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Neurosteroids as stress modulators and neurotherapeutics: lessons from the retina

Neural Regeneration Research 2023年第5期18卷 1004-1008页

作者： Yukitoshi Izumi Makoto Ishikawa toru nakazawa Hiroshi Kunikata Kota Sato Douglas F.Covey Charles F.Zorumski Department of Psychiatry and Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA Department of Ophthalmic Imaging and Information Analytics Tohoku University Graduate School of MedicineSendaiJapan Department of Ophthalmology Tohoku University Graduate School of MedicineSendaiJapan Department of Retinal Disease Control Tohoku University Graduate School of MedicineSendaiJapan Department of Advanced Ophthalmic Medicine Tohoku University Graduate School of MedicineSendaiJapan Department of Developmental Biology Washington University School of MedicineSt.LouisMOUSA

Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon. These steroids have unique properties, including neuroprotective effects that could benefit a wide range of brain illnesses including depression, anxiety, epilepsy, and neurodegeneration. Over the past 25 years, our group has developed ex vivo rodent models to examine factors contributing to several forms of neurodegeneration in the retina. In the course of this work, we have developed a model of acute closed angle glaucoma that involves incubation of ex vivo retinas under hyperbaric conditions and results in neuronal and axonal changes that mimic glaucoma. We have used this model to determine neuroprotective mechanisms that could have therapeutic implications. In particular, we have focused on the role of both endogenous and exogenous neurosteroids in modulating the effects of acute high pressure. Endogenous allopregnanolone, a major stress-activated neurosteroid in the brain and retina, helps to prevent severe pressure-induced retinal excitotoxicity but is unable to protect against degenerative changes in ganglion cells and their axons under hyperbaric conditions. However, exogenous allopregnanolone, at a pharmacological concentration, completely preserves retinal structure and does so by combined effects on gamma-aminobutyric acid type A receptors and stimulation of the cellular process of macroautophagy. Surprisingly, the enantiomer of allopregnanolone, which is inactive at gamma-aminobutyric acid type A receptors, is equally retinoprotective and acts primarily via autophagy. Both enantiomers are also equally effective in preserving retinal structure and function in an in vivo glaucoma model. These studies in the retina have important implications for the ongoing development of allopregnanolone and other neurosteroids as therapeutics for neuropsychiatric illnesses.

关键词： allopregnanolone autophagy enantiomers excitotoxicity gamma-aminobutyric acid type A receptors glaucoma optic nerve oxysterols

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Combined Surgery in Keratoplasty

Combined Surgery in Keratoplasty

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中华医学会第十二届全国眼科学术大会

作者： toru nakazawa Tohoku University Graduate School of Medicine Japan

It has been 100 years since the first successful penetrat- ing keratoplasty(PKP).Recently,a variety of procedures, including deep lamellar keratoplasty(DLKP)and Descemet’s

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一氧化氮合成酶抑制剂L-NAME减少光动力治疗后视网膜感光细胞损伤的实验研究

一氧化氮合成酶抑制剂L-NAME减少光动力治疗后视网膜感光细胞损伤...

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中华医学会第十二届全国眼科学术大会

作者：余海澄 toru nakazawa Akihisa Matsubara Toshio Hisatomi Tara A．Young Norman Michaud Edward Connolly Ali Hafezi—Moghadam Evangelos S．Gragoudas Joan W．Miller 首都医科大学附属北京同仁医院

目的：用激光诱导的脉络膜新生血管(choroidal neovascu- larization,CNV)动物模型研究一氧化氮合成酶(nitric ox- ide synthase,NOS)在光动力治疗(photodynamic ther- aphy,PDT)后的视网膜感光细胞损伤中起的作用。方法：

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Usefulness of autotaxin for the complications of liver cirrhosis

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World Journal of Gastroenterology 2020年第1期26卷 97-108页

作者： Xue Shao Haruki Uojima toru Setsu Tomomi Okubo Masanori Atsukawa Yoshihiro Furuichi Yoshitaka Arase Hisashi Hidaka Yoshiaki Tanaka Takahide nakazawa Makoto Kako Tatehiro Kagawa Katsuhiko Iwakiri Shuji Terai Wasaburo Koizumi Department of Gastroenterology Internal MedicineKitasato University School of MedicineSagamiharaKanagawa 252-0375Japan Department of Hepatopancreatobiliary Medic Department of Gastroenterology Shonan Kamakura General HospitalKamakuraKanagawa 247-8533Japan Division of Gastroenterology and Hepatology Graduate School of Medical and Dental SciencesNiigata UniversityNiigata 951-8510Japan Department of Internal Medicine Division of GastroenterologyNippon Medical School Chiba Hokusoh HospitalChiba 270-1694Japan Department of Internal Medicine Division of Gastroenterology and HepatologyNippon Medical SchoolTokyo 113-8603Japan Department of Gastroenterology and Hepatology Tokyo Medical University HospitalShinjukuTokyo 113-8510Japan Division of Gastroenterology and Hepatology Department of Internal MedicineTokai University School of MedicineKanagawa 259-1193Japan

BACKGROUND Autotaxin(ATX)has been reported as a direct biomarker for estimating the evaluation of liver *** available data on ATX as a useful biomarker for the complications of liver cirrhosis(LC)are *** To assess the clinical usefulness of ATX for assessing the complications of *** This multicenter,retrospective study was conducted at six locations in *** include patients with LC,n=*** ATX level was evaluated separately in men and women because of its high level in female *** assess the clinical usefulness of ATX for the complications of LC,the area under the curve(AUC)of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score,albumin-bilirubin(ALBI)score,fibrosis-4 index,and aspartate aminotransferase-to-platelet ratio *** The mean age was 68.4±11.4 years,240 patients(60.0%)were male.A total of 213(53.3%)and 187(46.8%)patients were compensated and decompensated,*** numbers of patients with varix rupture,hepatic ascites,and hepatic encephalopathy were 35(8.8%),131(32.8%),and 103(25.8%),*** AUCs of ATX in men for hepatic encephalopathy,hepatic ascites,and varix ruptures were 0.853,0.816,and 0.706,*** AUCs of ATX in women for hepatic encephalopathy,hepatic ascites,and varix rupture were 0.759,0.717,and 0.697,*** AUCs of ATX in men were higher than those in women,as were all the other biomarkers used to detect encephalopathy and varix ***,for detecting ascites,the AUC of ALBI in men was more effective than using *** ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.

关键词： Autotaxin Hepatic encephalopathy Hepatic ascites Liver fibrosis Biomarker

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