Language：Japanese   Publisher：一般社団法人 日本基礎理学療法学会  

DOI： 10.24780/jjptf.p-2-1-7

Language：English   Publishing type：Research paper (scientific journal)  

The gut microbiota has tremendous potential to affect the host's health, in part by synthesizing vitamins and generating nutrients from food that is otherwise indigestible by the host. 1,5-Anhydro-D-fructose (1,5-AF) is a monosaccharide with a wide range of bioactive potentials, including anti-oxidant, anti-inflammatory, and anti-microbial effects. Based on its potential benefits and minimal toxicity, it is anticipated that 1,5-AF will be used as a dietary supplement to support general health. However, the effects of 1,5-AF on the gut microbiota are yet to be clarified. Here, using an unbiased metagenomic approach, we profiled the bacterial taxa and functional genes in the caecal microbiota of mice fed a diet containing either 2% 1,5-AF or a reference sweetener. Supplementation with 1,5-AF altered the composition of the gut microbiota, enriching the proportion of Faecalibacterium prausnitzii. 1,5-AF also altered the metabolomic profile of the gut microbiota, enriching genes associated with nicotinamide adenine dinucleotide biosynthesis. These findings support the potential benefits of 1,5-AF, but further studies are required to clarify the impact of 1,5-AF on health and disease.

DOI： 10.1038/s41598-021-99052-y

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Mitochondrial functional abnormalities or quantitative decreases are considered to be one of the most plausible pathogenic mechanisms of Parkinson's disease (PD). Thus, mitochondrial complex inhibitors are often used for the development of experimental PD. In this study, we used rotenone to create in vitro cell models of PD, then used these models to investigate the effects of 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide with protective effects against a range of cytotoxic substances. Subsequently, we investigated the possible mechanisms of these protective effects in PC12 cells. The protection of 1,5-AF against rotenone-induced cytotoxicity was confirmed by increased cell viability and longer dendritic lengths in PC12 and primary neuronal cells. Furthermore, in rotenone-treated PC12 cells, 1,5-AF upregulated peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) expression and enhanced its deacetylation, while increasing AMP-activated protein kinase (AMPK) phosphorylation. 1,5-AF treatment also increased mitochondrial activity in these cells. Moreover, PGC-1α silencing inhibited the cytoprotective and mitochondrial biogenic effects of 1,5-AF in PC12 cells. Therefore, 1,5-AF may activate PGC-1α through AMPK activation, thus leading to mitochondrial biogenic and cytoprotective effects. Together, our results suggest that 1,5-AF has therapeutic potential for development as a treatment for PD.

DOI： 10.3390/ijms22189941

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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：Japanese   Publisher：コ・メディカル形態機能学会  

Language：Japanese   Publisher：IEEE Transactions on Applied Superconductivity  

As a high-temperature superconducting (HTS) conductor with a large current capacity applicable to a nuclear fusion experimental device, REBCO (REBa2CuOy) tapes and high-purity aluminum sheets are alternately laminated, placed in a groove of an aluminum alloy jacket having a circular cross section, and the lid is friction-stir welded. To make the current distribution and mechanical characteristics uniform, the conductor is twisted at the end of the manufacturing process. In the early prototype conductor, when the Ic was measured in liquid nitrogen under self-magnetic field conditions, Ic degradations were observed from the beginning, and the characteristic difference between the two prototype samples under the same manufacturing conditions were large. Furthermore, Ic degradation was progressed by repeating the thermal cycle from room temperature to liquid nitrogen temperature. This Ic degradation did not occur uniformly in the longitudinal direction of the conductor but was caused by local Ic degradation occurring at multiple locations. If the conductor was not manufactured uniformly in the longitudinal direction, the difference in thermal shrinkage between the REBCO tape and the aluminum alloy jacket caused local stress concentration in the REBCO tape and buckling occurred. Element experiments to explain this mechanism were conducted to clarify the conditions under which Ic degradation due to buckling occurs. Then prototype conductors were tested with improved manufacturing methods, and as a result, Ic degradation could be suppressed to 20% or less. We have achieved the prospect of producing a conductor with uniform characteristics in the longitudinal direction.

DOI： 10.1109/TASC.2021.3069923

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Language：English   Publishing type：Research paper (scientific journal)  

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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Language：English   Publishing type：Doctoral thesis  

BACKGROUND: Midkine (MK) is a multifunctional cytokine found upregulated in the brain in the presence of different disorders characterized by neuroinflammation, including neurodegenerative disorders and ischemia. The neuroinflammatory response to traumatic brain injury (TBI) represents a key secondary injury factor that can result in further neuronal injury. In the present study, we investigated the role of endogenous MK in secondary injury, including neuroinflammation, immune response, and neuronal apoptosis activity, after TBI. METHODS: Wild type (Mdk+/+) and MK gene deficient (Mdk-/-) mice were subjected to fluid percussion injury for TBI models and compared at 3, 7, and 14 days after TBI, in terms of the following: brain tissue loss, neurological deficits, microglia response, astrocytosis, expression of proinflammatory M1 and anti-inflammatory M2 microglia/macrophage phenotype markers, and apoptotic activity. RESULTS: As opposed to Mdk+/+ mice, Mdk-/- mice reported a significantly reduced area of brain tissue loss and an improvement in their neurological deficits. The ratios of the Iba1-immunoreactive microglia/macrophages in the perilesional site were significantly decreased in Mdk-/- than in the Mdk+/+ mice at 3 days after TBI. However, the ratios of the glial fibrillary acidic protein immunoreactive area were similar between the two groups. The M1 phenotype marker (CD16/32) immunoreactive areas were significantly reduced in Mdk-/- than in the Mdk+/+ mice. Likewise, the mRNA levels of the M1 phenotype markers (TNF-α, CD11b) were significantly decreased in Mdk-/- mice than in Mdk+/+ mice. Furthermore, flow cytometry analysis identified the M2 markers, i.e., CD163+ macrophages cells and arginase-1+ microglia cells, to be significantly higher in Mdk-/- than in Mdk+/+ mice. Finally, the ratios of apoptotic neurons were significantly decreased in the area surrounding the lesion in Mdk-/- than in Mdk+/+ mice following TBI. CONCLUSION: Our findings suggest that MK-deficiency reduced tissue infiltration of microglia/macrophages and altered their polarization status thereby reducing neuroinflammation, neuronal apoptosis, and tissue loss and improving neurological outcomes after TBI. Therefore, targeting MK to modulate neuroinflammation may represent a potential therapeutic strategy for TBI management.

DOI： 10.1186/s12974-020-1709-8

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Publisher：International Journal of Environmental Research and Public Health  

DOI： 10.3390/ijerph17155337

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Publisher：International Journal of Molecular Sciences  

DOI： 10.3390/ijms21113972

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PubMed

OBJECTIVE: Preconditioning exercise can exert neuroprotective effects after stroke; however, the effects of exercise intensity, frequency, duration are unknown. We investigated the neuroprotective effect of different frequency preconditioning exercise on neuronal apoptosis after cerebral ischemia in rats. METHODS: Rats were divided into the following five groups: 5 times a week of exercise (5/w-Ex) group, 3 times a week of exercise (3/w-Ex) group, once a week of exercise (1/w-Ex) group, no exercise (No-Ex) group, and intact control (control) group. Rats were made to run on a treadmill for 30 min per day at a speed of 25 m/min for 3 weeks. After the running program, the rats were subjected to 60-min left middle cerebral artery occlusion. Two days after ischemia, the cerebral infarct volume, neurological and motor function, Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, expression of caspase-3, and TUNEL positive cells were examined in the cerebral cortex surrounding the ischemic zone. RESULTS: The 3/w-Ex and 5/w-Ex groups showed significantly reduced infarct volumes compared with the No-Ex group, but the 1/w-Ex group did not. In addition, the 3/w-Ex and 5/w-Ex groups had improved neurological scores and sensorimotor function compared with the No-Ex group. The Bax/Bcl-2 ratio, expression of caspase-3, and TUNEL-positive cells significantly decreased in the penumbra area in the 3/w-Ex or 5/w-Ex groups compared with the No-Ex group. DISCUSSION: Our findings suggested that three times or more per week of high-intensity preconditioning exercise exert neuroprotective effects through the downregulation of the Bax/Bcl-2 ratio and caspase-3 activation after stroke. ABBREVIATIONS: TUNEL: terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick and labeling; MCAO:middle cerebral artery occlusion; BAX:Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; TTC: 2,3,5-triphenyltetrazorlium chloride.

DOI： 10.1080/01616412.2019.1580458

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In the original publication of the article, both the Fig. 2e and Fig. 7e have been published incorrectly and the correct figures are given below.

DOI： 10.1007/s00429-018-1815-x

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PubMed

14-3-3γ is an important early ischemia-inducible protective factor against ischemic cell death in cerebral cortical neurons. We investigated the anti-apoptosis mechanism of enhanced 14-3-3γ mediated by preconditioning exercise-induced brain ischemic tolerance after stroke. Rats were assigned to four groups: exercise and ischemia (Ex group), ischemia and no exercise (No-Ex group), exercise and no ischemia (Ex-only group), and no exercise and ischemia (control group). Rats were trained on a treadmill for 5 days a week for 3 weeks (running speed, 25 m/min; running duration, 30 min/day). After the exercise program, stroke was induced by left middle cerebral artery occlusion. The infarct volume, neurological deficits, and motor function, as well as expression levels of hypoxia-induced factor-1α (HIF-1α), 14-3-3γ, P2X7 receptors, p-β-catenin Ser37, Bax, and caspase 3 were evaluated by immunohistochemistry and western blotting. The expression of HIF-1α and 14-3-3γ significantly increased in neurons and astrocytes in the Ex-only group. HIF-1α was co-expressed with P2X7 receptor- and GFAP-positive astrocytes. After stroke, the Ex group had significantly reduced brain infarction. HIF-1α and 14-3-3γ significantly increased in the Ex group compared to the No-Ex group. In addition, p-β-catenin Ser37 significantly increased following elevated 14-3-3γ; in contrast, Bax and caspase 3 were significantly reduced in the Ex group. Our findings suggest that preconditioning exercise prior to ischemia induces neuron- and astrocyte-mediated brain ischemic tolerance through increased expression of HIF-1α and 14-3-3γ, which are intrinsic protective factors; the upregulated 14-3-3γ induced by preconditioning exercise reduces ischemic neuronal cell death through the 14-3-3γ/p-β-catenin Ser37/Bax/caspase 3 anti-apoptotic pathway.

DOI： 10.1007/s00429-018-1800-4

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PubMed

Publisher：Co-medical Research Society of Structure and Function  

<p>The contraction of deep abdominal musculature increase the stiffness of lumbar spine via the thoracolumbar fascia, and has also been shown to increase intra-abdominal pressure, which has important roles to provide stability of posture and lumbar spine. We investigated age-related changes of lateral abdominal muscles, and postoperative changes of these during rest position, abdominal drawing-in maneuver (Draw-in) and head-lift exercise by using ultrasound imaging device. Thirty elderly men with spine disorder to undergo surgery (elderly patients: average 67 years old) and 10 healthy young men (young men: average 22 years old) as a control group were participated in this study. The thickness and echo intensity of transversus abdominis (TrA), internal oblique (IO) and external oblique (EO) were observed. The elderly patients were measured at before surgery, at 2 and 7 days after surgery. No age-related change was observed in the TrA muscle thickness at rest position, but the EO muscle thickness in elderly patients reduced 50 % compared with those in young men (p<0.05). In the elderly patients, the amount of adipose tissue and non-contractile tissue was increasing, which was observed at superficial abdominal muscles rather than deep abdominal muscles. Compared with before operation, the TrA muscle at rest position was significantly reduced by 17% at 7 days after surgery (p<0.05). The muscle thickness of the TrA and IO were increased by the Draw-in and head-lift after surgery (p<0.05). Our findings indicate that age-related qualitative and quantitative changes were observed in superficial abdominal muscles compared with deep abdominal muscles, and the Draw-in and head-lift were effective trainings of activation deep abdominal muscles rather than superficial. In addition, our results suggest that the TrA might be atrophy in elderly individuals after lumbar surgery in the early phase because of operative stress or reduced activity by postoperative bed rest.</p>

DOI： 10.11172/keitaikinou.18.2

Publisher：公益社団法人 日本理学療法士協会  

<p>【はじめに、目的】細胞内には内在性保護因子が存在し、それらは脳虚血などの病態から細胞を保護するために活性化される。また、運動は、脳梗塞後に神経保護効果をもたらすことが報告され、そのメカニズムには内因性保護因子の活性化が関与している。本研究では、そのような内因性保護因子の中から転写因子の一つであるHIF-1α、内因性保護タンパクである14-3-3γに着目し、定期的な運動介入による脳虚血耐性の獲得と脳梗塞後の神経保護メカニズムについて調べた。</p><p>【方法】7週齢の雄性SDラット26匹を用い、3週間のトレッドミル運動群 (Ex-only群、n=6)、運動後に脳梗塞を作製する群(Ex群、n=7)、運動介入せず脳梗塞を作製する群(No-Ex群、n=7)、正常対照群(Control群、n=6)、の4群に分類した。トレッドミル運動は25m/minで30分/日、週5回行った。No-Ex群とControl群はゲージ内で3週間自由飼育した。運動終了後に60分間の虚血と再灌流障害により脳梗塞を作製し、脳梗塞作製48時間後に神経学的所見や運動機能評価を行い、脳を採取した。脳梗塞巣の体積、HIF-1α、14-3-3γ、活性化アストロサイトのマーカーであるGFAP、神経細胞のマーカーであるNeuN、アポトーシスに関与するBax、Caspase 3の発現を免疫組織化学染色及びWestern blotting法を用いて調べた。</p><p>【結果】定期的な運動介入による脳内変化に関して、Ex-only群のHIF-1αと14-3-3γの発現が有意に増加し(ｐ<0.05)、神経細胞やアストロサイト上で発現が観察された。脳梗塞作成後には、Ex群の脳梗塞巣の体積がNo-Ex群と比べて有意に小さく(p<0.05)、運動機能は有意に改善していた(p<0.05)。脳梗塞発症後には、No-Ex群に比べ、Ex群で14-3-3γの発現量が有意に増加し(p<0.05)、Bax、Caspase 3の発現は有意に減少していた(p<0.05)。</p><p>【考察】3週間の運動介入を行うことで内因性保護因子であるHIF-1α、14-3-3γの発現を誘導することが明らかとなり、虚血応答に対するこれらの因子が増加することは、運動によって脳虚血耐性が獲得出来たことを示唆している。我々の先行研究では予防的な運度介入は脳梗塞後の血管新生促進、グリア細胞の増殖促進、神経栄養因子の発現増加が生じることを報告しており、今回の運動群における脳梗塞後の神経保護メカニズムにはHIF-1αの発現に伴う14-3-3γ発現増加、血管新生促進、神経栄養因子の発現増加、14-3-3γのBax制御によるポトーシス抑制が関与していることが示唆された。</p><p>【結論】我々の研究は、予防理学療法の視点から運動による脳虚血耐性の獲得と脳梗塞後の神経保護効果とそのメカニズムを明らかにした。</p><p>【倫理的配慮，説明と同意】本研究は鹿児島大学動物実験委員会の承認を得て実施した。</p>

DOI： 10.14900/cjpt.46S1.I-56_1

Publisher：公益社団法人 日本理学療法士協会 九州ブロック会  

<p>【目的】</p><p>加齢に伴う腰椎変性疾患患者の腹部体幹筋の量的・質的変化に関する報告は少ない。本研究は超音波診断（エコー）装置を用いて、脊椎変性疾患を伴った中高齢者の安静、Draw-in、頭部挙上による側腹筋の筋厚や筋輝度を若年者と比較し、加齢による影響を調べた。さらに、腰椎手術前、術後早期の側腹筋の筋厚変化と術後早期のDraw-in、頭部挙上による腹部深層筋の筋厚を測定し、手術侵襲が腹部体幹筋に及ぼす影響を調べた。</p><p>【方法】</p><p>中高齢期の男性腰椎変性疾患患者13名（腰椎患者：平均年齢：67歳）と健常若年男性10名（若年者：平均年齢22歳）を対象とした。エコー装置（東芝社製、NEMIO SSA-550A）を用いて安静時、Draw-in、頭部挙上時にそれぞれ腹横筋、内・外腹斜筋の筋厚を計測した。腰椎患者は手術前日（術前）、術後2日、術後7</p><p>日に計測を行った。測定姿位は仰臥位とし、プローブの位置は左前腋窩線と臍部水平線の交点になるようにした。また、計測前に健常成人4名を対象として、検者内信頼性を検討し高い信頼性が得られた。統計学的検定にはWilcoxonの符号順位検定、フリードマン検定を行い、有意水準は5％とした。</p><p>【結果】</p><p>腰椎患者と若年者の腹横筋筋厚に大きな変化は認められなかったが、安静時外腹斜筋は腰椎患者で約51％有意に低下していた（p＝0.0001）。中高齢期の腰椎患者は若年者と比較して脂肪組織や非収縮性組織が増加しており、その傾向は深層筋より表層筋に著明であった。術前・術後の変化では、安静時腹横筋の筋厚は術前と比較して術後7日で約17％有意に低下していた（p＝0.012）。術後のDraw-in、頭部挙上により腹横筋、内腹斜筋の筋厚は増加したが、術前と比較して各運動課題による腹横筋筋厚の増加量は減少していた。</p><p>【考察】</p><p>加齢による変化と類似して中高齢期の腰椎患者は腹部表層筋になるほど筋厚減少や筋輝度変化が著明であった。Belavý（2017）らは若年者を対象とした安静臥床実験において、腹横筋の筋厚減少が早期から生じることを報告している。腹部深層筋は安静の影響を受けやすく、今回、腰椎患者は背部筋への手術侵襲や術後早期の活動低下が原因となり腹横筋の筋厚減少を生じたと考えられた。腰椎術後早期において、Draw-in や頭部挙上は表層筋より深層筋を活性化させた。これは起居動作獲得に向けた準備運動として、術後早期から深層筋を賦活化する運動が実行可能であることを示唆している。今後症例数を増やし腰椎疾患の特徴を明かにしていきたい。</p><p>【まとめ】</p><p>本研究は、側腹筋の加齢変化が深層筋より表層筋に顕著であり、Draw-in や頭部挙上は表層筋より深層筋を活性化させることを示した。また、腰椎術後患者は手術侵襲や安静による活動量の低下により術後早期に腹横筋の萎縮を生じる可能性があることを示唆した。</p><p>【倫理的配慮，説明と同意】</p><p>本研究は所属施設の倫理審査委員会の承認を得て実施した。実施に際し、被験者に対して口頭にて研究趣旨を十分説明し同意を得た上で実施した。開示すべき利益相反はない。</p>

DOI： 10.32298/kyushupt.2019.0_13

Publisher：公益社団法人 日本理学療法士協会  

<p>【はじめに、目的】</p><p>腰椎変性すべり症は，加齢による退行変性の代表的な疾患である。また、椎間関節水腫(facet effusion:FE)は腰椎変性すべりの生じている椎間関節裂隙部にT2強調画像で高輝度の変化を示す。本研究の目的はすべり症患者のFEの存在率やすべり椎間以外のFEの有無を調査し、さらに、FEと椎体周囲筋の断面積測定を行う。そして、腰部疾患を有さない高齢者との比較やすべりの程度での比較、すべりの程度、FE、筋断面積の関連性の検討を行うことである。</p><p>【方法】</p><p>腰椎変性すべり症と診断されたL4/5変性すべり症患者36名（すべり症群：男性7名、女性29名、66.3±8.8歳）を対象とした。また、腰椎疾患を有さない高齢者10名（男性4名、女性6名、63.8±11.3歳）を対照群とした。側方X線画像、MRI画像正中矢状断面像を用いて、Meyerding分類によるL4/5すべりの程度とTaillard法によるL4/5椎体すべり率を計測した。さらに、L4/5椎体の不安定性の評価としてX線（立位）とMRI（臥位）におけるすべり率の差を算出し、3%を基準に椎体不安定性を評価した。L3/4、L4/5、L5/S1におけるFEの有無や面積を測定した。さらに、L4下部レベルの大腰筋と脊柱起立筋の筋断面積を測定した。また、脂肪を含めた非収縮性組織（筋内の高輝度に表出されている部分）を測定し、筋断面積から非収縮性組織の差として除脂肪面積を算出した。さらに、脂肪面積と除脂肪面積から脂肪率を算出した。FEや筋断面積の計測にはMRIのT2強調画像を用いた。臨床症状としてL4/5すべり症患者の25名の痛みの程度（VAS）をカルテより収集した。統計処理は各群の正規性検定を行い、その後の統計学的検定を選択し検討した。有意水準は5%とし、統計処理ソフトは、SPSS(Version20, IBM, USA)を使用した。</p><p>【結果】</p><p>FEはすべり症群の100%、対照群の90%に観察された。対照群のFE面積はすべり症群と比較してL4/5椎体間で有意に小さかった（p<0.01）。Meyerding分類1°群や椎体不安定性3%以上群のFE面積は対照群と比較して有意に大きかった。すべり症群のすべり率や痛みの程度が大腰筋面積と有意な負の相関関係を認めた(r=-0.40、r=-0.41、p<0.05）。また、すべり率と脊柱起立筋の脂肪率に有意な正の相関を認めた(r=0.42、p<0.01)</p><p>【結論（考察も含む）】</p><p>L4/5すべり症群だけでなく対照群においてもFEが観察され、FEは椎間不安定性だけでなく椎体や椎間関節の加齢変化により生じる可能性が示唆された。L4/5すべり症患者では近接する椎体関節にもFEが観察され、椎間不安定性はFEの大きさに影響することが示唆された。椎体のすべり率や疼痛は大腰筋と関係があり、姿勢変化との関係が示唆された。すべり率と脊柱起立筋の脂肪率に正の相関があり、脊柱起立筋内の質的変化とすべりの程度に関係があることが示唆された。</p><p>【倫理的配慮，説明と同意】</p><p>本研究は霧島整形外科倫理審査委員会の承認（承認番号：00006）を得て行った。</p>

DOI： 10.14900/cjpt.46S1.H2-7_2

Uric acid (UA) therapy may prevent early ischemic worsening after acute stroke in thrombolysis patients. The aim of this study was to examine the influence of UA on the thrombolytic efficacy of alteplase in human blood samples by measuring thrombolysis under flow conditions using a newly developed microchip-based flow-chamber assay. Human blood samples from healthy volunteers were exposed to UA, alteplase, or a combination of UA and alteplase. Whole blood and platelet-rich plasma were perfused over a collagen- and thromboplastin-coated microchip, and capillary occlusion was monitored with a video microscope and flow-pressure sensor. The area under the curve (extent of thrombogenesis or thrombolysis) at 30 minutes was 92% lower in the UA-alteplase-treated group compared with the alteplase-treated group. D-dimers were measured to evaluate these effects in human platelet-poor plasma samples. Although hydrogen peroxide significantly decreased the elevation of D-dimers by alteplase, UA significantly inhibited the effect of hydrogen peroxide. Meanwhile, rat models of thromboembolic cerebral ischemia were treated with either alteplase or UA-alteplase combination therapy. Compared with alteplase alone, the combination therapy reduced the infarct volume and inhibited haemorrhagic transformation. UA enhances alteplase-mediated thrombolysis, potentially by preventing oxidative stress, which inhibits fibrinolysis by alteplase in thrombi.

DOI： 10.1038/s41598-018-34220-1

Scopus

PubMed

Neuropathic pain after spinal surgery, so-called failed back surgery syndrome, is a frequently observed common complication. One cause of the pain is scar tissue formation, observed as post-surgical epidural adhesions. These adhesions may compress surrounding spinal nerves, resulting in pain, even after successful spinal surgery. E8002 is an anti-adhesive membrane. In Japan, a clinical trial of E8002 is currently ongoing in patients undergoing abdominal surgery. However, animal experiments have not been performed for E8002 in spinal surgery. We assessed the anti-adhesive effect of E8002 in a rat laminectomy model. The dura matter was covered with an E8002 membrane or left uncovered as a control. Neurological evaluations and histopathological findings were compared at six weeks postoperatively. Histopathological analyses were performed by hematoxylin⁻eosin and aldehyde fuchsin-Masson Goldner staining. Three assessment areas were selected at the middle and margins of the laminectomy sites, and the numbers of fibroblasts and inflammatory cells were counted. Blinded histopathological evaluation revealed that adhesions and scar formation were reduced in the E8002 group compared with the control group. The E8002 group had significantly lower numbers of fibroblasts and inflammatory cells than the control group. The present results indicate that E8002 can prevent epidural scar adhesions after laminectomy.

DOI： 10.3390/ijms19051513

Scopus

PubMed

Background: Exercise regimens are established methods that can relieve neuropathic pain. However, the relationship between frequency and intensity of exercise and multiple cellular responses of exercise-induced alleviation of neuropathic pain is still unclear. We examined the influence of exercise frequency on neuropathic pain and the intracellular responses in a sciatic nerve chronic constriction injury (CCI) model. Materials and methods: Rats were assigned to four groups as follows: CCI and high-frequency exercise (HFE group), CCI and low-frequency exercise (LFE group), CCI and no exercise (No-Ex group), and naive animals (control group). Rats ran on a treadmill, at a speed of 20 m/min, for 30 min, for 5 (HFE) or 3 (LFE) days a week, for a total of 5 weeks. The 50% withdrawal threshold was evaluated for mechanical sensitivity. The activation of glial cells (microglia and astrocytes), expression of brain-derived neurotrophic factor (BDNF) and μ-opioid receptor in the spinal dorsal horn and endogenous opioid in the midbrain were examined using immunohistochemistry. Opioid receptor antagonists (naloxone) were administered using intraperitoneal injection. Results: The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn. In the No-Ex group, neuropathic pain showed the highest level of mechanical hypersensitivity at 2 weeks, which improved slightly until 5 weeks after CCI. In both exercise groups, the alleviation of neuropathic pain was accelerated through the regulation of glial activation, BDNF expression, and the endogenous opioid system. The expression of BDNF and endogenous opioid in relation to exercise-induced alleviation of neuropathic pain differed in the HFE and LFE groups. The effects of exercise-induced alleviation of mechanical hypersensitivity were reversed by the administration of naloxone. Conclusion: The LFE and HFE program reduced neuropathic pain. Our findings indicated that aerobic exercise-induced alleviated neuropathic pain through the regulation of glial cell activation, expression of BDNF in the ipsilateral spinal dorsal horn, and the endogenous opioid system.

DOI： 10.2147/JPR.S156326

Scopus

PubMed

Publisher：公益社団法人 日本理学療法士協会  

<p>【はじめに，目的】</p><p></p><p>神経因性疼痛に対する運動負荷は疼痛過敏を緩和することが報告されているが，その疼痛緩和メカニズムに関しては不明な点も多い。今回，絞扼性神経損傷（Chronic Constriction injury：CCI）モデルを用いて1週，3週，5週後の脊髄後角におけるグリア細胞やopioid受容体の変化，opioid受容体の拮抗薬投与による疼痛変化を調べた。</p><p></p><p>【方法】</p><p></p><p>7週齢の雄性SDラットを運動群，非運動群，正常対照群（n=3）に分けた。右坐骨神経の結紮によりCCIモデルを作製し，速度20m/min，30分間，5日/週，5週間運動を行った。術前，CCI後1週，2週，3週，4週，5週にVon Frey Testを実施し，50%疼痛閾値を算出した。CCI後1週（運動群n=3，非運動群n=4），3週（運動群n=4，非運動群n=6），5週（運動群n=6，非運動群n=5）に腰膨大部と中脳を採取して免疫組織学的観察を行った。腰膨大部を抗Iba1抗体，抗GFAP抗体，抗μ-opioid受容体抗体で染色した。中脳水道灰白質は抗β-endorphin/met-enkephalin抗体で染色した。染色切片より陽性細胞面積を定量化した。3週と5週後に生理食塩水に溶解したNaloxone（10mg/kg）を運動群のラットの腹腔内に投与し，投与前，投与後1，2，3，4時間後に疼痛域値の変化を調べた（n=6）。統計学的検定には，SPSSを使用し一元配置または二元配置分散分析後，多重比較検定を実施し，有意水準は5％とした。</p><p></p><p>【結果】</p><p></p><p>CCI後1週で両群とも疼痛が最大となった。4週，5週には運動群の疼痛閾値は非運動群と比較して有意に改善を認めた。CCI後1週において，損傷側腰髄後角のIba1陽性細胞は両群ともに非損傷側と比較して有意に増加していた。非運動群のGFAP陽性細胞は損傷側と非損傷側において大きな違いは見られなかったが，運動群のGFAP陽性細胞は損傷側で増加していた。μ-opioid受容体陽性細胞は脊髄後角の第I層に限局して観察されたが，損傷側と非損傷側で明らかな染色性の違いは観察されなかった。3週，5週後には運動群のIba1とGFAP陽性面積は非運動群と比較して減少していた。運動群の中脳水道灰白質におけるβ-endorphin/met-enkephalin陽性細胞面積は非運動群と比べて有意に増加していた。Naloxone投与により運動群の疼痛域値の低下を認め，4時間後には投与前の値に回復した。</p><p></p><p>【結論】</p><p></p><p>運動による疼痛緩和のメカニズムとして内因性オピオイドシステムの活性化が知られている。動物実験では十分な強度と期間の運動は中枢と末梢のβ-endorphinの放出を生じ，疼痛軽減に関与していることが報告されている。今回の結果は，疼痛の発現や維持には脊髄後角におけるミクログリアやアストロサイトの活性化が関与しており，運動による疼痛緩和には脊髄後角でのグリア細胞の活性化抑制が影響していることを示した。Naloxone投与により疼痛が再燃したことより，運動による中脳水道灰白質における内因性オピオイドの増加がopioid受容体を介して疼痛緩和に作用していることが示唆された。</p>

DOI： 10.14900/cjpt.2016.0630

Publisher：コ・メディカル形態機能学会  

Publisher：(公社)日本理学療法士協会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：(公社)日本理学療法士協会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：コ・メディカル形態機能学会  

Publisher：(公社)日本理学療法士協会