Biomedical subjects
Publications and source records attributed to S Nagao.
We report two cases with triggering at the distal end of the A2 pulley. One was caused by enlargement of the flexor digitorum profundus (FDP) tendon and the other by enlargement of both slips of the flexor digitorum superficialis (FDS) tendon. Both were relieved by reduction tenoplasty and short releases, or venting, of the distal A2 pulley.
Adaptation of ocular reflexes is a prototype of motor learning. While the cerebellum is acknowledged as the critical site for motor learning, the functional differences between the cerebellar cortex and nuclei in motor memory formation are not precisely known. Two different views are proposed: one that the memory is formed within the cerebellar flocculus, and the other that the memory is formed within vestibular nuclei. Here we developed a new paradigm of long-term adaptation of mouse horizontal optokinetic response eye movements and examined the location of its memory trace. We also tested the role of flocculus and inferior olive in long-term adaptation by chronic lesion experiments. Reversible bilateral flocculus shutdown with local application of 0.5 microl-5% lidocaine extinguished the memory trace of day-long adaptation, while it very little affected the memory trace of week-long adaptation. The responsiveness of vestibular nuclei after week-long adaptation was examined by measuring the extracellular field responses to the electrical stimulation of vestibular nerve under trichloroacetaldehyde anesthesia. The amplitudes and slopes of evoked monosynaptic field response (N1) of week-long adapted mice were enhanced around the medial vestibular nucleus compared with those of control mice. Chronic flocculus or inferior olive lesions abolished both day and week-long adaptations. These results suggest that the functional memory trace of short-term adaptation is formed initially within the cerebellar cortex, and later transferred to vestibular nuclei to be consolidated to a long-term memory. Both day and week-long adaptations were markedly depressed when neural nitric oxide was pharmacologically blocked locally and when neuronal nitric oxide synthase was ablated by gene knockout, suggesting that cerebellar long-term depression underlies both acquisition and consolidation of motor memory.
The purpose of this study was to examine the possibility of neuronal remodeling and repair after cold injury-induced brain edema using immunoassays of nestin, 3CB2, and TUC-4. Male ddN strain mice were subjected to cold-induced cortical injury. Animals were divided into the following 6 groups: 1) 1-day after injury, 2) 1-week after injury, 3) 2-weeks after injury, 4) 1-month after injury, 5) sham, and 6) normal controls. Brain water content measurement, Western blot analysis, histological examination, and neurobehavioral examination were performed. Brain water content was significantly increased in the ipsilateral cortex at 1-day after injury. At 1-day and 1-week after injury, immunoreactivity of nestin, 3CB2, and TUC-4 were absent. Nestin was expressed in 3CB2-positive astrocytes at 1-month after injury, and nestin expression with TUC-4 was present in the hippocampal cell layer. Neurobehavioral function of the 1-month after injury group was significantly improved compared with function 1-day after injury. These results suggest that delayed precursor cell marker expression in glia and neuron-like cells might be part of adaptation to the injury. Although brain injury causes brain edema and neuronal death, there is the possibility of remodeling.
We investigated the occurrence of DNA damage in brain after intracerebral hemorrhage (ICH) and the role of iron in such injury. Male Sprague-Dawley rats received an infusion of 100 microL autologous whole blood or 30 microL FeCl2 into the right basal ganglia and were sacrificed 1, 3, or 7 days later. 8-hydroxyl-2'-deoxyguanosine (8-OHdG) was analyzed by immunohistochemistry, while the number of apurinic/apyrimidinic abasic sites (AP sites) was also quantified. 8-OHdG and AP sites are two hallmarks of DNA oxidation. DNA damage was also examined using PANT and TUNEL labeling. Dinitrophenyl (DNP) was measured by Western blot to compare the time course of protein oxidative damage to that of DNA. DNA repair APE/Ref-1 and Ku-proteins were also measured by Western blot. Bipyridine, a ferrous iron chelator, was used to examine the role of iron in ICH-induced oxidative brain injury. An increase in 8-OHdG, AP sites, and DNP levels, and a decrease in APE/Ref-1 and Ku levels were observed. Abundant PANT-positive cells were also observed in the perihematomal area 3 days after ICH. Bipyridine attenuated ICH-induced changes in PANT and DNP. These results suggest that iron-induced oxidation causes DNA damage in brain after ICH and that iron is a therapeutic target for ICH.
Neurological deterioration during the first day after intracerebral hemorrhage (ICH) is associated with early hematoma growth in 18 to 38% of patients. While clinical studies continue to evaluate efficacy of activated recombinant factor VII (rFVlla) for reducing frequency of early hematoma growth, there have been no studies investigating the effect of rFVIIa on early hematoma growth. We used a collagenase-induced ICH model in the rat to evaluate the effects of rFVIIa on early hematoma growth. Two hours after injection of 0.14 U of type IV bacterial collagenase in 10 microL of saline into the basal ganglia, a small amount of blood collected in the striatum. The ICH gradually increased in size, extending posteriorly to the thalamus by 24 hours after injection. Intravenous administration of rFVIIa immediately after collagenase injection decreased average hematoma volume at 24 hours compared with vehicle-treated group (168.1 +/- 13.4 mm3 vs. 118.3 +/- 23.0 mm3, p < 0.01). There was also a decrease in total hemoglobin content in rats treated with rFVlla compared with vehicle-treated rats (optical density at 550 nm: 0.87 +/- 0.08 vs. 0.71 +/- 0.09, p < 0.05). There was no difference in cortical brain water content overlying the hematoma between the rFVlla- and vehicle-treated groups (81.4 +/- 0.7% vs. 81.7 +/- 0.4%). Our study indicates that treatment with rFVIla may be useful in reducing the frequency of early hematoma growth in ICH patients.
The present study examined differences in intracerebral hemorrhage (ICH)-induced brain injury in male and female rats, whether delayed administration of 17beta-estradiol can reduce ICH-induced brain damage, and whether these effects are estrogen receptor (ER)-dependent. Male and female Sprague-Dawley rats received an infusion of 100-microL autologous whole blood into the right basal ganglia. The effects of 1beta-estradiol (5 mg/kg, i.p.) on ICH-induced brain injury were examined by measuring brain edema and neurological deficits 24 hours later. Heme oxygenase-1 (HO-1) was investigated by immuno-analysis. Brain edema was significantly less in female compared to male rats. The ER antagonist ICI182,780 exacerbated ICH-induced brain edema in female but not in male rats, suggesting that ER activation during ICH is protective in female rats. Administration of 17beta-estradiol to male (but not female) rats significantly reduced brain edema, neurological deficits, and ICH-induced increases in brain HO-1 levels when given 2 hours after ICH. This study showed that female rats have less ICH-induced injury than male rats. ER is involved in limiting ICH-induced injury in female rats. ICH-injury in male rats can be reduced by 17beta-estradiol. Since 17beta-estradiol treatment was effective in male rats, it could be a potential therapeutic agent for ICH.
The present study is aimed to clarify the postoperative outcome of endoscopic carpal tunnel release in elderly patients with carpal tunnel syndrome. Endoscopic carpal tunnel release was performed on 37 hands of 27 patients (2 men, 25 women) who were aged 70 years or older and clinically and electrophysiologically diagnosed with carpal tunnel syndrome. Mean age at the time of surgery was 74.5 years (range: 70-85 years). Mean postoperative follow-up was 35.5 months (range: 12-114 months). Pain was present preoperatively in 20 hands, but quickly resolved postoperatively in all cases. Numbness completely disappeared in 13 of 37 hands (35.1%), but some degree of numbness remained in the remaining cases. Preoperative severity of thenar muscle atrophy was none in 4 hands, mild in 7 hands, moderate in 12 hands and severe in 14 hands. Postoperative severity of thenar muscle atrophy at final follow-up was none in 13 hands, mild in 16 hands, moderate in 2 hands and severe in 6 hands, confirming that thenar muscle atrophy improves even in elderly patients. However, moderate or severe thenar muscle atrophy remained in 8 hands (21.6%). Endoscopic carpal tunnel release should be considered in the elderly, even though clinical symptoms may not improve substantially in advanced cases.
BACKGROUND AND AIMS: 1.4-Dihydroxy-2-naphthoic acid (DHNA), a bifidogenic growth stimulator from Propionibacterium freudenreichii, is thought to have a beneficial effect as a prebiotic; however, its in vivo effect on intestinal inflammation remains unknown. The aim of this study was to determine whether oral administration of DHNA can ameliorate dextran sodium sulphate (DSS) induced colitis and to determine the possible underlying mechanisms. METHOD: Colitis was induced in mice by treatment with 2.0% DSS for seven days. DHNA (0.6 or 2.0 mg/kg) was given in drinking water prior to (preventive study) or after (therapeutic study) DSS administration. Colonic damage was histologically scored, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression and beta7 positive cell infiltration were determined by immunohistochemistry. mRNA levels of proinflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumour necrosis factor alpha (TNF-alpha)) were determined by quantitative real time polymerase chain reaction. In addition, bacterial flora in the caecum, concentrations of short chain acids, and luminal pH were examined. RESULTS: DHNA improved survival rate and histological damage score in mice administered DSS in both the preventive and therapeutic studies. DHNA significantly attenuated the enhanced expression of MAdCAM-1, the increased beta7 positive cell number, and the increased mRNA levels of IL-1beta, IL-6, and TNF-alpha in DSS treated colon. In addition, the decreased number of Lactobacillus and Enterobacteriaceae induced by DSS was recovered by DHNA. Preventive effects on decrease in butyrate concentration and decrease in pH level in mice administered DSS were also observed in the DHNA preventive study. CONCLUSION: DHNA, a novel type of prebiotic, attenuates colonic inflammation not only by balancing intestinal bacterial flora but also by suppressing lymphocyte infiltration through reduction of MAdCAM-1.
Intracerebral hemorrhage (ICH) induces brain edema formation via a variety of mechanisms including toxicity due to thrombin and erythrocyte lysis. However, the roles of oxidative damage and excitotoxicity have not been fully elucidated and they are examined in this rat ICH study. Adult male Sprague-Dawley rats received an intracaudate injection of 100 microl autologous whole blood and 5 U of thrombin. Rats were sacrificed at 1 hour, 1 and 3 days, and then the brains processed using Western blotting to quantify N-methyl-D-aspartate receptor (NR) subunit expression. At 3 days, animals were also sacrificed for assessment of protein oxidation using Western blot analysis for dinitrophenyl (DNP) and brain water content. Compared to the contralateral side, ipsilateral basal ganglia NR1 and NR2A subunit expression transiently increased at 1 hour after ICH and thrombin injection. From 24 hours there was a marked down-regulation. At 3 days, marked edema and DNP up-regulation were observed in ICH and thrombin injection groups. The present NR expression up-regulation at 1 hour may reflect the acute cell response after ICH. The down-regulation of NR subunits and upregulation of DNP may be associated with cell damage, towards which thrombin may contribute.
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The aetiology of Crohn's disease (CD) remains unknown. Since SAMP1/Yit mice have been reported to develop CD-like spontaneous enteric inflammation, such mice have been studied as an animal model of CD. In this study, using this model we examined T lymphocyte migration in microvessels of intestinal mucosa in vivo and the expression of adhesion molecules by immunohistochemistry. Fluorescence-labelled T lymphocytes isolated from AKR/J (control) mice were injected into the tail veins of recipient mice, and T lymphocyte migration in the postcapillary venules of Peyer's patches, submucosal microvessels, and villus capillaries of the terminal ileum was monitored using an intravital microscope. Adhesion of T lymphocytes was significantly increased in 35 week old SAMP1/Yit mice compared with that in AKR/J or 15 week old SAMP1/Yit mice. Immunohistochemical study showed increased infiltration of CD4, CD8 and beta7-integrin-positive cells and increased expression of MAdCAM-1 and VCAM-1 in the terminal ileum of SAMP1/Yit mice. Antibodies against MAdCAM-1 and VCAM-1 significantly inhibited adhesion of T lymphocytes to microvessels of the terminal ileum, and anti-MAdCAM-1 antibody showed stronger suppressive effect than the anti-VCAM-1 antibody. Periodical administration of anti-MAdCAM-1 antibody twice a week for 7 weeks significantly ameliorated ileitis of SAMP1/Yit mice, but submucosal hypertrophy was not significantly suppressed. Anti-VCAM-1 antibody treatment failed to show significant resolution of ileitis. In addition, anti-MAdCAM-1 antibody treatment also attenuated established ileitis. The results demonstrate that, although MAdCAM-1 and VCAM-1 play an important role in T lymphocyte-endothelial cell interactions in SAMP1/Yit mice, MAdCAM-1 may be a more appropriate target for therapeutic modulation of chronic ileitis.
Although monocyte-endothelial cell interactions represent an initial step in controlling the recruitment of monocytes in inflamed tissues, their dynamic processes in microvessels of lymphoid (Peyer's patches) and non-lymphoid (villus) regions in gut-associated lymphoid tissue remain poorly understood. We monitored the migration of fluorescence-labelled monocytes derived from the spleen in intestinal microvessels with or without lipopolysaccharide (LPS) treatment and investigated the role of adhesion molecules, P-selectin, vascular cell adhesion molecule (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). In control mice, there were few interactions between infused monocytes and the endothelium of intestinal microvessels. The monocyte-endothelial interactions (both rolling and adhesion) were significantly increased in intestinal microvessels of LPS-treated mice compared with those in controls. Anti-P-selectin monoclonal antibody (MoAb) significantly suppressed the LPS-induced increase in monocyte rolling in postcapillary venules of Peyer's patches and submucosal venules. Anti-VCAM-1 MoAbs significantly suppressed the LPS-induced increase in monocyte adhesion to postcapillary venules (PCVs) of Peyer's patches, submucosal venules, and villus capillaries. In contrast, anti-ICAM-1 MoAb significantly suppressed the number of adherent monocytes in PCV of Peyer's patches but not in submucosal venules or villus capillaries. These observations demonstrated that LPS treatment resulted in a significant increase in recruitment of monocytes both in microvessels of lymphoid and non-lymphoid regions and that P-selectin, VCAM-1 and ICAM-1 appeared to play important roles in LPS-induced interactions.
Blood-brain barrier (BBB) disruption is a critical event leading to vasogenic brain edema and secondary brain damage after cold injury-induced brain trauma. Matrix metalloproteinases (MMPs) are implicated in BBB disruption in this model. The purpose of this study was to examine the effects of MMI270, a synthetic nonspecific MMP inhibitor, on cold injury-induced brain edema in rats. Treatment with MMI270, a bolus injection at a dose of 30 mg/kg, was started immediately after the induction of cold injury and was continued at a dose of 40 mg/kg/day using an intraperitoneal osmotic minipump. At 24 hours after the cold injury, the brain water content and the BBB permeability to Evans Blue (EB) were determined. The secondary brain lesion was assessed using hematoxylin and eosin (H-E) staining at 7 days after the cold injury. Compared with the untreated control group, treatment with MMI270 significantly reduced the brain water content in the ipsilateral core and intermediate areas and protected the BBB integrity to EB in the ipsilateral core area. The secondary lesion was significantly smaller in the MMI270-treated animals compared with the untreated animals. Our results indicate that treatment with MMI270 in rats exhibits protection in acute brain edema formation and secondary brain lesion by attenuating the BBB permeability after cold injury.
Studies indicate that thrombin plays an important role in intracerebral hemorrhage (ICH) induced edema formation. However, the time window for administration of a thrombin inhibitor to reduce ICH-induced edema is unknown. Nor is it known whether this time window extends beyond the period when a thrombin inhibitor might exacerbate rebleeding. This study examines whether a thrombin inhibitor, argatroban, can reduce edema formation following intracerebral infusion of 100 microl of blood in the rat, the therapeutic time window for argatroban, and whether argatroban promotes rebleeding. Intracerebral injection of argatroban 3 hours after ICH caused a significant reduction in edema measured at 48 hours. The systemic administration of argatroban (0.9 mg/h) starting 6 hours after ICH also significantly reduced edema formation. There was no protection when the onset of argatroban administration was delayed to 24 hours after ICH. Argatroban did not increase collagenase-induced hematoma volume when given into the clot after 3 hours or given systemically at 6 hours. Our data suggest argatroban may be an effective therapy for ICH-induced edema.
Recent studies indicate that inflammatory reaction occurs around hematoma after intracerebral hemorrhage (ICH). In this study the authors examine the hypothesis that overexpression of IL-1ra in the brain attenuate brain edema formation after ICH. Adenoviruses expressing IL-1ra (Ad.RSVIL-1ra) or LacZ (Ad.RSVLacZ) or saline were injected into the lateral ventricle. On the fifth day after virus injection, 100 microl of autologous blood or 5 U thrombin was infused into the right basal ganglia. Rats with ICH were killed 24 or 72 hours later for measurement of brain water content. Thrombin-treated rats were killed 24 hours later for edema measurements and an assessment of polymorphonuclear leukocyte (PMNL) infiltration by myeloperoxidase (MPO) assay. Compared with control groups, Ad.RSVIL-1ra treated rats had less brain edema formation in the ipsilateral basal ganglia 3 days after ICH (81.5 +/- 0.3% compared with 83.4 +/- 0.4% and 83.3 +/- 0.5% in control animals). Ad.RSVIL-1ra treated rats had also less brain edema following thrombin injection. The reduction of brain edema induced by thrombin was involved in the reduction of PMNL infiltration in basal ganglia, as assessed by MPO assay. Adenovirus-mediated overexpression of IL-1ra attenuated brain edema formation following ICH, perhaps by reduction of thrombin-induced brain inflammation.
BACKGROUND: The purpose of the present study was to examine the influence of cooling and rewarming conditions using an accurate brain temperature control system. METHOD: The brain temperature of animals was measured with a thermometer while feedback regulation was achieved with a cold (4( degrees )C) and hot (50( degrees )C) water on-off flow system. Brain temperature was well controlled throughout the experiment by using both cold water and hot water simultaneously. Three groups were studied, as follows: 1) the standard group (cooled to 24( degrees )C for 1 hour, kept at 24( degrees )C for 2 hours and rewarmed to 37( degrees )C for 1 hour), 2) the rapid-cooling group (cooled to 24( degrees )C for 30 min, kept at 24( degrees )C for 2 h, and rewarmed to 37( degrees )C for 1 h), 3) the rapid-rewarming group (cooled to 24( degrees )C for 1 h, kept at 24( degrees )C for 2 h, and rewarmed to 37( degrees )C for 30 min) and the normal-control group. FINDINGS: An increase of MAP-2 immunoreactivity of the CA1 neurons in the dorsal hippocampus was observed one week but not one month after hypothermia in the rapid-rewarming group. There was also a significant increase in the glutamate and lactate value at the end of rewarming compared with the baseline in the rapid-rewarming group (p<0.01). INTERPRETATION: Our results suggest that rapid rewarming after hypothermia triggered an uncoupling of cerebral circulation and metabolism, inducing an increase of extracellular glutamate and lactate, consequently reversible neuronal cell damage.
In order to investigate influences of discharge rates on fluvial transport behavior of elements in the Kuji River, Japan, suspended and dissolved phase concentrations in the river water were measured together with the water flow rates. The concentrations of suspended particulate matter (SPM) increased by two or three orders of magnitude with the water discharge, and also had seasonal variations. Adsorptive elements or heavy metal elements, which tend to form insoluble compounds, were present generally as suspended forms in the river waters, and their dissolved form concentrations tended to increase with the water discharge. On the other hand, non-adsorptive elements such as alkali and alkaline-earth elements were present as dissolved forms under a normal flow rate condition, but equivalent quantity of suspended species also occurred under a high flow condition. In this case, the dissolved form concentrations decreased with the water discharge. Characterization of SPM with analyses of chemical compositions, scanning electron microscopy (SEM) and X-ray diffractometry (XRD) indicated that clay mineral such as montmorillonite would be the main carrier material of trace and major elements during the fluvial transport in the Kuji River. Variations of contents of selected elements in SPM with the water discharge indicated that river bottom sediments, which are probably potential sources of SPM added due to high water flow rates, would be different in chemical compositions from SPM floating under a normal flow condition. Variations of chemical compositions of SPM as well as of suspended or dissolved form concentrations of elements in the river waters were formulated as a function of the water discharge rates.
There are two different proposals regarding the role of the cerebellar flocculus in the adaptation of the vestibulo-ocular reflex: that the flocculus is the site for both the induction and retention of the adaptation, or that the flocculus plays an important role in the induction, but the vestibular nuclei to which the flocculus issues its efferents are the site of retention. To locate the memory trace for the adaptation of the vestibulo-ocular reflex, we determined effects of acute pharmacological shutdown of the bilateral cerebellar flocculi in four Macaca fuscata. The gain of the horizontal vestibulo-ocular reflex was measured by sinusoidal oscillation of the turntable by 10 degrees (peak-to-peak) at 0.33 Hz in the dark. Two hours of 0.33 Hz-10 degrees sinusoidal oscillation of the turntable while viewing the stationary checked-pattern screen through a x2.2 magnifying lens adaptively increased the horizontal vestibulo-ocular reflex gain by 0.2 on the average. The gain increase lasted for 1 h when the monkeys were left with their heads fixed in darkness, but it disappeared within 24 h after the monkeys were returned to their cages where they had free movements. The effects of injections of 5 or 10% lidocaine chloride into the bilateral floccular areas (8 microl for each side) immediately after adaptation occurred were determined in nine sessions. The gain of the horizontal vestibulo-ocular reflex immediately decreased to the level before the adaptation. These effects of lidocaine lasted for at least 1 h. On the contrary, injections of the same amount of Ringer's solution, tested in eight sessions, hardly affected gain of the horizontal vestibulo-ocular reflex over 1-h period. These depressant effects of lidocaine injections were specific to the gains increased by adaptation. These results suggest that the memory trace for the short-term adaptation of the horizontal vestibulo-ocular reflex gain induced by 2 h of sustained visual-vestibular interactions resides within the flocculus.