Browsing by Author "Mori, Shusuke"

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    Abnormal Cardiac Repolarization After Seizure Episodes in Structural Brain Diseases: Cardiac Manifestation of Electrical Remodeling in the Brain?
    (American Heart Association, 2021-05-04) Mori, Shusuke; Hori, Atsushi; Turker, Isik; Inaji, Motoki; Bello-Pardo, Erika; Miida, Takashi; Otomo, Yasuhiro; Ai, Tomohiko; Medicine, School of Medicine
    Background: Abnormal cardiac repolarization is observed in patients with epilepsy and can be associated with sudden death. We investigated whether structural brain abnormalities are correlated with abnormal cardiac repolarizations in patients with seizure or epilepsy. Methods and Results: We retrospectively analyzed and compared 12-lead ECG parameters following seizures between patients with and without structural brain abnormalities. A total of 96 patients were included: 33 women (17 with and 16 without brain abnormality) and 63 men (44 with and 19 without brain abnormality). Brain abnormalities included past stroke, chronic hematoma, remote bleeding, tumor, trauma, and postsurgical state. ECG parameters were comparable for heart rate, PR interval, and QRS duration between groups. In contrast, corrected QT intervals evaluated by Fridericia, Framingham, and Bazett formulas were prolonged in patients with brain abnormality compared with those without (women: Fridericia [normal versus abnormal], 397.4±32.7 versus 470.9±48.9; P=0.002; Framingham, 351.0±40.1 versus 406.2±46.1; P=0.002; Bazett, 423.8±38.3 versus 507.7±56.6; P<0.0001; men: Fridericia, 403.8±30.4 versus 471.0±47.1; P<0.0001; Framingham, 342.7±36.4 versus 409.4±45.8; P<0.0001; Bazett, 439.3±38.6 versus 506.2±56.8; P<0.0001). QT dispersion and Tpeak-Tend intervals were comparable between groups. We also observed abnormal ST-segment elevation in 5 patients. Importantly, no patients showed fatal arrhythmias during or after seizures. Conclusions: Our study demonstrated that brain abnormalities can be associated with abnormal cardiac repolarization after seizures, which might be a manifestation of electrophysiological remodeling in the brain.
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    Carvedilol suppresses ryanodine receptor-dependent Ca2+ bursts in human neurons bearing PSEN1 variants found in early onset Alzheimer's disease
    (Public Library of Science, 2024-08-22) Hori, Atsushi; Inaba, Haruka; Hato, Takashi; Tanaka, Kimie; Sato, Shoichi; Okamoto, Mizuho; Horiuchi, Yuna; Paran, Faith Jessica; Tabe, Yoko; Mori, Shusuke; Rosales, Corina; Akamatsu, Wado; Murayama, Takashi; Kurebayashi, Nagomi; Sakurai, Takashi; Ai, Tomohiko; Miida, Takashi; Medicine, School of Medicine
    Seizures are increasingly being recognized as the hallmark of Alzheimer's disease (AD). Neuronal hyperactivity can be a consequence of neuronal damage caused by abnormal amyloid β (Aß) depositions. However, it can also be a cell-autonomous phenomenon causing AD by Aß-independent mechanisms. Various studies using animal models have shown that Ca2+ is released from the endoplasmic reticulum (ER) via type 1 inositol triphosphate receptors (InsP3R1s) and ryanodine receptors (RyRs). To investigate which is the main pathophysiological mechanism in human neurons, we measured Ca2+ signaling in neural cells derived from three early-onset AD patients harboring Presenilin-1 variants (PSEN1 p.A246E, p.L286V, and p.M146L). Of these, it has been reported that PSEN1 p.A246E and p.L286V did not produce a significant amount of abnormal Aß. We found all PSEN1-mutant neurons, but not wild-type, caused abnormal Ca2+-bursts in a manner dependent on the calcium channel, Ryanodine Receptor 2 (RyR2). Indeed, carvedilol, an RyR2 inhibitor, and VK-II-86, an analog of carvedilol without the β-blocking effects, sufficiently eliminated the abnormal Ca2+ bursts. In contrast, Dantrolene, an inhibitor of RyR1 and RyR3, and Xestospongin c, an IP3R inhibitor, did not attenuate the Ca2+-bursts. The Western blotting showed that RyR2 expression was not affected by PSEN1 p.A246E, suggesting that the variant may activate the RyR2. The RNA-Seq data revealed that ER-stress responsive genes were increased, and mitochondrial Ca2+-transporter genes were decreased in PSEN1A246E cells compared to the WT neurons. Thus, we propose that aberrant Ca2+ signaling is a key link between human pathogenic PSEN1 variants and cell-intrinsic hyperactivity prior to deposition of abnormal Aß, offering prospects for the development of targeted prevention strategies for at-risk individuals.
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    A Case of Fatal Stanford Type A Aortic Dissection Caused by a Traffic Accident with Low Energy Impact
    (Dove Press, 2020-10-14) Mori, Shusuke; Ai, Tomohiko; Morishita, Koji; Otomo, Yasuhiro; Medicine, School of Medicine
    A seemingly healthy 84-year-old female pedestrian was mildly bumped by a car, and she hit her left shoulder, flank, and lower legs when she fell down on a street. She was conscious and stable when transferred to an emergency room. She had no sign of any major injuries except minor lacerations on her legs. Repeated evaluations including chest X-ray, ECG, and focused assessment with sonography for trauma did not reveal any abnormal findings. While waiting for discharge, she started having mild chest discomfort. Unexpectedly, the third echocardiogram showed mild pericardial effusion, and a CT with contrast showed aortic dissection in the ascending aorta and infra-left subclavian aortic dissection. She was immediately transferred by a helicopter to a tertiary trauma center for emergent repair surgery. Considering the site of dissections, progression of existing intrinsic intimal tear triggered by energy impact was suspected. However, traumatic causes could not be excluded. Extra caution and diligence should be exercised when examining elderly patients in blunt trauma.