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  1995年

  札幌医科大学  

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• 医学博士

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• 　

  　

  　

  日本脳神経外科学会

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  The Japan Stroke Society

• 　

  　

  　

  Japan Neurosurgical Society

• 　

  　

  　

  Japanese Association for Acute Medicine

• 　

  　

  　

  日本脊髄外科学会

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• ライフサイエンス   脳神経外科学  

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• 札幌医科大学   附属病院 脳神経外科学講座   講師  

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• 脳神経外科学

• 脳卒中

• 外傷

• 脊髄外科

• 神経科学

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• Deep learning from head CT scans to predict elevated intracranial pressure.

  Ryota Sato, Yukinori Akiyama, Takeshi Mikami, Ayumu Yamaoka, Chie Kamada, Kyoya Sakashita, Yasuhiro Takahashi, Yusuke Kimura, Katsuya Komatsu, Nobuhiro Mikuni

  Journal of neuroimaging : official journal of the American Society of Neuroimaging    2024年10月  [国際誌]

  　概要を見る

  BACKGROUND AND PURPOSE: Elevated intracranial pressure (ICP) resulting from severe head injury or stroke poses a risk of secondary brain injury that requires neurosurgical intervention. However, currently available noninvasive monitoring techniques for predicting ICP are not sufficiently advanced. We aimed to develop a minimally invasive ICP prediction model using simple CT images to prevent secondary brain injury caused by elevated ICP. METHODS: We used the following three methods to determine the presence or absence of elevated ICP using midbrain-level CT images: (1) a deep learning model created using the Python (PY) programming language; (2) a model based on cistern narrowing and scaling of brainstem deformities and presence of hydrocephalus, analyzed using the statistical tool Prediction One (PO); and (3) identification of ICP by senior residents (SRs). We compared the accuracy of the validation and test data using fivefold cross-validation and visualized or quantified the areas of interest in the models. RESULTS: The accuracy of the validation data for the PY, PO, and SR methods was 83.68% (83.42%-85.13%), 85.71% (73.81%-88.10%), and 66.67% (55.96%-72.62%), respectively. Significant differences in accuracy were observed between the PY and SR methods. Test data accuracy was 77.27% (70.45%-77.2%), 84.09% (75.00%-85.23%), and 61.36% (56.82%-68.18%), respectively. CONCLUSIONS: Overall, the outcomes suggest that these newly developed models may be valuable tools for the rapid and accurate detection of elevated ICP in clinical practice. These models can easily be applied to other sites, as a single CT image at the midbrain level can provide a highly accurate diagnosis.

  DOI PubMed

• Combined endoscopic endonasal and transcranial approach for internal carotid artery aneurysms: usefulness and safety of endonasal proximal control.

  Ryota Sato, Yukinori Akiyama, Takeshi Mikami, Yuka Kawata, Chie Kamada, Yusuke Kimura, Katsuya Komatsu, Nobuhiro Mikuni

  Neurosurgical review   46 ( 1 ) 283 - 283  2023年10月  [国際誌]

  　概要を見る

  It is necessary to secure both the proximal and distal sides of the parent artery to prevent premature rupture when clipping cerebral aneurysms. Herein, we describe four cases in which the proximal internal carotid artery (ICA), affected by a paraclinoid aneurysm, was secured using an endoscopic endonasal approach. We used various tools, including a surgical video, cadaver dissection picture, artist's illustration, and intraoperative photographs, to elucidate the process. No patient experienced postoperative complications at our institution. Compared to the cervical or cavernous ICA, the ICA adjacent to the clivus (paraclival ICA) can be anatomically safely and easily exposed using an endoscopic endonasal approach because there is no need to consider cerebrospinal fluid leakage or hemorrhage from the cavernous sinus. Securing the proximal side of the parent artery using an endoscopic endonasal approach may be a viable method for clipping selected ICA aneurysms, such as paraclinoid aneurysms especially for upward or outward aneurysms of the C2 portion.

  DOI PubMed

• Microbleeds Due to Reperfusion Enhance Early Seizures after Carotid Ligation in a Rat Ischemic Model.

  Takuro Saito, Takeshi Mikami, Tsukasa Hirano, Hiroshi Nagahama, Rei Enatsu, Katsuya Komatsu, Satoshi Okawa, Yukinori Akiyama, Nobuhiro Mikuni

  Neurologia medico-chirurgica   63 ( 6 ) 228 - 235  2023年06月  [国内誌]

  　概要を見る

  Impaired reperfusion in ischemic brain disease is a condition that we are increasingly confronted with owing to recent advances in reperfusion therapy. In the present study, rat models of reperfusion were investigated to determine the causes of acute seizures using magnetic resonance imaging (MRI) and histopathological specimens. Rat models of bilateral common carotid artery ligation followed by reperfusion and complete occlusion were created. We compared the incidence of seizures, mortality within 24 h, MRI, and magnetic resonance spectroscopy (MRS) to evaluate ischemic or hemorrhagic changes and metabolites in the brain parenchyma. In addition, the histopathological specimens were compared with those observed on MRI. In multivariate analysis, the predictive factors of mortality were seizure (odds ratios (OR), 106.572), reperfusion or occlusion (OR, 0.056), and the apparent diffusion coefficient value of the striatum (OR, 0.396). The predictive factors of a convulsive seizure were reperfusion or occlusion (OR, 0.007) and the number of round-shaped hyposignals (RHS) on susceptibility-weighted imaging (SWI) (OR, 2.072). The incidence of convulsive seizures was significantly correlated with the number of RHS in the reperfusion model. RHS on SWI was confirmed pathologically as microbleeds in the extravasation of the brain parenchyma and was distributed around the hippocampus and cingulum bundle. MRS analysis showed that the N-acetyl aspartate level was significantly lower in the reperfusion group than in the occlusion group. In the reperfusion model, RHS on SWI was a risk factor for convulsive seizures. The location of the RHS also influenced the incidence of convulsive seizures.

  DOI PubMed

• Computational Fluid Dynamics Analysis Features in Aneurysm Development in Rats.

  Shoichi Komura, Katsuya Komatsu, Takeshi Mikami, Yukinori Akiyama, Sangnyon Kim, Rei Enatsu, Hiroshi Nagahama, Nobuhiro Mikuni

  Neurologia medico-chirurgica   63 ( 6 ) 250 - 257  2023年06月  [国内誌]

  　概要を見る

  The investigation of how to control the development and growth of cerebral aneurysms is important for the prevention of subarachnoid hemorrhage. Although there have been several types of research studies on computational fluid dynamics (CFD) analysis of brain aneurysm development and growth, there has been no unified interpretation of the CFD analysis results. The purpose of this study is to clarify the characteristics of CFD analysis results related to the development of cerebral aneurysms using an animal model. Nineteen rat models of cerebral aneurysms were created, and the CFD analysis results between the cerebral aneurysm group [n = 10; the aneurysm was observed on magnetic resonance angiography (MRA) within 10 weeks after aneurysm induction surgery] and the nonaneurysm group (n = 9) were compared. All aneurysms were confirmed on the proximal segment of the left cerebral artery (P1), and the cross-sectional area and curvature of the left P1 were evaluated together. In the cerebral aneurysm group, there was a decrease in wall shear stress (WSS) that is consistent with the location of the aneurysm compared to the nonaneurysm group. The cross-sectional area of the left P1 gradually increased in the aneurysm group but not in the nonaneurysm group. The mean curvature in the entire left P1 was higher in the aneurysm group than in the nonaneurysm group. This study revealed that the development of cerebral aneurysms is due to changes in vascular morphology, namely, an increase in vessel diameter and a high curvature, and a decreased WSS consistent with the site of aneurysm development using this animal model.

  DOI PubMed

• Transcranial electrical stimulation technique for induction of unilateral motor evoked potentials.

  Shoto Yamada, Rei Enatsu, Shu Ishikawa, Yusuke Kimura, Katsuya Komatsu, Tomohiro Chaki, Yukinori Akiyama, Takeshi Mikami, Nobuhiro Mikuni

  Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology   150   194 - 196  2023年06月  [国際誌]

  　概要を見る

  OBJECTIVE: Transcranial electrical stimulation motor evoked potentials (TES-MEP) are widely used to monitor motor function; however, broad current spread and induced body movement are limitations of this technique. We herein report a localized stimulation technique for TES-MEP that induces unilateral MEP responses. METHODS: The stimulation of C1(+)-C4(-) or C2(+)-C3(-) was performed to induce right- or left-sided muscle contraction, respectively, in 70 patients. Electromyography was recorded by placing electrodes on the bilateral abductor pollicis brevis (APB) and abductor hallucis (AH) muscles. Stimulation conditions were regulated in the range to induce unilateral muscle contractions contralateral to the anodal stimulation. The thresholds and amplitudes of TES-MEP were retrospectively analyzed. RESULTS: The thresholds of APB were lower than those of AH in 47 patients, AH thresholds were lower than those of APB in 6 patients, and both APB and AH started to respond at the same intensity in 15 patients. This technical stimulation induced contralateral limb contractions with a suprathreshold stimulation of 129.4 ± 35.6 mA (mean ± standard deviation) in 68 patients (97%). Amplitudes in the suprathreshold stimulation of APB and AH responses were 727.5 ± 695.7 and 403.3 ± 325.7 μV, respectively. CONCLUSIONS: The C1(+)-C4/C2(+)-C3(-) stimulation in TES-MEP enables a localized stimulation to induce unilateral MEP responses. SIGNIFICANCE: Our stimulation technique enables the stable and safe monitoring of unilateral limbs, and contributes to the reliable monitoring of motor function in neurosurgery.

  DOI PubMed

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• Trastuzumab Based Chemotherapy in Two Patients with HER2-Positive Metastatic Carcinoma ex Pleomorphic Adenoma

  Yohei Arihara, Kazuyuki Murase, Kohichi Takada, Naotaka Hayasaka, Shogo Miura, Koji Miyanishi, Masayoshi Kobune, Makoto Kurose, Yukinori Akiyama, Junji Kato

  ANNALS OF ONCOLOGY ( OXFORD UNIV PRESS )  27  2016年07月

  研究発表ペーパー・要旨（国際会議）  

• 副鼻腔・頭蓋底原発clear cell carcinomaの1例

  鈴木健吾, 鰐渕昌彦, 秋山幸功, 池田潤, 南田善弘, 長谷川匡, 寳金清博, 三國信啓

  Neurol Surg   40 ( 7 ) 617 - 621  2012年07月

  　概要を見る

  We described a case of primary clear cell carcinoma (CCC) of the paranasal cavity and skull base. A 59-year-old female experienced chronic nasal obstruction and double vision. Computed tomography (CT) scan revealed a mass lesion of the paranasal cavity, reaching the skull base and intracranial zone. We performed a biopsy by endonasal endoscopic surgery and pathological examinations revealed the tumor was a clear cell carcinoma. No primary tumor was identified on evaluation of the whole body by CT scan and FDG-PET ( 18fluorodeoxy glucose positron emission tomography) scan, so we diagnosed a primary CCC of the paranasal cavity. We decided to use stereotactic radiation therapy. Neurologically, her diplopia was improved. The patient is well at 2 years of follow-up with no evidence of local enlargement. There are some reports about the metastatic sinonasal CCC, but there are few reports about primary nasal and sinonasal CCC. This is the fourth case report of primary nasal and sinonasal CCC.

  PubMed J-GLOBAL

• Integration of engrafted Schwann cells into injured peripheral nerve: Axonal association and nodal formation on regenerated axons

  C Radtke, Y Akiyama, KL Lankford, PM Vogt, DS Krause, JD Kocsis

  NEUROSCIENCE LETTERS ( ELSEVIER IRELAND LTD )  387 ( 2 ) 85 - 89  2005年10月

  　概要を見る

  Transplantation of myelin-forming cells can remyelinate axons, but little is known of the sodium channel organization of axons myelinated by donor cells. Sciatic nerve axons of female wild type mice were transected by a crush injury and Schwann cells (SCs) from green fluorescence protein (GFP)-expressing male mice were transplanted adjacent to the crush site. The male donor cells were identified by GFP fluorescence and fluorescence in situ hybridization (FISH) for Y chromosome. In nerves of GFP-expressing mice, GFP was observed in the axoplasm and in the cytoplasmic compartments of the Schwann cells, but not in the myelin. Following transplantation of GFP-SCs into crushed nerve of wild type mice, immuno-electron microscopic analysis indicated that GFP was observed in the cytoplasmic compartments of engrafted Schwann cells which formed myelin. Nodal and paranodal regions of the axons myelinated by the GFP-SCs were identified by Na-v 1.6 sodium channel and Caspr immunostaining, respectively. Nuclear identification of the Y chromosome by FISH confirmed the donor origin of the myelin-forming cells. These results indicate that engrafted GFP-SCs participate in myelination of regenerated peripheral nerve fibers and that Na-v 1.6 sodium channel, which is the dominant sodium channel at normal nodes, is reconstituted on the regenerated axons. (C) 2005 Elsevier Ireland Ltd. All rights reserved.

  DOI

• Autologous transplantation of expanded neural precursor cells into the demyelinated monkey spinal cord

  S Oka, O Honmou, Y Akiyama, M Sasaki, K Houkin, K Hashi, JD Kocsis

  BRAIN RESEARCH ( ELSEVIER SCIENCE BV )  1030 ( 1 ) 94 - 102  2004年12月

  　概要を見る

  The objective of this study was to establish if neural precursor cells could safely be developed from biopsy of the subventricular zone (SVZ) in the non-human primate (marmoset), and to determine their myelinating potential after autologous transplantation into a demyelinated lesion. Small amounts of tissue were safely collected from the subventricular-subependymal zone of the adult primate brain under ultrasonography without any neurological deficit. Neural precursor cells were isolated and expanded in the presence of mitogen in vitro. The dorsal columns of the adult marmoset spinal cord were demyelinated by X-irradiation and intraspinal injections of ethidium bromide in the center of the radiation field. Cell suspensions of the neural precursors were microinjected through a micropipette into the demyelinated lesion site in the spinal cord. Lesions were histologically examined 3 weeks after transplantation. Light and electron microscopic examination of plastic embedded sections revealed a significant number of myelinating profiles in the transplantation zone; no myelination was observed in control lesions. The myelinated axons had predominantly peripheral patterns of myelination. These results demonstrate that autologous transplantation of neural precursor cells in the adult nonhuman primate can remyelinate demyelinated central nervous system (CNS) axons, thus suggesting the potential utility of such an approach in demyelinating lesions in humans. (C) 2004 Elsevier B.V. All rights reserved.

  DOI

• Neural precursors as a cell source to repair the demyelinated spinal cord

  JD Kocsis, Y Akiyama, C Radtke

  JOURNAL OF NEUROTRAUMA ( MARY ANN LIEBERT INC PUBL )  21 ( 4 ) 441 - 449  2004年04月

  　概要を見る

  Schwann cells and neural precursor cells derived from adult human brain (subventricular zone) and from bone marrow were studied anatomically and physiologically after transplantation into the demyelinated rat spinal cord. All cell types formed myelin and restored conduction velocity. Following transection of the dorsal funiculus, Schwann cells and olfactory ensheathing cells facilitated axonal regeneration and restoration of conduction across the lesion site. There is discussion on the challenges of cell type selection and preparation for a potential clinical cell therapy study in human demyelinating diseases.

  DOI

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共同研究・競争的資金等の研究課題 【 表示 ／ 非表示 】

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• Functional Connectivity解析による脳記憶機能地図の解明

  基盤研究(C)

  研究期間:

  2022年04月

  -

  2025年03月

   

  千葉 遼平, 秋山 幸功, 三國 信啓

• 中枢神経Glymphatic systemの機能解明と新たな認知症治療薬の開発

  基盤研究(C)

  研究期間:

  2021年04月

  -

  2024年03月

   

  秋山 幸功, 三上 毅, 三國 信啓, 石合 純夫

  　研究概要を見る

  Glymphatic systemの機能障害は様々な脳疾患を引き起こすと考えられている。とくに認知機能には大きな影響を与えると考えられており、その治療法の開発を行う。 方法：マウスを用いてGlymphatic systemのdrainage部分である静脈の閉塞モデルの作成を行い、その認知機能障害の進行、程度を評価する。静脈は側副血行路が発達していることが多いため、両側内・外頚静脈閉塞モデルを作成する予定である。 モデル作成後動物用7.0 Tesla-MRIを用いて静脈のうっ滞、MR spectroscopyにて脳実質内代謝産物の定量を行う。 結果：静脈結紮モデルを安定して作成することに成功した。静脈非閉塞のコントロールモデルと比較して、頭蓋内静脈の拡大を認め、眼球の突出などが認められたモデルも存在し、頭蓋内圧亢進状態が得られた。 考察：両側内・外頚静脈閉塞モデルは頭蓋内圧亢進モデルとして確立できるものと考えられ、今後頭蓋内圧亢進状態が高次機能へどのように影響を与えるか、また、髄液ドレナージなどによる頭蓋内圧降下療法がその高次機能障害を抑制できるか評価したいと考えている。

• 線維芽細胞に着目したくも膜炎症の分子機構の解明と新たな脳保護薬の開発

  基盤研究(C)

  研究期間:

  2020年04月

  -

  2023年03月

   

  三上 毅, 鈴木 比女, 秋山 幸功, 三國 信啓, 小松 克也, 平野 司

  　研究概要を見る

  臨床データから得られた知見として、慢性脳虚血性疾患に対する開頭血行再建術で得られたくも膜と脳脊髄液を使用した。対象群として開頭による非虚血性疾患で得られた前頭葉皮質血管(M4)直上のくも膜を使用した。これまでの研究成果としては、くも膜の厚さは年齢や疾患が影響しており、厚いくも膜では内層に線維芽細胞やマクロファージが増勢し、VEGFαやTGFβなどの炎症マーカーが増加していた。また、くも膜内の線維化や慢性炎症が確認されていることを基に、免疫組織学的に線維化に関わる炎症マーカーや間葉系幹細胞の存在、血管新生の有無を確認した。虚血性疾患において、強い炎症反応が認められており、疾患による影響もみられることがわかった。 また、実験動物として両側総頸動脈閉塞による認知症モデルによる評価を行った。8週のWister kyotoラットにおいて、両側総頚動脈閉塞モデルを作成し、頚動脈閉塞後4週間目に実験用7.0TMRIで脳小血管病性変化を計測した。また、電気生理学的な影響を測定するため、Pinnacle Technology社の大脳皮質脳波測定システムで、てんかん波や高次脳機能を反映するβ波やγ波などの高周波帯域のパワースペクトラム解析を行った。虚血によるてんかん原生が非常に強く影響を及ぼしていることを見出すとともに、MRI及び電気生理学的な虚血の影響を推し量れるシステムを確立した。また、両側頚動脈閉塞と再灌流の電気生理学的変化や組織変化、MRI画像変化の違いを検討し、組織学的変化が及ぼす電気生理学的異常について検討中である。

• ヒト中枢神経系におけるGlymphatic systemの機能解明

  基盤研究(C)

  研究期間:

  2018年04月

  -

  2022年03月

   

  秋山 幸功, 鈴木 拓, 堀尾 嘉幸, 鰐渕 昌彦, 三上 毅, 三國 信啓

  　研究概要を見る

  MRSを用いて、正常ボランティアと正常圧水頭症患者において脳実質内NAA, macromoleculeの濃度を測定し、比較検討を行った。正常圧水頭症患者において有意にmacromoleculeの増加およびNAAの低下が認められ、何らかのclearance systemの障害が疾患に影響していることが判明した。

• 神経幹細胞と癌幹細胞の比較解析

  若手研究(B)

  研究期間:

  2009年

  -

  2011年

   

  秋山 幸功

  　研究概要を見る

  神経幹細胞と腫瘍幹細胞の比較実験において、腫瘍幹細胞の増殖力が神経幹細胞に対して、非常に弱いことが判明した。また、分離培養する際の条件も、神経幹細胞と同様のものでは、まわりの腫瘍細胞(非神経幹細胞)の影響と思われる、培養の困難性があることが判明した。腫瘍幹細胞に特異的と考えられているCD133陽性細胞の培養に成功し、その細胞がneuron系、glia系、oligodendroglia系の3系統に分化誘導することが可能であった。 CD133陽性細胞が長寿遺伝子として知られるSIRT1遺伝子を発現していることが判明した。今後、脳腫瘍幹細胞におけるSIRT1遺伝子の発現量の相違を検索することにより、その細胞内における動態について検討する。

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