3(IV)alpha4(IV)alpha5(IV) molecule was observed as the major form in glomerulus, alveolus, and choroid plexus, where basement membranes function as filtering units. The molecular form [alpha5(IV)](2)alpha6(IV) was present in basement membranes in tubular organs such as the epididymis, where the tubes need to expand in diameter. Thus, the distribution of the basement membranes with different molecular composition is consistent with tissue-specific function.

Amino Acid Sequence↗

PubMed2000

Milrinone attenuates serotonin-induced pulmonary hypertension and bronchoconstriction in dogs.

UNLABELLED: We determined whether milrinone, a phosphodiesterase III inhibitor, attenuates serotonin-induced (5-hydroxytryptamine [5HT]) pulmonary hypertension (PH) and bronchoconstriction. Dogs were anesthetized with pentobarbital (30 mg/kg + 2 mg. kg(-1). h(-1)). Bronchoconstriction and PH were elicited by 5HT (10 microg/kg + 1.0 mg. kg(-1). h(-1)). Pulmonary vascular resistance was used to assess PH. Bronchoconstriction was also assessed by changes in bronchial cross-sectional area obtained from our bronchoscopic method. At 30 min after 5HT infusion started, seven dogs were given milrinone: 0 (saline), 5, 50, 500, and 5000 microg/kg at 10-min intervals. The other 12 dogs were given milrinone 5000 microg/kg 30 min after 5HT infusion, and 5 min later were given propranolol 0.2 mg/kg (n = 6) or saline (n = 6) IV. The 5HT significantly increased percentage of pulmonary vascular resistance to 208% +/- 27% and decreased percentage of bronchial cross-sectional area to 52% +/- 5% of the basal. Milrinone significantly attenuated both PH and bronchoconstriction in a dose-dependent manner. However, -log 50% effective concentration (mean ED(50) in microg/kg) of milrinone for bronchoconstriction: 4.32 +/- 0.13 (47.6) was significantly smaller than that for PH: 3.84 +/- 0.29 (144.9) (P < 0.01). In addition, the spasmolytic effects of milrinone (5000 microg/kg) were not antagonized by propranolol, although this dose significantly increased plasma catecholamines. In conclusion, milrinone attenuates 5HT-induced PH and bronchoconstriction; however, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than in pulmonary vascular smooth muscle. In addition, the relaxant effects could not be caused by beta-adrenoceptor activation because beta-blocker did not antagonize. IMPLICATIONS: We studied the effects of milrinone on serotonin-induced pulmonary hypertension and bronchoconstriction in dogs. Milrinone produces pulmonary vasodilation and bronchodilation, whose effects may not be caused by beta-adrenoceptor activation. In addition, this drug may be more sensitive to phosphodiesterase III in the airway smooth muscle than that in pulmonary vascular smooth muscle.

Animals↗

PubMed2000

A comparison of the spasmolytic effects of olprinone and aminophylline on serotonin-induced pulmonary hypertension and bronchoconstriction with or without beta-blockade in dogs.

In the present study in dogs, we compared with aminophylline the spasmolytic effects of olprinone, a novel phosphodiesterase 3 inhibitor, on serotonin-induced pulmonary hypertension (PH) and bronchoconstriction. Mongrel dogs were anesthetized with pentobarbital. PH and bronchoconstriction were induced with serotonin: 10 microg/kg + 1 mg x kg(-1) x h(-1), and assessed as % changes in pulmonary vascular resistance and bronchial cross-sectional area (basal = 100%). Initially, the relaxant effects of olprinone (n = 8: 0-1000 microg/kg) and aminophylline (n = 8: 0-100 mg/kg) were compared. Pulmonary vascular resistance and bronchial cross-sectional area were assessed before and 30 min after serotonin infusion began and 5 min after each dose of olprinone or aminophylline. We then determined whether propranolol (0.4 mg/kg) reversed the relaxation induced by olprinone (1000 microg/kg, n = 6) or aminophylline (100 mg/kg, n = 6) compared with saline (n = 6 each). Olprinone and aminophylline dose-dependently attenuated both PH and bronchoconstriction (olprinone > aminophylline: -logED(50)[mean] for PH and bronchoconstriction 5.37+/- 0.35[4.24 microg/kg] vs. 1.60+/-0.23[25.4 mg/kg] and 4.06+/-0.12[87.8 microg/kg] vs. 1.51+/-0.21[30.6 mg/kg], respectively). In addition, olprinone produced more potent pulmonary vasodilation than bronchodilation while aminophylline was equipotent. In addition, there was a significant increase in plasma catecholamines after olprinone (> or =100 microg/kg) and aminophylline (> or =10 mg/kg). With the exception of aminophylline-induced bronchodilation, propranolol did not reverse any of the other effects measured. Therefore, the spasmolytic effects of olprinone are independent of plasma catecholamines, while the bronchodilating effect of aminophylline may partially involve increased levels of circulating catecholamines.

Adrenergic beta-Antagonists↗

PubMed2000

Effects of lithium on the pharmacokinetics of valproate in rats.

Combined treatment with lithium and valproate has been used for bipolar disorder. However, the studied interaction between these two drugs has not been fully investigated. We therefore examined the effects of lithium on the pharmacokinetics (plasma disappearance, metabolism and urinary excretion) of valproate in rats. Lithium (2 mEq kg(-1)) was administered intraperitoneally twice a day for ten days. Plasma disappearance curves of valproate (50 mg kg(-1), i.v.), valproate-metabolizing activities of UDP-glucuronosyltransferase (UGT) and cytochrome P450 (CYP) in liver microsomes and urinary excretion of free valproate and valproate-glucuronide were examined. The metabolizing activity of UGT and CYP were determined by enzyme assays and a fluorescence polarization immunoassay system. Urinary valproate-glucuronide was obtained using this system by subtracting the free level from total level, which was determined after deconjugating the sample with heat and NaOH. The half-life of plasma disappearance of valproate was 25% reduced by lithium pretreatment (0.428 +/- 0.031 h with repeated lithium pretreatment vs 0.578 +/- 0.062 h for controls). The valproate-metabolizing activity of UGT and CYP were not altered by lithium although lithium increased the urinary excretion of valproate-glucuronide. In conclusion, lithium pretreatment causes a decrease in plasma valproate levels and an increase in urinary excretion of valproate-glucuronide in rats.

Animals↗

PubMed2000

Correlation of diversity of leg morphology in Gryllus bimaculatus (cricket) with divergence in dpp expression pattern during leg development.

Insects can be grouped into mainly two categories, holometabolous and hemimetabolous, according to the extent of their morphological change during metamorphosis. The three thoracic legs, for example, are known to develop through two overtly different pathways: holometabolous insects make legs through their imaginal discs, while hemimetabolous legs develop from their leg buds. Thus, how the molecular mechanisms of leg development differ from each other is an intriguing question. In the holometabolous long-germ insect, these mechanisms have been extensively studied using Drosophila melanogaster. However, little is known about the mechanism in the hemimetabolous insect. Thus, we studied leg development of the hemimetabolous short-germ insect, Gryllus bimaculatus (cricket), focusing on expression patterns of the three key signaling molecules, hedgehog (hh), wingless (wg) and decapentaplegic (dpp), which are essential during leg development in Drosophila. In Gryllus embryos, expression of hh is restricted in the posterior half of each leg bud, while dpp and wg are expressed in the dorsal and ventral sides of its anteroposterior (A/P) boundary, respectively. Their expression patterns are essentially comparable with those of the three genes in Drosophila leg imaginal discs, suggesting the existence of the common mechanism for leg pattern formation. However, we found that expression pattern of dpp was significantly divergent among Gryllus, Schistocerca (grasshopper) and Drosophila embryos, while expression patterns of hh and wg are conserved. Furthermore, the divergence was found between the pro/mesothoracic and metathoracic Gryllus leg buds. These observations imply that the divergence in the dpp expression pattern may correlate with diversity of leg morphology.

Animals↗

PubMed2000

Heat shock protein 72 expression in the right ventricle of patients undergoing congenital cardiac surgery.

While heat shock protein (HSP) 72 is known as a stress protein, there have been no reports of HSP 72 expression in patients who have undergone surgery for congenital heart disease. Fourteen patients (7 males and 7 females) who had undergone surgery for congenital heart disease were studied. The ages of the patients ranged from 2 months to 43 years old (mean 6.5 +/- 10.8 years old; median 3.0 years old). The diagnoses were Tetralogy of Fallot in seven, pulmonary atresia with ventricular septal defect (VSD) in three, complex anomalies in three, and VSD in one patient. Histological study and HSP analysis using Western blots and immunostaining with anti-HSP 72 monoclonal antibody were performed for right ventricular muscle samples resected during the surgery. The histological findings showed hypertrophic changes of ventricular cardiomyocytes in all samples studied. Western blots detected HSP 72 expression of various degrees in all specimens. Immunostaining using monoclonal antibody against HSP 72 showed that the protein was present in the nuclei and cytoplasm of cardiomyocytes. In conclusion, although it is difficult to determine the cause of the "stress" that triggers HSP 72 expression in cardiomyocytes, low O2 saturation and pressure overload might act as a "stress", and the only common factor that induced HSP 72 in every sample was hypertrophy.

Adult↗

PubMed2000

Arterioportal shunts in cirrhotic patients: evaluation of the difference between tumorous and nontumorous arterioportal shunts on MR imaging with superparamagnetic iron oxide.

OBJECTIVE: The study objective was to distinguish between the features of tumorous and nontumorous arterioportal shunts on superparamagnetic iron oxide-enhanced MR imaging in patients with cirrhosis. SUBJECTS AND METHODS: Ten arterioportal shunts in eight patients, including four tumorous and six nontumorous arterioportal shunts, were evaluated on T2-weighted turbo spin-echo and T2(*)-weighted gradient-echo sequences before and after administration of superparamagnetic iron oxide. Qualitatively, the relative signal intensity of the arterioportal shunt compared with that of the surrounding liver parenchyma was categorized into three grades: high, slightly high, and not detected. Quantitatively, signal-to-noise ratio, contrast-to-noise ratio, lesion-to-liver contrast, and percentage enhancement were calculated and compared between tumorous and nontumorous arterioportal shunts by a nonparametric statistical test (Mann-Whitney test). RESULTS: Qualitatively, all four tumorous arterioportal shunts appeared as areas of slightly high or high intensity without and with superparamagnetic iron oxide on T2-weighted turbo spin-echo images and changed from isointensity to high intensity after the administration of superparamagnetic iron oxide on T2(*)-weighted gradient-echo images. All nontumorous arterioportal shunts except one could not be recognized without or with superparamagnetic iron oxide on either sequence. Quantitatively, with superparamagnetic iron oxide the contrast-to-noise ratio and the lesion-to-liver contrast of the tumorous arterioportal shunts were significantly higher than those of the nontumorous arterioportal shunts. CONCLUSION: Tumorous arterioportal shunts are seen as areas of reduced signal loss, whereas most nontumorous arterioportal shunts are seen as areas of normal signal loss, like the normal liver parenchyma. The difference is more marked on T2(*)-weighted gradient-echo images than on T2-weighted turbo spin-echo images.

Aged↗

PubMed2000

High-resolution MR imaging of the knee at 3 T.

PURPOSE: To examine the practical feasibility of using a 3.0-T MR unit to obtain high-quality, high-resolution images of the knee joint. MATERIAL AND METHODS: One human cadaveric and 5 porcine knees were imaged with the 3.0-T unit. Sets of T1-weighted spin echo images were obtained with in-plane resolution of 0.195x0.39 mm and an acquisition time of approximately 5 min. Two porcine knees were also imaged with the 1.0-T unit with an identical imaging protocol and the signal-to-noise (S/N) ratios were measured on images at 3 T and 1 T. RESULTS: The 3-T MR system provided detailed delineation of the knees. Deep layers of the medial collateral ligament and associated fine fibers beneath the medial and lateral collateral ligament were demarcated. We observed precise demonstration of the tibial attachment of the anterior cruciate ligament, irregularity of the meniscal free edge, and conjoint tendon formation together with the lateral collateral ligament and the biceps femoris tendon. Compared to the 1-T unit, the S/N ratio with the 3-T unit was increased by a factor of 1.39 to 1.72. CONCLUSION: Due to the potential advantage of obtaining detailed images, the 3-T MR system suggests a practical utility for fine demonstration of the knee morphology.

Animals↗

PubMed2000

[Changes in MR imaging appearance of breast cancer after intra-arterial infusion chemotherapy].

The purpose of this study was to evaluate whether the characteristic change in breast cancer related to chemotherapeutic response (CR) and the effect of invasion and toxicity in the skin and pectoralis muscle exist on MR imaging after intra-arterial infusion chemotherapy. A total of 11 patients with histologically proven breast cancer underwent MR study before and after chemotherapy. Changes in images and the dynamic curve-after-chemotherapy were evaluated, including time to maximum signal intensity (SI) and the early phase enhance ratio (EPER) in the tumor. In the tumor, changes in the dynamic curve, time to maximum SI, EPER and necrosis did not correlate with CR, but change in SI on T2-weighted images was suggested to do so. Changes in the dynamic curve and images in the pectoralis muscle and in images on the skin were suggested to correlate with CR. In addition, images changed for the worse in many cases of invasion and toxicity in the pectoralis muscle and in some cases of invasion in the skin. In conclusion, tumors had fewer imaging changes correlating with CR after intra-arterial infusion chemotherapy. Changes for the worse in images of the pectoralis muscle and skin may be useful for the evaluation of invasion.

Adult↗

PubMed2000

[Multicenter study of cardiac events and anesthetic management of patients with ischemic heart diseases undergoing noncardiac surgery].

We designed a joint research project to investigate the incidence of ischemic heart diseases in patients undergoing noncardiac surgery and to define the risk of perioperative cardiac complications in these patients. Of the 8358 surgical patients in the 8 departments of anesthesiology between March 1997 and June 1997, 328 (3.9%) had ischemic heart diseases. Among the 328 patients, 54 (16.4%) developed perioperative cardiac events, including myocardial infarction (3 patients) and either lethal or potentially dangerous dysrhythmias (51 patients). Preoperative cardiac assessments were performed while the anesthetic techniques including intensive monitoring and perioperative prophylactic therapy were also employed. Patients with ischemic heart diseases received various types of preoperative evaluation to identify the degree of coronary artery disease and to assess the overall cardiac function. The patients were monitored using a multilead electrocardiogram, an arterial line, a central venous catheter, a pulmonary artery catheter, and by transesophageal echocardiography intraoperatively. Therapeutically, isosorbide, nitroglycerin, beta-blockers, calcium channel blockers, and/or nicorandil were administered to prevent perioperative ischemia. So far, no generally accepted management strategies have been established in patients with cardiovascular disorders based on large-scale outcome trials in Japan. Therefore, nationwide large multicenter trials are awaited with interest in order to establish helpful guidelines to improve the perioperative management and to reduce ischemia in cardiac patients undergoing noncardiac surgery.

Anesthesia↗

PubMed2000

[An successful case of combined daily oral administration of UFT and low-dose etoposide for multiple metastases of lung cancer].

The authors treated a 49-year old female patient, who had multiple metastases of lung cancer, by combined daily oral administration of UFT and low-dose ETP. She was admitted to our hospital due to complaints of cough and dyspnea, and multiple nodular shadows were seen in both lungs on chest X-rays. The pulmonary lesion was diagnosed as pulmonary metastasis of lung cancer (squamous cell car) by lung biopsy under CT-guide. She also had bone metastasis of the ribs and cerebellar metastasis from the lung cancer. Combination chemotherapy of UFT 300 mg/body daily and etoposide 25 mg/body daily was performed for 13 months. The pulmonary metastatic tumors were reduced significantly. No side effects of the carcinostatic agents were noted. She is now doing well. Combined daily oral administration of UFT and low-dose etoposide is considered to be safe and effective, and the treatment useful for recovering QOL in advanced lung cancer patients.

Administration, Oral↗

PubMed2000

[A multicenter study of cardiac events and anesthetic management of patients with ischemic heart diseases for noncardiac surgery--a follow-up report].

We have conducted a joint research project to investigate the incidence of ischemic heart disease in patients for noncardiac surgery and to define the risk of perioperative cardiac complications in these patients. From September to November 1997 we had 7288 patients scheduled to undergo noncardiac surgery in the 8 departments of anesthesiology. Of these patients, 228 (3.1%) patients had ischemic heart disease, and 30 of them (13.2%) developed perioperative cardiac events. Critical cardiac events, including perioperative myocardial ischemia and lethal arrhythmia, occurred in 7 of these patients. In our region of Japan, 3-4% of surgical patients tend to develop ischemic heart disease and 3.1% of them demonstrated severe cardiac complications perioperatively. Compared with United States we encounter fewer surgical patients with ischemic heart disease, but the risk of developing perioperative cardiac complications in such patients is almost the same for both countries.

Aged↗

PubMed2000

Transcatheter embolization of mycotic aneurysm of the subclavian artery with metallic coils.

Mycotic aneurysms of the subclavian artery are rare. This report describes an experience of 2 rare cases in which transcatheter embolization with metallic coils was performed for the management of these lesions alternative to surgery. Two patients who had been treated with chemotherapy for malignant neoplasms were diagnosed as having mycotic aneurysms of the left subclavian artery. The causes of these lesions were presumed to be the invasion of the arterial wall by the pulmonary abscess in case 1, and wound infection after placement of the reservoir for intraarterial chemotherapy in case 2. In both cases, proximal and distal sites of the aneurysm were embolized with metallic coils. In case 1, the vertebral artery was also embolized with Guglielmi detachable coils to avoid retrograde blood flow. Both aneurysms were completely occluded by a single embolization. In case 1, although weakness and paresthesia of the left hand remained, lethal hemoptysis due to aneurysmal fistulization to the lung parenchyma ceased. In case 2, no neurological deficit except for mild paresthesia in the left thumb had been observed. Both patients died of primary disease 10 and 5 months after the procedure. Transcatheter embolization is technically feasible and effective enough to treat the mycotic aneurysm of the subclavian artery even in the situation in which the surgical option seems to be difficult or risky.

Aneurysm, Infected↗

PubMed1999

Effects of ethanol on neuronal migration and neural cell adhesion molecules in the embryonic rat cerebral cortex: a tissue culture study.

To investigate whether ethanol has direct effects on neuronal migration in the cerebral cortex, we performed a tissue culture study using embryonic rat brain with thymidine autoradiography. After we labeled progenitor cells in the ventricular zone of E16 cerebral cortex explants with [3H]thymidine, the explants were cultured for 48 h, and then distribution of labeled cells was evaluated autoradiographically. Adding 3.0 or 6.0 mg/ml ethanol to the culture medium caused significantly decreased distribution of labeled cells in the outer intermediate [control: 2.0+/-0.6% (mean+/-S.D.); 1.0 mg/ml ethanol: 2.1+/-1.5%; 3.0 mg/ml ethanol: 0. 5+/-1.5% (P<0.05); 6.0 mg/ml ethanol: 0.4+/-0.5% (P<0.05)] and the inner intermediate-A zones [control: 19.5+/-6.2%; 1.0 mg/ml ethanol: 13.1+/-8.6%; 3.0 mg/ml ethanol: 3.0+/-3.4% (P<0.01); 6.0 mg/ml ethanol: 5.2+/-2.9% (P<0.01)] compared to the control group. The mitotic index after 48-h culture was significantly reduced in the 6. 0 mg/ml ethanol group (0.260+/-0.114%; P<0.01) compared to the control group (0.600+/-0.158%). This suggests that ethanol inhibits neuronal migration in the cerebral cortex, although prolongation of the cell cycle by ethanol may contribute to the decreased number of labeled cells in the outer intermediate and inner intermediate-A zones. Furthermore, an abnormally dense and tortuous staining pattern of immunoreactive products of N-CAM was seen on the surface of migrating neurons in the 3.0 and 6.0 mg/ml ethanol groups, while the L1 staining pattern did not differ between the control and ethanol groups. These results suggest that abnormal expression of N-CAM may be involved in the inhibition of neuronal migration by ethanol.

Animals↗

PubMed1999

Immunohistochemical nitrotyrosine distribution in neonatal rat cerebrocortical slices during and after hypoxia.

The peroxynitrite contributions to hypoxic damage in brain slices that arise from N-methyl-D-aspartate (NMDA) receptor activation were studied by following the temporal-spatial course of nitrotyrosine (NT) formation during six conditions: hypoxia (pO(2)<5 mmHg) with or without 10 microM MK-801 treatment; with exposure to 10, 100 and 1000 microM NMDA; and no treatment (control). In each experiment, twenty 350-micrometer thick cerebrocortical slices, obtained from the parietal lobes of ten 7-day-old Sprague-Dawley rats, were metabolically recovered and allowed to respire in a well-oxygenated perfusion system. Thirty minutes exposures to hypoxia or NMDA were followed by 2 h of oxygenated reperfusion. MK-801 administration began 15 min prior to hypoxia and was discontinued during reperfusion. Anti-NT serum immunohistochemistry stains in 20-micrometer frozen sections of slices taken during oxygenated reperfusion, after hypoxia or NMDA exposure, were positive in both neurons and endothelial cells. NT-positive neurons were detected sooner after hypoxia than after NMDA exposure, suggesting that mechanisms of superoxide generation were different in both groups. After hypoxia and even more so after NMDA exposure, more intense NT-positive staining was observed in endothelial cells than in neurons. Cell damage after hypoxia was attenuated by MK-801. MK-801 decreased post-hypoxia counts of NT-stained endothelial cells by 78.5% (p<0. 001) and NT-stained neurons by 54.1% (p<0.05). Our findings suggest that NMDA receptor activation in hypoxic brain slices is associated with increased post-hypoxic peroxynitrite production that contributes to acute neuronal death and endothelial cell injury. Peroxynitrite injury to endothelial cells, caused either by increased peroxynitrite from within or from increased vulnerability to peroxynitrite from without, might play an important role in hypoxic-ischemic brain injury and NMDA-induced brain injury.

Animals↗

PubMed1999

A new model of white matter injury in neonatal rats with bilateral carotid artery occlusion.

Periventricular leukomalacia is an important cause of cerebral palsy and characterized by cysts and coagulation necrosis in the periventricular white matter. Since no model of periventricular leukomalacia has been established in small animals, it is expected to establish a new model of white matter injury in immature rodents. Bilateral carotid arteries were occluded in neonatal rats at 5 days of age, and the brain neuropathologically examined at 7 days of age. Among 22 brains histologically examined, 20 (90.9%) had white matter changes including coagulation necrosis and cystic lesions in and around the internal capsule, while only two had small cerebral infarction and five showed some ischemic neurons in the cerebral cortex. Cerebral blood flow (CBF) decreased to about 25% of controls in the subcortical white matter in the animals with bilateral carotid artery occlusion (BCAO). Amyloid precursor protein (APP) immunohistochemistry demonstrated various APP-immunoreactive axonal profiles in the internal capsule and the subcortical white matter, and stronger expression of APP in pyramidal neurons in the cerebral cortex of BCAO brains. These results indicated that the white matter is more vulnerable than the cerebral cortex in 5-day-old rats when CBF decreases to about 25% and suggested that this model is useful for investigating the white matter changes induced by cerebral hypoperfusion in the neonatal brain, since previous models of hypoxic-ischemic brain injury in neonatal mice and rats revealed preferential susceptibility of the gray matter. It was also indicated that APP is a sensitive marker for mild axonal disruption in the white matter of the immature brain.

Amyloid beta-Protein Precursor↗