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Your search keyword '"Horiuchi, Hiroshi"' showing total 300 results
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300 results on '"Horiuchi, Hiroshi"'

21. Microglia sense astrocyte dysfunction and prevent disease progression in an Alexander disease model.

Author

Saito, Kozo, Shigetomi, Eiji, Shinozaki, Youichi, Kobayashi, Kenji, Parajuli, Bijay, Kubota, Yuto, Sakai, Kent, Miyakawa, Miho, Horiuchi, Hiroshi, Nabekura, Junichi, and Koizumi, Schuichi

Subjects
DISEASE progression, MICROGLIA, MEDICAL model, GENE expression, RNA sequencing
Abstract

Alexander disease (AxD) is an intractable neurodegenerative disorder caused by GFAP mutations. It is a primary astrocyte disease with a pathological hallmark of Rosenthal fibres within astrocytes. AxD astrocytes show several abnormal phenotypes. Our previous study showed that AxD astrocytes in model mice exhibit aberrant Ca2+ signals that induce AxD aetiology. Here, we show that microglia have unique phenotypes with morphological and functional alterations, which are related to the pathogenesis of AxD. Immunohistochemical studies of 60TM mice (AxD model) showed that AxD microglia exhibited highly ramified morphology. Functional changes in microglia were assessed by Ca2+ imaging using hippocampal brain slices from Iba1-GCaMP6-60TM mice and two-photon microscopy. We found that AxD microglia showed aberrant Ca2+ signals, with high frequency Ca2+ signals in both the processes and cell bodies. These microglial Ca2+ signals were inhibited by pharmacological blockade or genetic knockdown of P2Y12 receptors but not by tetrodotoxin, indicating that these signals are independent of neuronal activity but dependent on extracellular ATP from non-neuronal cells. Our single-cell RNA sequencing data showed that the expression level of Entpd2 , an astrocyte-specific gene encoding the ATP-degrading enzyme NTPDase2, was lower in AxD astrocytes than in wild-type astrocytes. In situ ATP imaging using the adeno-associated virus vector GfaABC1D ATP1.0 showed that exogenously applied ATP was present longer in 60TM mice than in wild-type mice. Thus, the increased ATP level caused by the decrease in its metabolizing enzyme in astrocytes could be responsible for the enhancement of microglial Ca2+ signals. To determine whether these P2Y12 receptor-mediated Ca2+ signals in AxD microglia play a significant role in the pathological mechanism, a P2Y12 receptor antagonist, clopidogrel, was administered. Clopidogrel significantly exacerbated pathological markers in AxD model mice and attenuated the morphological features of microglia, suggesting that microglia play a protective role against AxD pathology via P2Y12 receptors. Taken together, we demonstrated that microglia sense AxD astrocyte dysfunction via P2Y12 receptors as an increase in extracellular ATP and alter their morphology and Ca2+ signalling, thereby protecting against AxD pathology. Although AxD is a primary astrocyte disease, our study may facilitate understanding of the role of microglia as a disease modifier, which may contribute to the clinical diversity of AxD. [ABSTRACT FROM AUTHOR]

Published
2024
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28. Comparison of 2-octyl cyanoacrylate with polyester mesh with standard suture and staples in total knee and hip arthroplasty

Author

Koyama, Suguru, Tensho, Keiji, Takashimizu, Ikkei, Aoki, Tetsuhiro, Shimodaira, Hiroki, Iwaasa, Tomoya, Horiuchi, Hiroshi, Saito, Naoto, Yuzuriha, Shunsuke, and Takahashi, Jun

Abstract

Objective:The use of 2-octyl cyanoacrylate with polyester mesh (OCA-M) has become common in total hip and knee arthroplasty (THA, TKA). We aimed to compare the safety and cosmetic outcomes between OCA-M and standard suture techniques and staples, and determine whether OCA-M can safely be used for TKA.Method:Inclusion criteria were patients who underwent THA or TKA from January 2010 to October 2011 (Suture group), November 2011 to August 2013 (Staple group), March 2017 to September 2018 (OCA-M group). Exclusion criteria was loss of imaging data. Complications during hospitalisation (early complication) and after discharge (late complication) were compared in groups. Plastic and orthopaedic surgeons performed cosmetic evaluations with the modified Vancouver Scar Scale (VSS) and Likert scale at three and six months postoperatively and compared in groups.Results:A total of 249 arthroplasties (suture group=88 patients; staple group=94 patients; OCA-M group=67 patients) were included in the study. The OCA-M group had a significantly lower early complication rate than the suture group (p=0.015). For THA, the OCA-M group had a significantly lower total complication rate than the suture group (p=0.048). For TKA, there was no significant difference among the three groups. The complication rate in the OCA-M group showed no significant difference between THA/TKA. With regards to the VSS, the OCA-M group was significantly better for cosmetic qualities than the suture group (p=<0.001, p=0.021 at three and six months, respectively). For the Likert scale, the OCA-M group was also significantly better for cosmetic qualities than the suture group and staple group (suture–OCA-M, p=0.003 (three months), p=<0.001 (six months); staple–OCA-M, p=0.027 (three months)).Conclusion:In this study, the OCA-M complication rate was low compared to suturing and similar to stapling. Moreover, better cosmetic outcomes were achieved compared to suturing and stapling.

Published
2024
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31. Astrocytic NKCC1 inhibits seizures by buffering Cl− and antagonizing neuronal NKCC1 at GABAergic synapses.

Author

Nguyen, Trong Dao, Ishibashi, Masaru, Sinha, Adya Saran, Watanabe, Miho, Kato, Daisuke, Horiuchi, Hiroshi, Wake, Hiroaki, and Fukuda, Atsuo

Subjects
ASTROCYTES, GABAERGIC neurons, SEIZURES (Medicine), SYNAPSES, PYRAMIDAL neurons, NEUROGLIA
Abstract

Objective: A pathological excitatory action of the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) has been observed in epilepsy. Blocking the Cl− importer NKCC1 with bumetanide is expected to reduce the neuronal intracellular Cl− concentration ([Cl−]i) and thereby attenuate the excitatory GABA response. Accordingly, several clinical trials of bumetanide for epilepsy were conducted. Although NKCC1 is expressed in both neurons and glial cells, an involvement of glial NKCC1 in seizures has not yet been reported. Astrocytes maintain high [Cl−]i with NKCC1, and this gradient promotes Cl− efflux via the astrocytic GABAA receptor (GABAAR). This Cl− efflux buffers the synaptic cleft Cl− concentration to maintain the postsynaptic Cl− gradient during intense firing of GABAergic neurons, thereby sustaining its inhibitory action during seizure. In this study, we investigated the function of astrocytic NKCC1 in modulating the postsynaptic action of GABA in acute seizure models. Methods: We used the astrocyte‐specific conditional NKCC1 knockout (AstroNKCC1KO) mice. The seizurelike events (SLEs) in CA1 pyramidal neurons were triggered by tetanic stimulation of stratum radiatum in acute hippocampus slices. The SLE underlying GABAAR‐mediated depolarization was evaluated by applying the GABAAR antagonist bicuculline. The pilocarpine‐induced seizure in vivo was monitored in adult mice by the Racine scale. The SLE duration and tetanus stimulation intensity threshold and seizure behavior in AstroNKCC1KO mice and wild‐type (WT) mice were compared. Results: The AstroNKCC1KO mice were prone to seizures with lower threshold and longer duration of SLEs and larger GABAAR‐mediated depolarization underlying the SLEs, accompanied by higher Racine‐scored seizures. Bumetanide reduced these indicators of seizure in AstroNKCC1KO mice (which still express neuronal NKCC1), but not in the WT, both in vitro and in vivo. Significance: Astrocytic NKCC1 inhibits GABA‐mediated excitatory action during seizures, whereas neuronal NKCC1 has the converse effect, suggesting opposing actions of bumetanide on these cells. [ABSTRACT FROM AUTHOR]

Published
2023
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40. Clinical Outcomes and Prevalence of Sarcopenia in Patients with Moderate to Severe COVID-19

Author

Yamamoto, Shuhei, primary, Sakai, Yasunari, additional, Matsumori, Keiji, additional, Osawa, Ryuji, additional, Ito, Shun, additional, Tsukakoshi, Daichi, additional, Ohno, Tomoki, additional, Ohta, Hiroaki, additional, Ichiyama, Takashi, additional, Komatsu, Masamichi, additional, Wada, Yosuke, additional, Hanaoka, Masayuki, additional, Ikegami, Shota, additional, and Horiuchi, Hiroshi, additional

Published
2022
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42. Association between postoperative delirium and heart rate variability in the intensive care unit and readmissions and mortality in elderly patients with cardiovascular surgery

Author

Tsukakoshi, Daichi, primary, Yamamoto, Shuhei, additional, Nojima, Ippei, additional, Sato, Masaaki, additional, Furuhashi, Keisuke, additional, Takeda, Shuhei, additional, Oguchi, Natsuko, additional, Kasuga, Sho, additional, Ichimura, Hajime, additional, Wada, Yuko, additional, Seto, Tatsuichiro, additional, and Horiuchi, Hiroshi, additional

Published
2022
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46. Lemierre’s Syndrome as a Sexually Transmitted Disease Due to Porphyromonas asaccharolytica Suspected to Be Caused by Pharyngitis Due to Mycoplasma pneumoniae and Epstein-Barr Virus

Author

Ueno, Kota, primary, Horiuchi, Hiroshi, additional, Utada, Syusuke, additional, Shinomiya, Yoshie, additional, Sogo, Azusa, additional, Miyagawa, Takao, additional, Niida, Shoko, additional, Okano, Hiromu, additional, Suzuki, Naoya, additional, Otsuka, Tsuyoshi, additional, Miyazaki, Hiroshi, additional, and Furuya, Ryosuke, additional

Published
2022
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