2023/02/15 更新

写真a

ナカニシ カズキ
中西 和毅
NAKANISHI Kazuki
所属
医歯学域医学系 医学部 特任助教
職名
特任助教

学位

  • 博士(保健学) ( 2021年3月   鹿児島大学 )

 

論文

  • Otsuka S., Itashiki Y., Tani A., Matsuoka T., Takada S., Matsuzaki R., Nakanishi K., Norimatsu K., Tachibe Y., Kitazato R., Nojima N., Kakimoto S., Kikuchi K., Maruyama I., Sakakima H. .  Effects of different remote ischemia perconditioning methods on cerebral infarct volume and neurological impairment in rats .  Scientific Reports13 ( 1 ) 2158   2023年12月

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    記述言語:日本語   出版者・発行元:Scientific Reports  

    Remote ischemic perconditioning (RIPerC) is a novel neuroprotective method against cerebral infarction that has shown efficacy in animal studies but has not been consistently neuroprotective in clinical trials. We focused on the temporal regulation of ischemia–reperfusion by RIPerC to establish an optimal method for RIPerC. Rats were assigned to four groups: 10 min ischemia, 5 min reperfusion; 10 min ischemia, 10 min reperfusion; 5 min ischemia, 10 min reperfusion; and no RIPerC. RIPerC interventions were performed during ischemic stroke, which was induced by a 60-min left middle cerebral artery occlusion. Infarct volume, sensorimotor function, neurological deficits, and cellular expressions of brain-derived neurotrophic factor (BDNF), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), and caspase 3 were evaluated 48 h after the induction of ischemia. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) was also performed. RIPerC of 10 min ischemia/10 min reperfusion, and 5 min ischemia/10 min reperfusion decreased infarct volume, improved sensorimotor function, decreased Bax, caspase 3, and TUNEL-positive cells, and increased BDNF and Bcl-2 expressions. Our findings suggest RIPerC with a reperfusion time of approximately 10 min exerts its neuroprotective effects via an anti-apoptotic mechanism. This study provides important preliminary data to establish more effective RIPerC interventions.

    DOI: 10.1038/s41598-023-29475-2

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  • Tani A., Sakakima H., Otsuka S., Mizuno K., Nakanishi K., Norimatsu K., Takada S., Matsuoka T., Matsuzaki R., Nakakogawa T., Maruyama I. .  Stimulation of functional recovery via neurorepair mechanisms by the traditional Japanese Kampo medicine, Ninjin'yoeito, and physical exercise in a rat ischemic stroke model .  Journal of Ethnopharmacology302 ( Pt B ) 115927   2023年2月

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    記述言語:日本語   出版者・発行元:Journal of Ethnopharmacology  

    Ethnopharmacological relevance: Ninjin'yoeito (NYT), a traditional Japanese Kampo medicine consisting of 12 herbs, has been reported to improve cognitive dysfunction, depression, and neurological recovery in patients with neurovascular diseases such as Alzheimer's disease and stroke. Several studies have reported that the NYT components exert neurotrophic, neurogenic, and neuroprotective effects. In addition, exercise enhances neuroprotection and functional recovery after stroke. Rehabilitative exercises and pharmacological agents induce neurophysiological plasticity, leading to functional recovery in stroke patients. These reports indicate that NYT treatment and exercise may promote functional recovery following stroke through their beneficial effects. However, no study has determined the effects of NYT and the possible mechanisms of neurorepair and functional recovery after stroke. Aim of the study: This study aimed to investigate the combined effects of NYT and exercise on neuroprotection and functional recovery and the underlying mechanisms in a rat ischemic stroke model. Materials and methods: Stroke was induced with 60-min middle cerebral artery occlusion (MCAO) followed by reperfusion in adult male Sprague-Dawley rats. After stroke, the rats were assigned to four groups: ischemia reperfusion (IR), NYT, exercise (Ex), and NYT + Ex. NYT-treated rats were fed a diet containing 1% NYT one day after stroke. Exercise was performed using a motorized treadmill for 5 days a week (8–15 m/min, 20 min/day), starting 3 days after stroke. The NYT treatment and exercise were continued for 4 weeks after the stroke. Infarct volume, neurological deficits, sensorimotor functions, expression of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase A (TrkA) and B (TrkB), caspase-3 activity, and the p-Akt/Akt ratio were examined by immunohistochemistry and western blotting. Results: Compared to the IR group, all treated groups indicated reduced infarct volumes. The NYT + Ex group showed significantly improved waking time and beam walking score compared with the IR group. The expression of NGF/TrkA/p-TrkA and BDNF/TrkB was significantly increased in the NYT + Ex group compared with those in the IR group, whereas the number of caspase-3 positive cells around the lesion was significantly lower in the NYT + Ex group than in the IR group. In addition, the ratio of p-Akt/Akt was significantly higher in the NYT + Ex group than in the IR group. Conclusions: This study suggests that NYT in combination with exercise provides neuroprotective effects and improves sensorimotor function by stimulating NGF/TrkA and BDNF/TrkB, and by activating the Akt pathway in ischemic stroke of rats. NYT may be an effective adjunctive agent in post-stroke rehabilitation.

    DOI: 10.1016/j.jep.2022.115927

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  • 菊池 清志, 丸山 征郎, 田中 永一郎, 森岡 基浩, 中西 和毅 .  AMPK活性化内因性単糖 1、5-AFによるエクササイズ効果増強の検証 .  デサントスポーツ科学42   64 - 68   2022年6月

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    記述言語:日本語   出版者・発行元:(公財)石本記念デサントスポーツ科学振興財団  

    AMPK(AMP-activated protein kinase)活性化がフレイル予防に期待されている.老化促進モデルマウス(SAM8:Senescence Accelerated Mouse8)にて,AMPK活性化作用を有する自然食材由来の単糖による行動解析を中心とする評価をした.本単糖配合飼料摂取群,対照飼料摂取群に対して,飼育ケージ内にて自由飼育を行い,9ヵ月後にOpen Fieldを用いて,SMARTビデオ画像行動解析装置にて解析したが,両群間(n=12)で有意な差はみられなかった.今回の検証においては本単糖の有効性は実証できなかった.(著者抄録)

  • Takada S., Setoyama K., Norimatsu K., Otsuka S., Nakanishi K., Tani A., Nakakogawa T., Matsuzaki R., Matsuoka T., Sakakima H., Tancharoen S., Maruyama I., Tanaka E., Kikuchi K., Uchikado H. .  E8002 Reduces Adhesion Formation and Improves Joint Mobility in a Rat Model of Knee Arthrofibrosis .  International Journal of Molecular Sciences23 ( 3 )   2022年2月

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    記述言語:日本語   出版者・発行元:International Journal of Molecular Sciences  

    Knee arthrofibrosis is a common complication of knee surgery, caused by excessive scar tissue, which results in functional disability. However, no curative treatment has been established. E8002 is an anti-adhesion material that contains L-ascorbic acid, an antioxidant. We aimed to evaluate the efficacy of E8002 for the prevention of knee arthrofibrosis in a rat model, comprising injury to the surface of the femur and quadriceps muscle 1 cm proximal to the patella. Sixteen male, 8week-old Sprague Dawley rats were studied: in the Adhesion group, haemorrhagic injury was induced to the quadriceps and bone, and in the E8002 group, an adhesion-preventing film was implanted between the quadriceps and femur after injury. Six weeks following injury, the restriction of knee flexion owing to fibrotic scarring had not worsened in the E8002 group but had worsened in the Adhesion group. The area of fibrotic scarring was smaller in the E8002 group than in the Adhesion group (p < 0.05). In addition, the numbers of fibroblasts (p < 0.05) and myofibroblasts (p < 0.01) in the fibrotic scar were lower in the E8002 group. Thus, E8002 reduces myofibroblast proliferation and fibrotic scar formation and improves the range of motion of the joint in a model of knee injury.

    DOI: 10.3390/ijms23031239

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  • 角園 恵, 吉里 雄伸, 今井 孝樹, 中西 和毅, 谷 明, 松崎 凌真, 中小川 智美, 松岡 輝樹, 榊間 春利 .  神経因性疼痛のメカニズムと神経因性疼痛ラットモデルにおける運動療法の鎮痛効果 .  基礎理学療法学25 ( Supplement ) S8-1 - S8-1   2022年

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    記述言語:日本語   出版者・発行元:一般社団法人 日本基礎理学療法学会  

    DOI: 10.24780/jjptf.o-1-3-5

  • 松崎 凌真, 中小川 智美, 松岡 輝樹, 谷 明, 則松 貢輔, 中西 和毅, 髙田 聖也, 大塚 章太郎, 榊間 春利 .  緑茶カテキン摂取と運動療法の併用が老化促進マウス(SAMP8)の骨格筋に及ぼす影響 .  基礎理学療法学25 ( Supplement ) S70-1 - S70-1   2022年

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    記述言語:日本語   出版者・発行元:一般社団法人 日本基礎理学療法学会  

    DOI: 10.24780/jjptf.p-2-1-7

  • 則松 貢輔, 中西 和毅, 谷 明, 松崎 凌真, 中小川 智美, 松岡 輝樹, 大塚 章太郎, 高田 聖也, 角園 恵, 榊間 春利 .  老化促進マウスにおける低強度トレッドミル運動は加齢による変形性膝関節症の進行を緩和する .  基礎理学療法学25 ( Supplement ) S14-1 - S14-1   2022年

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    記述言語:日本語   出版者・発行元:一般社団法人 日本基礎理学療法学会  

    DOI: 10.24780/jjptf.o-1-6-2

  • Sumizono M., Yoshizato Y., Yamamoto R., Imai T., Tani A., Nakanishi K., Nakakogawa T., Matsuoka T., Matsuzaki R., Tanaka T., Sakakima H. .  Mechanisms of Neuropathic Pain and Pain-Relieving Effects of Exercise Therapy in a Rat Neuropathic Pain Model .  Journal of Pain Research15   1925 - 1938   2022年

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    記述言語:日本語   出版者・発行元:Journal of Pain Research  

    Purpose: Pain disrupts the daily and social lives of patients with neuropathic pain. Effective treatment of neuropathic pain is difficult. Pharmacological treatments for neuropathic pain are limited, and 40–60% of patients do not achieve even partial relief of their pain. This study created a chronic constriction injury (CCI) model in rats to examine the effects of regular exercise on neuropathic pain relief, elucidate the mechanism, and determine the effects of neuropathic pain in the hippocampus. Methods: CCI model rats were randomly divided into exercise (Ex) and no exercise (No-Ex) groups. Normal rats (Normal group) were used as controls. The Ex group exercised on a treadmill at 20 m/min for 30 min, 5 days per week for 5 weeks post-CCI. The 50% pain response threshold was assessed by mechanical stimulation. Using immunohistochemistry, we examined activation of glial cells (microglia and astrocytes) by CCR2 and TRAF6 expression in the spinal cord dorsal horn and DCX and PROX1 expression in the hippocampal dentate gyrus. Results: The 50% pain response threshold was significantly lower in the Ex than in the No-Ex group at 5 weeks post-CCI, indicating pain relief. In the spinal cord dorsal horn, IBA1, CCR2, and TRAF6 expression was markedly lower in the Ex group than in the No-Ex group at 3 weeks post-CCI. IBA1, GFAP, CCR2, and TRAF6 expression was markedly lower in the Ex group than in the No-Ex group at 5 weeks post-CCI. In the hippocampus, DCX, but not PROX1, expression was significantly higher in the Ex group than in the No-Ex group at 3 weeks post-CCI. At 5 weeks post-CCI, both DCX and PROX1 expression was markedly increased in the Ex group compared to the No-Ex group. Conclusion: Our findings suggest that regular exercise can improve the neuropathic pain-induced neurogenic dysfunction in the hippocampal dentate gyrus.

    DOI: 10.2147/JPR.S367818

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  • Otsuka S., Setoyama K., Takada S., Nakanishi K., Terashi T., Norimatsu K., Tani A., Sakakima H., Maruyama I., Tancharoen S., Tanaka E., Kikuchi K. .  Preconditioning Exercise in Rats Attenuates Early Brain Injury Resulting from Subarachnoid Hemorrhage by Reducing Oxidative Stress, Inflammation, and Neuronal Apoptosis .  Molecular Neurobiology58 ( 11 ) 5602 - 5617   2021年11月

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    記述言語:日本語   出版者・発行元:Molecular Neurobiology  

    Subarachnoid hemorrhage (SAH) is a catastrophic form of stroke responsible for significant morbidity and mortality. Oxidative stress, inflammation, and neuronal apoptosis are important in the pathogenesis of early brain injury (EBI) following SAH. Preconditioning exercise confers neuroprotective effects, mitigating EBI; however, the basis for such protection is unknown. We investigated the effects of preconditioning exercise on brain damage and sensorimotor function after SAH. Male rats were assigned to either a sham-operated (Sham) group, exercise (Ex) group, or no-exercise (No-Ex) group. After a 3-week exercise program, they underwent SAH by endovascular perforation. Consciousness level, neurological score, and sensorimotor function were studied. The expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), 4-hydroxynonenal (4HNE), nitrotyrosine (NT), ionized calcium-binding adaptor molecule 1 (Iba1), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1β (IL-1β), 14–3-3γ, p-β-catenin Ser37, Bax, and caspase-3 were evaluated by immunohistochemistry or western blotting. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling (TUNEL) assay was also performed. After SAH, the Ex group had significantly reduced neurological deficits, sensorimotor dysfunction, and consciousness disorder compared with the No-Ex group. Nrf2, HO-1, and 14–3-3γ were significantly higher in the Ex group, while 4HNE, NT, Iba1, TNF-α, IL-6, IL-1β, Bax, caspase-3, and TUNEL-positive cells were significantly lower. Our findings suggest that preconditioning exercise ameliorates EBI after SAH. The expression of 4HNE and NT was reduced by Nrf2/HO-1 pathway activation; additionally, both oxidative stress and inflammation were reduced. Furthermore, preconditioning exercise reduced apoptosis, likely via the 14–3-3γ/p-β-catenin Ser37/Bax/caspase-3 pathway.

    DOI: 10.1007/s12035-021-02506-7

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  • Otsuka S., Sakakima H., Tani A., Nakanishi K., Takada S., Norimatsu K., Maejima H., Maruyama I. .  Effects of detraining on preconditioning exercise-induced neuroprotective potential after ischemic stroke in rats .  Brain Structure and Function226 ( 7 ) 2169 - 2180   2021年9月

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    記述言語:日本語   出版者・発行元:Brain Structure and Function  

    Preconditioning exercise prior to stroke exerts neuroprotection, which is an endogenous strategy that leads the brain cells to express several intrinsic factors and inhibits their apoptosis. However, it is unclear how long these benefits last after exercise cessation. The aim of this study was to investigate the effects of detraining on preconditioning exercise-induced neuroprotective potential after stroke. Rats were trained using a treadmill for aerobic exercise 5 days each week for 3 weeks, and their neuroprotective effects were examined until 3 weeks after exercise cessation. Stroke was induced by 60 min of left middle cerebral artery occlusion at 3 days, 1, 2, and 3 weeks after exercise cessation. Infarct volume, neurological deficits, sensorimotor function, expression levels of brain-derived neurotrophic factor (BDNF), hypoxia-induced factor-1α (HIF-1α), glial fibrillary acidic protein (GFAP), and P2X7 receptors, and apoptosis activity were examined using immunohistochemical and western blot analyses. Preconditioning exercise significantly reduced infarct volume and ameliorated sensorimotor function after stroke, and its beneficial effects were observed until 2 weeks after exercise cessation. The expression level of BDNF in the ischemic brain was significantly upregulated at 3 days after exercise cessation; however, the expression levels of HIF-1α, GFAP, and P2X7 receptor were significantly increased until 2 weeks after exercise cessation; thereby, significant anti-apoptotic effects were lost at 3 weeks of detraining. Our findings suggest that preconditioning exercise-induced neuroprotective potential may be lost shortly after exercise cessation. Neuroprotection through intrinsic protective factors, such as BDNF and HIF-1α, may provide different neuroprotective mechanisms in a time-dependent manner during detraining.

    DOI: 10.1007/s00429-021-02317-5

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  • Nakanishi K., Sakakima H., Norimatsu K., Otsuka S., Takada S., Tani A., Kikuchi K. .  Effect of low-intensity motor balance and coordination exercise on cognitive functions, hippocampal Aβ deposition, neuronal loss, neuroinflammation, and oxidative stress in a mouse model of Alzheimer's disease .  Experimental Neurology337   113590   2021年3月

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    記述言語:日本語   出版者・発行元:Experimental Neurology  

    It is well known that physical exercise reduces the risk of Alzheimer's disease (AD) and age-related cognitive decline. However, its mechanisms are still not fully understood. This study aimed to investigate the effect of aging and rotarod exercise (Ex) on cognitive function and AD pathogenesis in the hippocampus using senescence-accelerated mice prone 8 (SAMP8). Cognitive functions clearly declined at 9-months of age. Amyloid-beta (Aβ) deposition, neuronal loss, and glia activation-induced neuroinflammation increased with aging. The rotarod Ex prevented the decline of cognitive functions corresponding to the suppression of Aβ deposition, neuroinflammation, neuronal loss, inducible nitric oxide synthase (NOS) activities, and neuronal NOS activities. In addition, the rotarod Ex suppressed proinflammatory M1 phenotype microglia and A1 phenotype astrocytes. Our findings suggest that low-intensity motor balance and coordination exercise prevented age-related cognitive decline in the early stage of AD progression, possibly through the suppression of hippocampal Aβ deposition, neuronal loss, oxidative stress, and neuroinflammation, including reduced M1 and A1 phenotypes microglia and astrocytes.

    DOI: 10.1016/j.expneurol.2020.113590

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  • 中島 悠輔, 足立 貴志, 橘木 康文, 中西 和毅, 榊間 春利, 井尻 幸成 .  投球動作中の肘関節の関連性について .  理学療法学Supplement48S1 ( 0 ) D-43 - D-43   2021年

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    記述言語:日本語   出版者・発行元:公益社団法人 日本理学療法士協会  

    DOI: 10.14900/cjpt.48s1.d-43

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講演・口頭発表等

  • 中島 悠輔, 足立 貴志, 橘木 康文, 中西 和毅, 榊間 春利, 井尻 幸成 .  投球動作中の肘関節の関連性について .  理学療法学  2021年12月  (一社)日本理学療法学会連合

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    記述言語:日本語  

  • 中小川 智美, 松崎 凌真, 松岡 輝樹, 則松 貢輔, 谷 明, 中西 和毅, 高田 聖也, 大塚 章太郎, 稲留 真輝, 柿本 翔吾, 加藤 夕貴, 立部 勇汰, 野島 菜央, 日高 優悟, 榊間 春利 .  運動と緑茶カテキン摂取が変形性膝関節症モデルマウスの疼痛発現や脊髄グリア細胞の活性化に及ぼす影響 .  形態・機能  2022年8月  コ・メディカル形態機能学会

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    記述言語:日本語  

  • Norimatsu Kosuke, Nakanishi Kazuki, Tani Akira, Fukumaru Keita, Otsuka Shotaro, Takada Seiya, Sakakima Harutoshi .  老化促進マウスモデル(SAMP8)の膝関節における加齢変化と運動の効果について(Effects of aging and balance exercise on the knee joint of the senescence accelerated mouse(SAMP8)) .  The Journal of Physiological Sciences  2021年8月  (一社)日本生理学会

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    記述言語:英語  

  • 則松 貢輔, 中西 和毅, 谷 明, 松岡 輝樹, 松崎 凌真, 中小川 智美, 大塚 章太郎, 高田 聖也, 榊間 春利 .  老化促進マウスにおける関節軟骨変性に及ぼす種々のメカニカルストレスの影響について .  形態・機能  2021年8月  コ・メディカル形態機能学会

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    記述言語:日本語  

  • 新留 卓弥, 善福 大輔, 井尻 幸成, 中西 和毅, 榊間 春利, 山浦 一郎 .  投球時に肘下がりを生じる中学野球投手の特徴 筋力と関節可動域の関係性 .  日本臨床スポーツ医学会誌  2021年10月  (一社)日本臨床スポーツ医学会

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    記述言語:日本語