Education 【 display / non-display 】

Education 【 display / non-display 】

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  1995

  Sapporo Medical University  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• M.D., Ph.D.

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

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  日本脳神経外科学会

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  The Japan Stroke Society

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  Japan Neurosurgical Society

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  Japanese Association for Acute Medicine

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  日本脊髄外科学会

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Neurosurgery  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   附属病院 脳神経外科学講座   講師  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 脳神経外科学

• 脳卒中

• 外傷

• 脊髄外科

• Neuroscience

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• 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  2023.06  [Domestic journal]

  　View Summary

  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

• 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  2023.06  [Domestic journal]

  　View Summary

  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

• 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  2023.06  [International journal]

  　View Summary

  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

• The intraoperative motor-evoked potential when propofol was changed to remimazolam during general anesthesia: a case series.

  Shoto Yamada, Yukinori Akiyama, Shunsuke Tachibana, Kengo Hayamizu, Yusuke Kimura, Shuichi Hashimoto, Michiaki Yamakage, Nobuhiro Mikuni

  Journal of anesthesia   37 ( 1 ) 154 - 159  2023.02  [Domestic journal]

  　View Summary

  Remimazolam is a short-acting benzodiazepine that was approved for clinical use in 2020. We report three patients who underwent surgery for cerebral and spinal cord tumors, in whom transcranial electrical stimulation-motor-evoked potential (TES-MEP) was successfully monitored under general anesthesia with remimazolam. During total intravenous anesthesia with propofol at a target concentration of 2.7 - 3.5 µg/mL and 0.1 - 0.35 µg/kg/min of remifentanil, delayed awakening, bradycardia, and hypotension during propofol anesthesia were expected in all three cases. With patient safety as the top priority, we considered changing the anesthetic agent. Propofol was replaced with remimazolam at a loading dose of 12 mg/kg/h for a few seconds (case 3), followed by 1 mg/kg/h for maintenance (cases 1-3). TES-MEP was recorded during propofol and remimazolam administration in all three patients. Amplitudes of TES-MEP during anesthesia with propofol and remimazolam were 461.5 ± 150 µV and 590.5 ± 100.9 µV, 1542 ± 127 µV and 1698 ± 211 µV, and 581.5 ± 91.3 µV and 634 ± 82.7 µV sequentially from Case 1. Our findings suggest that intraoperative TES-MEP could be measured when anesthesia was managed with remimazolam at 1 mg/kg/h.

  DOI PubMed

• Correction to: The intraoperative motor-evoked potential when propofol was changed to remimazolam during general anesthesia: a case series.

  Shoto Yamada, Yukinori Akiyama, Shunsuke Tachibana, Kengo Hayamizu, Yusuke Kimura, Shuichi Hashimoto, Michiaki Yamakage, Nobuhiro Mikuni

  Journal of anesthesia   37 ( 1 ) 160 - 160  2023.02  [Domestic journal]

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 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  2016.07

  Research paper, summary (international conference)  

• Primary clear cell carcinoma of the skull base and paranasal cavity: A case report

  Kengo Suzuki, Masahiko Wanibuchi, Yukinori Akiyama, Jun Ikeda, Yoshihiro Minamida, Tadashi Hasegawa, Kiyohiro Houkin, Nobuhiro Mikuni

  Neurological Surgery   40 ( 7 ) 617 - 621  2012.07

  　View Summary

  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  2005.10

  　View Summary

  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  2004.12

  　View Summary

  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  2004.04

  　View Summary

  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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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

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

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  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)

  Project Year :

  2021.04

  -

  2024.03

   

  秋山 幸功, 三上 毅, 三國 信啓, 石合 純夫

  　View Summary

  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)

  Project Year :

  2020.04

  -

  2023.03

   

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

  　View Summary

  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。

• Elucidation of the function of the Glymphatic system in the human central nervous system

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2018.04

  -

  2022.03

   

  AKIYAMA YUKINORI

  　View Summary

  Using MRS, the concentrations of NAA and macromolecules in brain parenchyma (White matter) were measured and compared in normal volunteers and patients with normal pressure hydrocephalus. The results showed that macromolecules were significantly increased and NAA was significantly decreased in patients with NPH, indicating that some kind of disturbance in the clearance system was affecting the disease.

• Comparison between neural and tumor stem cells

  Grant-in-Aid for Young Scientists (B)

  Project Year :

  2009

  -

  2011

   

  AKIYAMA Yukinori

  　View Summary

  In the comparison between neural and tumor stem cells, there was some differences such as a weakness of proliferation in the tumor stem cells. We succeeded to culture some cell lines of tumor stem cells from glioma patients. The tumor stem cells could differentiate into neuronal, glial and oligodendreoglial cell lineage which were demonstrated by immunocytochemistry. The circumference of the tumor cells which was non-tumor-stem cells might affect to proliferation of the tumor stem cells. The SIRT 1 gene known as a long life gene was appeared in the CD133 positive cells. The efficacy of the SIRT1 gene in the cells will be examined by retrieving the difference of the amount of the SIRT1 gene expression in the brain tumor stem cell in the future.

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