論文 - 高橋　慎一

Application of q-space diffusion MRI for the visualization of white matter

Fujiyoshi Kanehiro, Hikishima Keigo, Nakahara Jin, Tsuji Osahiko, Hata Junichi, Konomi Tsunehiko, Nagai Toshihiro, Shibata Shinsuke, Kaneko Shinjiro, Iwanami Akio, Momoshima Suketaka, Takahashi Shinichi, Jinzaki Masahiro, Suzuki Norihiro, Toyama Yoshiaki, Nakamura Masaya, Okano Hideyuki

Journal of Neuroscience 36 （ 9 ） 2796 - 2808 2016年03月

研究論文（学術雑誌）,  ISSN  0270-6474

　概要を見る

<p>White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders. Quantitation of non-Gaussianity for water diffusion by q-space diffusional MRI (QSI) renders biological diffusion barriers such as myelin sheaths; however, the time-consuming nature of this method hinders its clinical application. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. The heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. Histological validation of the myelin map was performed in myelin-deficient mice and in a nonhuman primate by monitoring its variation during demyelination and remyelination after chemical spinal cord injury. The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination, and remyelination in animal models. Finally, its utility in clinical practice was assessed by a pilot clinical study in a selected group of patients with multiple sclerosis (MS). The human myelin map could be obtained within 10 min with a 3 T MR scanner. Use of the myelin map was practical for visualizing white matter and it sensitively detected reappearance of myelin signals after demyelination, possibly reflecting remyelination inMSpatients. Our results together suggest that the myelin map, a kurtosis-related heat map obtainable with time-saving QSI, may be a novel and clinically useful means of visualizing myelin in the human CNS.</p>

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Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage.

Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, Moy CS, Silbergleit R, Steiner T, Suarez JI, Toyoda K, Wang Y, Yamamoto H, Yoon BW; ATACH-2 Trial Investigators and the Neurological Emergency Treatment Trials Network.

N Engl J Med. 375 （ 11 ） 1033 - 1043 2016年

研究論文（学術雑誌）, 査読有り

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Ipsilateral Facial Tactile Hypesthesia in a Patient with Lateral Medullary Syndrome

Katsumata, M., Oki, K., Nakahara, J., Izawa, Y., Abe, T., Takahashi, S. and Suzuki, N.

J Stroke Cerebrovasc Dis 2015年09月

研究論文（学術雑誌）,  ISSN  1052-3057

　概要を見る

BACKGROUND: Various sensory impairments have been reported in patients with lateral medullary syndrome, also known as Wallenberg syndrome. The typical sensory impairments experienced by patients with this condition are ipsilateral facial and contralateral trunk and limb thermal hypesthesia and hypoalgesia. Tactile (light touch) sensation is not generally diminished. Here we report the case of a 35-year-old man with lateral medullary infarction who had atypical sensory impairment. METHODS: We examined the results from the neurological examination of the patient as well as findings from computed tomography of the head and magnetic resonance imaging. RESULTS: Magnetic resonance imaging showed left lateral medullary infarction caused by left posterior inferior cerebellar artery dissection. Neurological examination revealed both tactile and thermal/pain hypesthesia on the left side of the patient's face, and thermal/pain hypesthesia on his right upper and lower limbs. CONCLUSION: There are two types of tactile sensation: epicritic and protopathic. Facial tactile sensation is usually thought to be associated with epicritic tactile sensation, which travels through principal sensory nuclei of the trigeminal nerve. The protopathic pathway travels down through the spinal tract via the trigeminal nerve and is not considered a primary pathway. However, in this case the protopathic tactile sensation pathway might be involved, and it caused facial tactile hypesthesia. Because most of previous case reports and literature reviews focused only on thermal/pain hypesthesia, we believe that this case provides critical information on the brainstem neuroanatomy, especially for the protopathic tactile sensation pathway in patients with stroke.

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Subsequent vascular events after ischemic stroke: the Japan Statin Treatment Against Recurrent Stroke-Longitudinal

Nomura, E., Suzuki, A., Inoue, I., Nakagawara, J., Takahashi, K., Takahashi, T., Manabe, Y., Yokota, C., Okada, K., Nishihara, T., Yamamoto, Y., Noda, K., Takahashi, S., Ibayashi, S., Takagi, M., Kitagawa, K., Tanahashi, N., Kuriyama, M., Hirata, K., Hosomi, N., Minematsu, K., Kobayashi, S. and Matsumoto, M.

J Stroke Cerebrovasc Dis 24 （ 2 ） 473 - 9 2015年02月

研究論文（学術雑誌）,  ISSN  1052-3057

　概要を見る

BACKGROUND: We undertook a multicenter cohort observational study to investigate the frequency and type of subsequent vascular events after an ischemic stroke and to compare the rates of vascular events between patients with and without hyperlipidemia. METHODS: This nationwide study was conducted in 19 hospitals participating in the Japan Standard Stroke Registry Study. We enrolled ischemic stroke patients, including those with a transient ischemic attack, who had not experienced any vascular events before enrollment after their ischemic stroke events. Each subject was observed prospectively from September 1, 2003, to October 1, 2005, or until a primary end point or death. Primary end points included subsequent fatal or nonfatal vascular events: stroke, angina pectoris, acute myocardial infarction, aortic aneurysm, or arteriosclerosis obliterans. RESULTS: A total of 449 patients (mean age, 67.6 years; 64.8% men) were enrolled in this study. Of the 41 vascular events observed during follow-up, 40 were stroke. The median observation period was 568 days. We found that patients with hyperlipidemia had a significantly higher rate of vascular events compared with those without hyperlipidemia according to the Kaplan-Meier method and the log-rank test (P = .013). Hyperlipidemia significantly increased the risk of vascular events (hazard ratio, 2.169 [1.125-4.312]; P = .021) according to the Cox proportional hazard model after adjusting for confounding factors (age, sex, days from ischemic stroke until enrollment, smoking habits, and daily drinking habits). CONCLUSIONS: This study demonstrated that stroke was the most common subsequent vascular event after ischemic stroke; the study also indicated that hyperlipidemia could be a risk factor for subsequent vascular events after ischemic stroke.

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パーキンソン病のVisual View　アストロサイトとドパミンニューロン

高橋, 愼一 and 馬島, 恭子

Frontiers in Parkinson Disease 8 （ 1 ） 24 - 28 2015年02月

ISSN  1883-0331

各種疾患　中毒・代謝疾患 神経細胞およびグリア細胞におけるケトン体代謝の重要性

高橋, 愼一

Annual Review神経 2015   196 - 205 2015年01月

　概要を見る

ケトン体(KB),すなわちアセト酢酸(ACA)とβヒドロキシ酪酸(BHB)は,飢餓状態やインスリン抵抗性など,グルコース利用制限がある成体脳のエネルギー基質となる.KBは肝臓において脂肪酸から合成され,授乳期の脳ではKBが主要な脳のエネルギー基質となる.またACAはミエリンの構成成分であるコレステロール合成にも利用される.エネルギー基質としてのKBは,グルコースとは異なりピルビン酸を経由せずacetyl-CoAに変換されるため,ピルビン酸脱水素酵素複合体(PDHC)を必要としない.すなわちKBは,虚血障害を受けやすいPDHCに依存せずニューロンのATP産生を可能とする.脳では内因性のKB産生も可能であり,アストログリアがその役割を担う.KBの抗てんかん作用は古くから難治性てんかんに対するケトン食療法として利用されてきたが,KBの多彩なメカニズムによる神経保護作用から,脳卒中や神経変性疾患への治療応用が期待される.BHBは好中球,マクロファージ,単球,ミクログリアに発現するナイアシン受容体(HCA2)の内因性リガンドであり,プロスタグランジンD2産生を介して神経炎症反応を抑制することで,多発性硬化症に対しても治療効果をもつ可能性がある.(著者抄録)

Cellular origin and regulation of D- and L-serine in in vitro and in vivo models of cerebral ischemia

Abe, T., Suzuki, M., Sasabe, J., Takahashi, S., Unekawa, M., Mashima, K., Iizumi, T., Hamase, K., Konno, R., Aiso, S. and Suzuki, N.

J Cereb Blood Flow Metab 34 （ 12 ） 1928 - 35 2014年12月

研究論文（学術雑誌）,  ISSN  0271-678

　概要を見る

D-Serine is known to be essential for the activation of the N-methyl-D-aspartate (NMDA) receptor in the excitation of glutamatergic neurons, which have critical roles in long-term potentiation and memory formation. D-Serine is also thought to be involved in NMDA receptor-mediated neurotoxicity. The deletion of serine racemase (SRR), which synthesizes D-serine from L-serine, was recently reported to improve ischemic damage in mouse middle cerebral artery occlusion model. However, the cell type in which this phenomenon originates and the regulatory mechanism for D-/L-serine remain elusive. The D-/L-serine content in ischemic brain increased until 20 hours after recanalization and then leveled off gradually. The results of in vitro experiments using cultured cells suggested that D-serine is derived from neurons, while L-serine seems to be released from astroglia. Immunohistochemistry studies of brain tissue after cerebral ischemia showed that SRR is expressed in neurons, and 3-phosphoglycerate dehydrogenase (3-PGDH), which synthesizes L-serine from 3-phosphoglycerate, is located in astrocytes, supporting the results of the in vitro experiments. A western blot analysis showed that neither SRR nor 3-PGDH was upregulated after cerebral ischemia. Therefore, the increase in D-/L-serine was not related to an increase in SRR or 3-PGDH, but to an increase in the substrates of SRR and 3-PGDH.

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パーキンソン病の病態とドパミンによるアストロサイトの抗酸化ストレス作用の制御機構

馬島, 恭子, 高橋, 愼一, 飯泉, 琢矢, 安部, 貴人 and 鈴木, 則宏

臨床神経学 54 （ Suppl. ） S67 2014年12月

ISSN  0009-918X

ドパミンとグルタミン酸に対するアストログリアの酸化ストレス応答の差異

馬島, 恭子, 高橋, 愼一, 飯泉, 琢矢, 安部, 貴人 and 鈴木, 則宏

脳循環代謝 26 （ 1 ） 222 2014年11月

ISSN  0915-9401

脳梗塞病態と新規治療開発 アストログリアをターゲットとした脳梗塞治療戦略の構築

高橋, 愼一

脳循環代謝 26 （ 1 ） 67 2014年11月

ISSN  0915-9401

【多発性硬化症のパラダイムシフト-病態から治療まで】 治療　フマル酸ジメチル(BG-12)

高橋, 愼一, 中原, 仁 and 鈴木, 則宏

Clinical Neuroscience 32 （ 11 ） 1287 - 1290 2014年11月

ISSN  0289-0585

Microsphere注入脳塞栓モデルにおける塞栓子径と分布の検討

塚田, 直己, 勝又, 雅裕, 大木, 宏一, 安部, 貴人, 高橋, 愼一, 伊藤, 義彰 and 鈴木, 則宏

脳循環代謝 26 （ 1 ） 226 2014年11月

ISSN  0915-9401

【最新臨床脳卒中学[下]-最新の診断と治療-】 脳梗塞各論　ラクナ梗塞　ラクナ梗塞の病態

高橋, 愼一

日本臨床 72 （ 増刊7 最新臨床脳卒中学(下) ） 155 - 158 2014年10月

ISSN  0047-1852

非典型的髄液所見を呈した硬膜下膿瘍の成人発症例

馬島, 恭子, 玉井, 直敬, 土屋, 光正, 大木, 宏一, 鈴木, 重明, 柴田, 護, 高橋, 愼一 and 鈴木, 則宏

神経免疫学 19 （ 1 ） 148 2014年09月

ISSN  0918-936X

非典型的髄液所見を呈した硬膜下膿瘍の成人発症例

馬島, 恭子, 玉井, 直敬, 土屋, 光正, 大木, 宏一, 鈴木, 重明, 柴田, 護, 高橋, 愼一 and 鈴木, 則宏

NEUROINFECTION 19 （ 2 ） 212 2014年08月

ISSN  1348-2718

脳出血にて来院し剖検で急性白血病(Cup-like AML)の診断が確定された41歳男性

勝又, 雅裕, 中原, 仁, 安部, 貴人, 内田, 理瑛, 真杉, 洋平, 高橋, 愼一 and 鈴木, 則宏

臨床神経学 54 （ 8 ） 688 2014年08月

ISSN  0009-918X

【神経診察-そのポイントと次の一手】 内科医が行う神経診察　"苦手"を攻略するコツと考え方

山脇, 正永, 高橋, 愼一, 塩尻, 俊明 and 川越, 正平

Medicina 51 （ 7 ） 1182 - 1188 2014年07月

ISSN  0025-7699

【最新臨床脳卒中学[上]-最新の診断と治療-】 病態生理　脳微小循環とNeurovascular unit　アストロサイトの立場から

高橋, 愼一

日本臨床 72 （ 増刊5 最新臨床脳卒中学(上) ） 86 - 90 2014年07月

ISSN  0047-1852

【神経診察-そのポイントと次の一手】 全身診察法

高橋, 愼一

Medicina 51 （ 7 ） 1202 - 1204 2014年07月

ISSN  0025-7699

　概要を見る

＜ポイント＞神経診察は,系統的に行う診察全体がスクリーニングであり,項目のどれかを抜粋することは病巣診断の見落としを生じる.神経診察によって得られた病巣診断が,患者の訴えや症状にどう寄与するかを考えることが疾患診断となる.神経診察によるスクリーニングが,画像,電気生理,ラボデータなどの検査の要否と緊急性を決定する指針となる.(著者抄録)

MRIを用いた中枢神経系髄鞘の可視化と多発性硬化症への応用

中原, 仁, 藤吉, 兼浩, 疋島, 啓吾, 中村, 雅也, 高橋, 慎一 and 鈴木, 則宏

日本内科学会雑誌 103 （ Suppl. ） 264 2014年02月

ISSN  0021-5384