一般口演（Oral）

Oral Brain Ischemia 一般口演脳虚血

7月27日（土）8:45～9:00　第8会場（朱鷺メッセ　3F　303+304） 3O-08m1-1 Ropinirole targets mitochondria permeability transition pore in a rodent model of ischemic stroke Heena Tabassum（Tabassum Heena）¹，Syed S Andrabi（Andrabi Syed）²，Suhel Parvez（Parvez Suhel）² ¹Indian Council of Medical Research ²Department of Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India Dopamine D2 receptor agonist, Ropinirole, has been found to promote neuroprotection in Parkinson disease and restless leg syndrome. Recent evidences have shown that Ropinirole mediates its neuroprotection through mitochondria. Assuming this, we examined the possible mitochondrial role of Ropinirole in promoting the neuroprotection in ischemic stroke of rat. Male Wistar rats underwent transient middle cerebral artery occlusion and then received the Ropinirole (10 mg and 20 mg/kg b.w.) at 1 h, 6, 12 and 18 h post occlusion. The panel of neurological tests and infarct size were performed after 24 h of the ischemia. Flow cytometry was used to detect the mitochondrial membrane potential, ROS and Ca2+ respectively. Mitochondrial bioenergetics was analyzed by oxygraph. Western blotting was used to analyze the expression of various proteins such as Bax, Bcl-2 and cytochrome c. Ropinirole induced neurological recovery as shown by the panel of neurobehavioural tests and 2, 3, 5-triphenyltetrazolium chloride staining. Post stroke treatment with Ropinirole reduced the mitochondrial ROS and Ca2+ in tMCAO rats. In addition, Ropinirole elevated the mitochondrial membrane potential and mitochondria bioenergetics. Western blotting showed that Ropinirole inhibited the translocation of cytochrome c from mitochondria to cytosol. Overall, post stroke administration of Ropinirole facilitated neurological recovery through mitochondrial pathways in ischemic/reperfusion injury.		7月27日（土）9:00～9:15　第8会場（朱鷺メッセ　3F　303+304） 3O-08m1-2 新規胎発育遅延モデルラットの作製と臍帯由来間葉系細胞による治療法開発 Yoshiaki Sato（佐藤義朗）¹，Yuma Kitase（北瀬悠磨）¹，Atsuto Onoda（小野田淳人）^1,4，Ryosuke Miura（三浦良介）¹，Shoji Go（呉尚治）¹，Mahboba Jabary（Jabary Mahboba）¹，Kazuto Ueda（上田一仁）¹，Haruka Mimatsu（見松はるか）¹，Toshihiko Suzuki（鈴木俊彦）¹，Takeo Mukai（向井丈雄）²，Tokiko Nagamura-Inoue（長村登紀子）²，Masahiro Tsuji（辻雅弘）³，Masahiro Hayakawa（早川昌弘）¹ ¹名古屋大学医学部附属病院　総合周産期母子医療センター　新生児部門 ²東京大学医科学研究所分子療法分野　セルプロセッシング輸血部 ³京都女子大学家政学部食物栄養学科 ⁴日本学術振興会特別研究員PD [Objective] Chronic mild intrauterine hypoperfusion in fetal growth restriction (FGR) induced by hypertension during pregnancy could cause postnatal neurological disorders and there is not currently an established treatment. The purposes in the present study were to develop a FGR rat model using chronic mild intrauterine hypoperfusion and to examine the treatment effects of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs). [Methods] To create the chronic mild intrauterine hypoperfusion, we used an ameroid constrictor that had titanium on the outer wall and was C-shaped with a notch and center hole inside; thus it gradually narrowed the center hole when absorbing water. We applied ameroid constrictors bilaterally to both upper uterine ovarian and lower uterine arteries on day 17 of pregnancy. The pups were born by natural delivery and regarded as FGR model rats. We administered 1 × 10⁵ UC-MSCs (U group) or vehicle (V group) intravenously to FGR pups via the right external jugular vein 4 days after birth. Various behavioral experiments were conducted from the 10th day of birth, and immunohistological evaluation was performed at 2 months after birth. [Results] The blood flow was measured by a laser measuring instrument, and it was reduced gradually to 60% 72 hours after the ameroid constrictors were applied. The body weight of the FGR pups at birth was significantly lower (p < 0.01). The negative geotaxis used to evaluate the primitive reflex showed that the time required to reorient to a head-upward position in the V group was significantly longer (p < 0.0001) than that for sham rats (S group) and the reorientation time in the U group was significantly shorter than that in the V group (p < 0.01). In the rotarod test to evaluate motor coordination and motor learning at five months after birth, the latency to fall in the U group was significantly longer than that in the V group (p < 0.05). In the immunohistological evaluation, the total number of neurons (NeuN positive cells) counted by the stereology method in the cortex was decreased in the V group compared to the S group (p < 0.0001), and the decrease was ameliorated in the U group (p < 0.01). [Conclusion] We developed a novel FGR model using by chronic mild intrauterine hypoperfusion. FGR showed neurological abnormalies both behaviorally and histologically. UC-MSCs exerted a treatment effect for the neurological disorders in the neonatal FGR rats.

7月27日（土）9:15～9:30　第8会場（朱鷺メッセ　3F　303+304） 3O-08m1-3 Multilineage-differentiating stress enduring cell製剤の新生児低酸素性虚血性脳症に対する治療効果の検討 Kazuto Ueda（上田一仁）¹，Yoshiaki Sato（佐藤義朗）¹，Toshihiko Suzuki（鈴木俊彦）¹，Atsuto Onoda（小野田淳人）¹，Ryousuke Miura（三浦良介）¹，Shoji Go（呉尚治）¹，Haruka Mimatsu（見松はるか）¹，Yuma Kitase（北瀬悠磨）¹，Yuta Yamashita（山下郁太）³，Keiichi Irie（入江圭一）³，Masahiro Tsuji（辻雅弘）²，Kenichi Mishima（三島健一）³，Shinobu Shimizu（清水忍）⁴，Masahiro Hayakawa（早川昌弘）¹ ¹名古屋大学医学部附属病院　総合周産期母子医療センター　新生児部門 ²京都女子大学　家政部　食物栄養学科 ³福岡大学　薬学部 ⁴名古屋大学医学部附属病院　先端医療開発部　先端医療・臨床研究支援センター [Background] Perinatal hypoxic-ischemia (HI) can lead to severe neurological deficits or even neonatal death. Cell therapy has been developed as a novel treatment for HI. Multilineage-differentiating stress-enduring (Muse) cells are pluripotent stem cells positive for the SSEA-3 marker that readily integrate into the injured sites and mediate tissue repair. We have previously reported the therapeutic effect of Muse cells in HI model rats. In this study, the therapeutic effect of an administered clinical grade Muse cell product (CL2020) against acute HI injury was evaluated in a rat model towards an exploratory investigator-initiated clinical trial. [Methods] Seven-day-old rats underwent left carotid artery ligation and were exposed to 8% oxygen for 60 min. The damage in the cerebral hemisphere was evaluated by T2-weighted magnetic resonance imaging, and moderately or severely HI-injured rats were selected on postnatal day 10. The selected rats were assigned to three groups: CL2020 administration (1 × 10⁶ cells/body) 3 days after HI insult (M3 group), CL2020 administration (1 × 10⁶ cells/body) 7 days after HI insult (M7 group), and HBSS administration (vehicle group). CL2020 was administered via the right external jugular vein. Behavioral assessments using the cylinder, open field, and water maze tests were performed in 5-8-week-old rats. This study was approved by the Institutional Review Board of Nagoya University School of Medicine. [Results] In the cylinder test, both the M3 and M7 groups showed significant improvement compared with the vehicle-treated group (p < 0.01 and p < 0.05, respectively). In the open field test, the distance traveled by the rats with moderate injury in the M7 group showed significant improvement compared with the distance traveled by the vehicle-treated group (p < 0.05). In the water maze test, the distance traveled showed a tendency to improve in moderately injured rats. [Conclusion] These results indicate that intravenous administration of CL2020 ameliorates neonatal HI brain injury both three and seven days after insult and its therapeutic effect is greater in rats with moderate brain injury.		7月27日（土）9:30～9:45　第8会場（朱鷺メッセ　3F　303+304） 3O-08m1-4 脳虚血モデルラットにおけるイミプラミンの認知機能改善効果と海馬CA1領域における神経分化促進作用 Jiro Kasahara（笠原二郎），Koko Masamune（政宗宏子），Kenta Tezuka（手塚健太），Natsuko Murakami（村上夏子）徳島大院薬神経病態解析 Transient focal cerebral ischemia rapidly causes severe damage in the ischemic core region. It also can cause neuronal damage in the area distant from ischemic core within a few days to weeks. Hippocampus is one of such a remote area known to display delayed neuronal death after ischemia. Pyramidal neurons in the hippocampal CA1 region are especially vulnerable to ischemic stress such as middle cerebral artery occlusion (MCAO) in a rodent model of ischemia, leading to higher brain dysfunction in chronic stage. In this study, we evaluated cognitive dysfunction after MCAO in rats both with Y-maze and novel object recognition tests, and examined the effect of chronic imipramine treatment on it. Transient MCAO for 90 min caused significant neuronal loss in CA1 within a week, together with significantly decreased % alternation in Y-maze and % exploration time for novel object. Chronic imipramine treatment with 20 mg/kg/day for 7 weeks from 1 week after MCAO significantly recovered the results of both behavioral tests to the levels of sham-operated group. Immunohistochemical analysis revealed that chronic imipramine treatment in MCAO rats significantly recovered the number of matured neurons characterized by NeuN in CA1. We also examined the expression of Nestin, a neural progenitor marker, Doublecortin, an early neuronal marker, and Calretinin, a post-mitotic neuronal marker in CA1. The results suggested that Nestin-positive cells were accumulated after 1 week from MCAO in CA1 and differentiate into Doublecortin-positive cells, while chronic imipramine treatment facilitate these cells to maturate more into NeuN-positive neurons via Calretinin-positive. Together with our previously reported results that chronic imipramine treatment in MCAO rats alleviated aggravation of anhedonia characterized by the sucrose preference test, with protecting granular cells in dentate gyrus from apoptosis, this study showed beneficial effects of imipramine on hippocampus after transient focal cerebral ischemia.