Published papers

© The Author(s) 2018. Oxidative stress plays an important role in the onset and progression of Parkinson disease. Although released dopamine at the synaptic terminal is mostly reabsorbed by dopaminergic neurons, some dopamine is presumably taken up by astroglia. This study examined the dopamine-induced astroglial protective function through the activation of the pentose-phosphate pathway (PPP) to reduce reactive oxygen species (ROS). In vitro experiments were performed using striatal neurons and cortical or striatal astroglia prepared from Sprague-Dawley rats or C57BL/6 mice. The rates of glucose phosphorylation in astroglia were evaluated using the [ 14 C]deoxyglucose method. PPP activity was measured using [1- 14 C]glucose and [6- 14 C]glucose after acute (60 min) or chronic (15 hr) exposure to dopamine. ROS production was measured using 2′,7′-dichlorodihydrofluorescein diacetate. The involvement of the Kelch-like ECH-associated protein 1 (Keap1) or nuclear factor-erythroid-2-related factor 2 (Nrf2) system was evaluated using Nrf2 gene knockout mice, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction analysis for heme oxygenase-1. Acute exposure to dopamine elicited increases in astroglial glucose consumption with lactate release. PPP activity in astroglia was robustly enhanced independently of Na + -dependent monoamine transporters. In contrast, chronic exposure to dopamine induced moderate increases in PPP activity via the Keap1/Nrf2 system. ROS production from dopamine increased gradually over 12 hr. Dopamine induced neuronal cell damage that was prevented by coculturing with astroglia but not with Nrf2-deficient astroglia. Dopamine-enhanced astroglial PPP activity in both acute and chronic manners may possibly reduce neuronal oxidative stress.

© 2018 National Stroke Association Background: The efficacy and safety of antiplatelet drugs in the treatment of moyamoya disease remain unclear. This study reports results of a nationwide survey conducted in 2016 on the trends of antiplatelet therapy for moyamoya disease in Japan. Methods: Data were obtained through questionnaires related to treatment policies regarding antiplatelet drugs from each specialized stroke management department of 765 hospitals in Japan. Data were also compared between experienced facilities (defined as facilities managing more than 10 cases per year) and those less experienced (not more than 10 cases per year) to determine experts' opinion. Results: Of the 389 departments in 375 hospitals that responded, 330 departments provided medical care for moyamoya disease. Regarding ischemic stroke, numerous departments considered the use of antiplatelet drugs “in principle” (218 departments). After surgery for ischemic moyamoya disease, the use of antiplatelet drugs for a certain period of time was the most popular opinion (74 departments). Regarding asymptomatic moyamoya disease, majority departments reported no use of APDs “in principle” (256 departments). The experienced facilities reported “no use of antiplatelet drugs” more frequently than those less experienced for treating asymptomatic moyamoya disease. In moyamoya disease, aspirin was the most commonly used antiplatelet drugs followed by cilostazol and clopidogrel. Conclusions: This survey revealed details of treatment policies, and the selection of antiplatelet drugs widely varied across facilities. Further prospective studies are necessary to improve the current unclear situation regarding the use of antiplatelet drugs for the management of moyamoya disease.

© 2017, © The Author(s) 2017. Acutely following focal cerebral ischemia disruption of the microvessel blood–brain barrier allows transit of plasma proteins into the neuropil as edema formation that coincides with loss of microvessel endothelial β1-integrins. We extend previous findings to show that interference with endothelial β1-integrin–matrix adhesion by the monoclonal IgM Ha2/5 increases the permeability of primary cerebral microvascular endothelial cell monolayers through reorganization of claudin-5, occludin, and zonula occludens-1 (ZO-1) from inter-endothelial borders. Interference with β1-integrin–matrix adhesion initiates F-actin conformational changes that coincide with claudin-5 redistribution. β1-integrin–matrix interference simultaneously increases phosphorylation of myosin light chain (MLC), while inhibition of MLC kinase (MLCK) and Rho kinase (ROCK) abolishes the Ha2/5-dependent increased endothelial permeability by 6 h after β1-integrin–matrix interference. These observations are supported by concordant observations in the cortex of a high-quality murine conditional β1-integrin deletion construct. Together they support the hypothesis that detachment of β1-integrins from abluminal matrix ligands increases vascular endothelial permeability through reorganization of tight junction (TJ) proteins via altered F-actin conformation, and indicate that the β1-integrin–MLC signaling pathway is engaged when β1-integrin detachment occurs. These findings provide a novel approach to the research and treatment of cerebral disorders where the breakdown of the blood–brain barrier accounts for their progression and complication.