研究者詳細 - 高橋　慎一

論文 - 高橋　慎一

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ラット中大脳動脈閉塞再灌流後のmonocarboxylate transporters発現の経時的変化

安部, 貴人, 鈴木, 重明, 高橋, 慎一 and 鈴木, 則宏

脳卒中 27 （ 1 ） 166 2005年04月

ISSN 0912-0726

化膿性髄膜炎として発症した脳塞栓症,上肢動脈塞栓症を合併した感染性心内膜炎の1救命例

安富, 大祐, 高橋, 慎一, 石川, 美江, 石川, 士郎, 村山, 晃 and 朝見, 淳規

日本内科学会関東地方会 525回 24 2005年03月

細胞外K+濃度上昇がラット培養アストログリアのエネルギー基質利用率に与える影響

安部, 貴人, 高橋, 慎一 and 鈴木, 則宏

脳循環代謝 17 （ 1 ） 83 - 84 2005年03月

ISSN 0915-9401

生理的範囲での[K+]oの変化がアストロサイトのエネルギー基質利用率に与える影響を検討した.更に高グルコース(22mM)DMEMと低グルコース(2mM)DMEMで培養したアストログリアの反応の差異についても検討した.尚,アストログリアは新生仔Sprague-Dawleyラット大脳皮質より組織を採取し培養を行った.1)グルコース2mM下で培養した細胞では,22mMに比べ[14C]lactate酸化率の上昇を認めた.[14C]deoxyglucoseリン酸化率は変化しなかった.2)細胞外K+濃度の上昇により,培養アストログリアの[14C]deoxyglucoseリン酸化率は増加し,[14C]lactate 酸化率は変化しなかった.3)神経活動亢進時に放出されるK+を介し,アストロサイトの解糖系エネルギー消費のみが亢進する可能性が示唆された

成長ホルモン分泌不全性低身長症としてホルモン補充療法をうけていたMELASの一例

安富, 大祐 and 高橋, 慎一

臨床神経学 45 （ 2 ） 152 2005年02月

ISSN 0009-918X

【内科医が診るしびれと痛み】　しびれと痛みに対する対症療法　その他の薬物治療

高橋, 慎一

Medicina 41 （ 8 ） 1369 - 1371 2004年08月

ISSN 0025-7699

救急医療における二次医療機関の役割

芳賀, 佳之, 高橋, 慎一, 奥井, 俊一, 鈴木, 暁, 山藤, 和夫, 藤田, 亨介, 村山, 晃, 川越, 光博, 遠藤, 昌夫 and 戸倉, 康之

埼玉県医学会雑誌 38 （ 3 ） 304 - 307 2003年12月

ISSN 0389-0899

細胞内グリコーゲン量の変化がアストログリアのエネルギー代謝に与える影響:Alamar Blue還元法による検討

安部, 貴人, 高橋, 慎一 and 福内, 靖男

脳卒中 25 （ 1 ） 159 2003年03月

ISSN 0912-0726

頸部整体中に延髄内側症候群(Dejerine症候群)を発症した椎骨動脈解離の1例

横田, 淳一, 天草, 弥生, 冨田, 裕 and 高橋, 慎一

脳と神経 55 （ 2 ） 121 - 125 2003年02月

ISSN 0006-8969

38歳男.頸部整体治療中に突然,右片麻痺,深部感覚障害および左舌下神経麻痺を発症した.脳血管撮影およびMR angiographyにて左椎骨動脈の狭窄,不整拡張などが認められた.MRI上,延髄左内側部に梗塞巣が確認され,延髄内側梗塞と診断された.発症機序としては,頸部整体術による頸部回旋運動で椎骨動脈に過度に伸展,圧排が加わることにより血管内膜損傷を生じ,動脈解離を引き起こすことにより虚血に陥り,延髄梗塞を発症したと考えられた.臨床経過は全般的に改善傾向がみられ約2ヵ月半後退院となったが,右上肢麻痺の改善は認められなかった.本症の発症を少しでも未然に防ぐには,整体術を受ける前に頭頸部を静かに回旋,過伸展させた状態でいったん経過観察し,何らかの異常を訴える場合は即時中止すべきである

Reduction of Alamar Blue, a novel redox indicator, is dependent on both the glycolytic and oxidative metabolism of glucose in rat cultured neurons

Abe, T., Takahashi, S. and Fukuuchi, Y.

Neurosci Lett 326 （ 3 ） 179 - 82 2002年07月

ISSN 0304-3940

Recently, it has been hypothesized that neurons mainly utilize lactate produced by astrocytes to generate energy (i.e. ATP). Regardless of numerous studies, whether lactate rather than glucose fuels neurons in vivo remains a matter of controversy. In the present study we have examined the substrate-preference of the reduction of Alamar Blue, a novel redox indicator, by cultured rat astroglia and neurons. Alamar Blue reduction is dependent on cellular reducing equivalents. Therefore, the substrate-preference of Alamar Blue reduction could reflect that for cellular energy production. Rates of Alamar Blue reduction by 2 mM glucose were two-fold higher in astroglia than those in neurons. Alamar Blue reduction induced by 2 mM lactate was 78% of that by 2 mM glucose in neurons while only 20% in astroglia. Nevertheless, glucose elicited larger Alamar Blue reduction than lactate both in astroglia and neurons. These results indicate that neuronal energy production in vivo depends on both the glycolytic and oxidative metabolism of glucose even though astroglia rely on glycolysis as has been reported.

Substrate-dependence of reduction of MTT: a tetrazolium dye differs in cultured astroglia and neurons

Takahashi, S., Abe, T., Gotoh, J. and Fukuuchi, Y.

Neurochem Int 40 （ 5 ） 441 - 8 2002年04月

ISSN 0197-0186

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction is widely used to evaluate cell proliferation and viability. MTT reduction is interpreted to be indicative of cellular metabolic activity, and the site of reduction includes both mitochondrial and cytosolic redox reactions. Astrocytes are believed to rely mainly on glycolysis for ATP generation, whereas neurons are considered to depend more on oxidative metabolism. The present study, therefore, tested the substrate-preference of glucose and its metabolites for MTT reduction in cultures of rat type 1 astroglia and neurons.MTT specific activity of astroglia was much higher than that of neurons. Astroglial MTT reducing activity in glucose-free medium or 2mM glucose with iodoacetate (5mM) was completely blocked. In glucose-depleted medium, 2mM lactate, pyruvate, malate, or acetate elicited minimal increases in MTT reduction by astroglia. In contrast, MTT reducing activity in neurons was enhanced two-fold by pyruvate and the reducing activity of lactate was equivalent to that of glucose, while malate had a small and acetate had no effect on MTT reduction. These results indicate that these two cell types differ markedly in their substrate-preferences for MTT reduction. In astroglia, MTT reduction reflects mainly cytosolic redox activity and is dependent on glyceraldehyde-3-phosphate dehydrogenase. In neurons, pyruvate dehydrogenase supports MTT reduction more effectively than glucose or lactate, even though both of these substrates can produce NADH and pyruvate.

Becker型筋ジストロフィーの症候性保因者の一例

岸林, 潤, 谷田部, 可奈, 川村, 潤, 石原, 傳幸 and 高橋, 慎一

臨床神経学 41 （ 6 ） 341 2001年06月

ISSN 0009-918X

Astroglial cell death induced by excessive influx of sodium ions

Takahashi, S., Shibata, M., Gotoh, J. and Fukuuchi, Y.

Eur J Pharmacol 408 （ 2 ） 127 - 35 2000年11月

ISSN 0014-2999

Na(+) influx has been implicated to play an important role in the mechanisms of neuronal cell damage under ischemia as well as in neurodegenerative disorders. Thus far, however, the effects of Na(+) influx on astrocytic damage have not been studied extensively. In the present study, we have examined the effects of Na(+) influx induced by veratridine (Na(+) channel opener), monensin (Na(+) ionophore), and glutamate (co-transportation with Na(+)) on rat cultured astroglial damage. Cells were incubated with bicarbonate buffer with 25 mM glucose containing either 100 microM veratridine, 10 microM monensin, or 1 mM glutamate with or without 1 mM ouabain for 20 h. Cellular damage was evaluated quantitatively by lactate dehydrogenase (LDH) release or 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction. Veratridine, monensin, or glutamate alone did not induce significant astroglial damage. Veratridine and monensin co-incubated with ouabain, which inhibits active extrusion of Na(+) by Na(+),K(+)-ATPase, thereby enhances intracellular Na(+) accumulation, caused significant cell death (P<0. 001, approximately 50% cell damage), whereas glutamate did not. Na(+)-free solution substituted by choline (impermeable cation) attenuated cell damage induced by veratridine and monensin markedly, while Li(+) substitution (permeable cation) rather exacerbated. Nifedipine (100 microM), a blocker of L-type Ca(2+) channel, reduced veratridine-induced glial damage by 50%. Neither bepridil nor benzamil, a blocker of Na(+)-Ca(2+) exchanger, had any protection. Cyclosporin A (1 or 10 microM), an inhibitor of mitochondrial permeability transition or 10 microM N-benzyloxycarbonyl-Val-Ala-Asp-(O-methyl)fluoromethyl ketone (zVAD-fmk), which inhibits a broad range of caspases, did not show protective effects.

【眼で見る神経内科】　粟粒結核症に随伴した多発性中枢神経結核腫

高橋, 慎一 and 植松, 大輔

神経内科 53 （ Suppl.2 ） 60 - 61 2000年09月

ISSN 0386-9709

【浮腫の病態と治療】　浮腫の病態と治療　脳循環異常にみる浮腫

高橋, 慎一 and 福内, 靖男

医学と薬学 43 （ 5 ） 927 - 933 2000年05月

ISSN 0389-3898

MTT還元反応から見たラット培養アストログリアとニューロンのエネルギー代謝

高橋, 慎一, 後藤, 淳 and 福内, 靖男

脳循環代謝 12 （ 1 ） 93 - 94 2000年04月

ISSN 0915-9401

Role of sodium ion influx in depolarization-induced neuronal cell death by high KCI or veratridine

Takahashi, S., Shibata, M. and Fukuuchi, Y.

Eur J Pharmacol 372 （ 3 ） 297 - 304 1999年05月

ISSN 0014-2999

Intracellular Na+ concentration plays an important role in the regulation of cellular energy metabolism; i.e., increased intracellular Na+ concentration stimulates glucose utilization both in cultured neurons and astrocytes. Both high KCI and veratridine, which have been known to cause neuronal damage, elicit increased glucose utilization, presumably via increased intracellular Na+ concentration. In the present study, we examined the role of intracellular Na+ influx in the mechanisms of neuronal cell damage induced by high KCl or veratridine assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric method. Rat primary cultures of striatal neurons were incubated with high KCl (final concentrations: 25, 50 mM) or veratridine (0.1-100 microM) with or without various inhibitors. High KCl depolarizes cell membrane, thus, leading to Na+ influx through an activation of voltage-sensitive Na+ channels, while veratridine elicits Na+ influx by directly opening these channels. After 24-h incubation with elevated [K+]o or veratridine, glucose contents in the medium decreased significantly (approximately by 7 mM), but remained higher than 18 mM. High [K+]o reduced percent cell viability significantly (approximately 50% at 25 mM, approximately 40% at 50 mM [K+]o, P<0.01), but tetrodotoxin (100 nM) had no protective effect, indicating that Na+ influx was not essential to high K+ -induced cell death. DL-2-Amino-5-phosponovaleric acid (APV) (1 mM) completely blocked cell death induced by elevated [K+]o, while 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (10 microM) did not. In contrast, veratridine (>10 microM) caused cell damage in a dose-dependent and tetrodotoxin-sensitive manner, but none of APV, CNQX, or bepridil (Na+ -Ca2+ exchanger blocker) had any protective effect. Nifedipine (50 approximately 100 microM), however, reduced percent cell damage induced by veratridine.

肺炎球菌による髄膜炎を契機に発症した急性散在性脳脊髄炎の1例

菊池, 敬, 高橋, 慎一, 植松, 大輔, 藤田, 功 and 竹内, 東太郎

埼玉県医学会雑誌 33 （ 6 ） 886 - 889 1999年03月

ISSN 0389-0899

ラット初代培養線条体ニューロンの脱分極性細胞死とそのメカニズム

高橋, 慎一 and 他

脳卒中 20 （ 1 ） 114 1998年02月

ISSN 0912-0726

Effects of increased extracellular potassium on influx of sodium ions in cultured rat astroglia and neurons

Takahashi, S., Shibata, M. and Fukuuchi, Y.

Brain Res Dev Brain Res 104 （ 1-2 ） 111 - 7 1997年12月

ISSN 0165-3806

Membrane depolarization by elevated extracellular K+ concentration ([K+]o) causes rapid Na+ influx through voltage-sensitive Na+ channels into excitable cells. The consequent increases in intracellular Na+ concentration ([Na+]i) and/or [K+]o stimulate Na+,K+-ATPase activity, which in turn stimulates energy metabolism and rates of glucose utilization (CMR[glc]) in neurons. We previously reported that in cultured cells elevated [K+]o stimulated CMR(glc) in neurons but not astroglia; but increasing [Na+]i by opening voltage-sensitive Na+ channels with veratridine stimulated CMR(glc) in both. These results indicated that Na+ influx plays a key role in the regulation of energy metabolism in neurons and astroglia, but that depolarization of astroglial membranes by elevated [K+]o does not open voltage-sensitive Na+ channels as it does in neurons. To examine this possibility directly we have measured the effects of increased [K+]o and of veratridine on Na+ influx into cultured rat astroglia and neurons. Cells were incubated in bicarbonate buffer containing ouabain (1 mM), tracer amounts of 22NaCl, and various concentrations (5.4, 28, 56 mM) of K+ or 75 microM veratridine for 0-60 min. Cells were digested and assayed for intracellular 22Na+ content. Elevated extracellular K+ stimulated tetrodotoxin-sensitive 22Na+ accumulation in cultured neurons but inhibited 22Na+ influx in astroglia. Veratridine-stimulated Na+ influx in both astroglia and neurons (144% and 133%, respectively), and these effects were completely blocked by 10 microM tetrodotoxin. These results indicate that increased [K+]o does not open voltage-sensitive Na+ channels and may inhibit Na+ influx in astroglia.

Examination of potential mechanisms in the enhancement of cerebral blood flow by hypoglycemia and pharmacological doses of deoxyglucose

Horinaka, N., Artz, N., Jehle, J., Takahashi, S., Kennedy, C. and Sokoloff, L.

J Cereb Blood Flow Metab 17 （ 1 ） 54 - 63 1997年01月

ISSN 0271-678X

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 mM, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3- concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 mM) or pharmacological doses of deoxyglucose.

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高橋 慎一

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高橋　慎一

論文 - 高橋　慎一