若手道場

若手道場神経炎症

7月6日（木）　14:20-15:20　Room H 1W④-1 低温刺激はTRPV4を介してミクログリアの神経傷害的な活性化を抑制する Hypothermia attenuates neurotoxic microglial activation via TRPV4 channel 鳥内　皐暉¹, 福田　直哉¹, 垣田　博樹^1,2, 青木　啓将¹, 田村　哲也³, 竹下　覚^1,2, 山田　恭聖², 青山　峰芳¹ 1. 名古屋市立大学大学院　薬学研究科　病態解析学分野, 2. 愛知医科大学　周産期母子医療センター　新生児集中治療部門, 3. 名古屋市立大学　大学院医学研究科　麻酔科学・集中治療分野 Kohki Toriuchi¹, Naoya Fukuda¹, Hiroki Kakita^1,2, Hiromasa Aoki¹, Yetsuya Tamura³, Satoru Takeshita^1,2, Yasumasa Yamada², Mineyoshi Aoyama¹ 1. Department of Pathobiology, Nagoya City University Graduate School of Pharmaceutical Sciences, 2. Department of Perinatal and Neonatal Medicine, Aichi Medical University, 3. Department of Anesthesiology and Intensive Care Medicine, Nagoya City University Graduate school of Medical Sciences Therapeutic hypothermia (TH) provides neuroprotection, however, the cellular mechanisms underlying the neuroprotective effect of TH are not fully elucidated. Transient receptor potential vanilloid 4 (TRPV4), a non-selective cation channel, is activated by a temperature stimulus around 34°C. The relationship between TH and TRPV4 is suggested because the recommended body temperature for TH is 33.5°C. In the present study, we investigated whether hypothermia attenuates microglial activation via TRPV4 channel. After lipopolysaccharide (LPS) stimulation, microglia were cultured under normothermic (37°C) or hypothermic (33.5°C) conditions. Hypothermic culture suppressed the expression of proinflammatory cytokines and inducible nitric oxide synthase. In addition, phagocytosis of latex beads was significantly suppressed under hypothermic conditions. Furthermore, AMP-activated protein kinase (AMPK)-NF-κB signaling was inhibited under hypothermic conditions. TRPV4 antagonist treatment under normothermic culture mimicked the inhibitory effects of hypothermic culture on microglial activation. In contrast, TRPV4 agonist treatment under hypothermic culture counteracted the inhibitory effect of hypothermic culture. These results suggest that therapeutic hypothermia inhibits microglial activation via the TRPV4-AMPK-NF-κB pathway.		7月6日（木）　14:20-15:20　Room H 1W④-2 SEMA3Eを標的とした神経障害性疼痛の新規治療開発 Development of a novel neuropathic pain treatment targeting SEMA3E 吉富　小都¹, 藤井　敬之¹, 本田　裕之², 賀集　薫¹, 宮地　佑希野¹, 緒方　英紀¹, 山崎　亮¹, 岩城　徹², 磯部　紀子¹ 1. 九州大学大学院医学研究院　神経内科学, 2. 九州大学大学院医学研究院　神経病理学 Sato Yoshidomi¹, Takayuki Fujii¹, Hiroyuki Honda², Kaoru Kashu¹, Yukino Miyachi¹, Hidenori Ogata¹, Ryo Yamasaki¹, Toru Iwaki², Noriko Isobe¹ 1. Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, 2. Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan [Objective] Semaphorins (SEMAs) and their receptors, Plexins, are expressed in dorsal root ganglia (DRG). However, it remains unclear their association with neuropathic pain (NP). Herein, we aimed to clarify the association between NP and SEMA-Plexin pathway.[Methods] We quantified serum SEMA3A, 3E, 4A, 4D, and 7A in 45 patients with NP and 17 age- and sex-matched healthy controls (HCs) by enzyme-linked immunosorbent assay (ELISA). SEMA expression was assessed by immunohistochemistry (IHC) in DRG and peripheral nerve (PN) tissues of 4 autopsied NP patients and 3 controls as well as NP model mice with partial sciatic nerve ligation (PSL). Moreover, we intraperitoneally injected anti-SEMA blocking antibody or control IgG into NP model mice for 5 consecutive days after PSL, and assessed mechanical hypersensitivity by von Frey test on day 4 after PSL. [Results] Serum ELISA showed a significant increase of the SEMA3E in NP patients compared to HCs. IHC revealed enhanced SEMA3E expression in DRG and PN tissues of both NP patients and NP model mice, especially in macrophages. In vitro, SEMA3E treatment inhibited neurite outgrowth of mouse DRG neurons. Injection of anti-SEMA3E blocking antibody abolished DRG macrophage activation, promoted axon regeneration, and resolved hypersensitivity in NP model mice. [Conclusions] SEMA3E was associated with NP and could be a novel target for NP.

7月6日（木）　14:20-15:20　Room H 1W④-3 変形性膝関節症の有効な治療法である末梢神経パルス高周波法（PRF）の作用メカニズム解明 Elucidation of the mechanism of peripheral nerve Pulsed Radiofrequency, an effective treatment for knee osteoarthritis 弓場　智雄^1,2, 小山　佳久^2,3, 高橋　亜矢子¹, 藤野　裕士¹, 島田　昌一^2,3 1. 大阪大学医学部附属病院麻酔集中治療医学講座, 2. 大阪大学大学院医学系研究科神経細胞生物学, 3. 大阪精神医療センターこころの科学リサーチセンター依存症ユニット Tomoo Yuba^1,2, Yoshihisa Koyama^2,3, Ayako Takahashi¹, Yuji Fujino¹, Shoichi Shimada^2,3 1. Department of anesthesiology and intensive care, Osaka University graduate school of medicine We have reported the analgesic effect of Pulsed Radiofrequency (PRF) to the saphenous nerve in osteoarthritis (OA) patients with knee pain. Thus, PRF is an excellent treatment for OA, but the detailed mechanism is still unknown. Surprisingly, patients whose knee pain improved with PRF treatment also had alleviated joint swelling. Therefore, we hypothesized that the anti-inflammatory action of PRF contributed to the analgesic effect.To investigate anti-inflammation effect of PRF, we treated sciatic nerves of knee OA mouse model with PRF and performed a comparative analysis between the PRF-treated and untreated groups.In the PRF-treated group, knee synovitis was improved, and increased inflammatory cytokine expression in the knee joint was alleviated. Since the action site of PRF is the nerve, we investigated the involvement of dorsal root ganglion (DRG) neurons in its anti-inflammatory effects. Neural tracer and Western blot analysis showed that axonal transport was suppressed specifically in DRG small neurons and inflammatory factors (calcitonin gene-related peptide and substance P ) in the knee joint was significantly decreased in the PR-treated group.Our findings may provide a clue to the elucidation of the anti-inflammatory effects of PRFs, so we would like to discuss this research in this presentation.