一般口演（Oral）

Oral Brain Injury 一般口演脳損傷

7月27日（土）9:45～10:00　第8会場（朱鷺メッセ　3F　303+304） 3O-08m2-1 Regulating neural networks in stroke: role for the extracellular matrix remodeling Egor Dzyubenko（Dzyubenko Egor），Daniel Manrique Castano（Castano Daniel），Christoph Kleinschnitz（Kleinschnitz Christoph），Dirk M Hermann（Hermann Dirk M） University Hospital Essen, Essen, Germany Both homeostasis and plasticity of the extracellular environment of the brain are ruled out by the extracellular matrix. While brain extracellular matrix (ECM) comes in many forms, especially peculiar structures are formed around fast spiking interneurons to support their activity, called perineuronal nets (PNNs). Because interneurons are essential for the control of neural synchronization, altering the ultrastructure of PNNs can significantly affect the activity of neural networks. Although PNNs were first described by Golgi more than a century ago, they did not receive the attention they deserve before their depletion was found to rejuvenate neuronal plasticity in the mature brain. Today, we know that PNNs can restrict synapse formation, but are required to stabilize existing connections. In addition, the loss of PNNs is linked to pathogenesis of several neurological disorders, including psychosis, epilepsy, and stroke. In this work, we developed a novel approach combining superresolution structured illumination imaging (SR-SIM) and mathematical reconstruction that allows for quantitative analysis of PNN organization. Using this new method, we revealed the intermediate mode of PNN topology that can support post stroke neural rewiring. Network activity alterations induced by the ECM modifications were investigated using multiple electrode arrays (MEAs) and custom developed morphological assays in vitro. The depletion of ECM resulted in the deconstruction of PNNs and induced profound changes in network connectivity and activity patterns. In order to understand the interrelations between ECM changes, synaptic connectivity and neural activity, we performed computational modelling by implementing the experimentally defined parameters in spiking network simulations. In line with the activation of neural plasticity under stress stimuli, we suggest that subtle modification of ECM can support post injury neurologic recovery. Thus, brain ECM comprises a promising target for future restorative therapies.		7月27日（土）10:00～10:15　第8会場（朱鷺メッセ　3F　303+304） 3O-08m2-2 内包出血後のリハビリテーションにおける皮質赤核路と皮質網様体路のダイナミックな相互作用 Akimasa Ishida（石田章真）¹，Kenta Kobayashi（小林憲太）²，Yoshitomo Ueda（上田佳朋）³，Takeshi Shimizu（清水健史）¹，Naoki Tajiri（田尻直輝）¹，Tadashi Isa（伊佐正）⁴，Hideki Hida（飛田秀樹）¹ ¹名古屋市大院医脳神経生理学 ²生理研ウイルスベクター開発室 ³Dept. Otorhinolaryngol and Head and Neck Surgery, Indiana Univ. Sch. Med., Indianapolis, USA. ⁴京都大院医神経生物 Poststroke rehabilitation can enhance reorganization of the residual descending tracts to regain motor function. Although both of the cortico-rubral tract (CRT) and the cortico-reticular tract (CReT) are the potential circuits, the detailed role in poststroke rehabilitation is not clarified yet. We challenged to investigate the contribution of CRT and CReT in the rehabilitation-induced recovery after internal capsule hemorrhage (ICH). ICH was made by collagenase injection into their internal capsule. Forced impaired limb use (FLU) was given as rehabilitation for post-ICH days 1-8. Biotin dexran amine (BDA) injection into the cortex revealed that FLU induced abundant sprouting of BDA-positive fibers in the ipsilateral red nucleus, but not in the reticular formation. To investigate the contribution of the CRT and the CReT in the recovery after FLU, loss-of-function of the CRT or/and the CReT was prepared with four viral vectors: AAV-dj-CaMKII-rtTAV16 and FuG-E-TRE-EGFP.eTeNT were used to block the CRT by doxycycline, and AAV-dj-EF1α-DIO-hM4D(Gi)-mCherry and FuG-E-MSCV-Cre were used to silence the CReT by clozapine-N-oxide. CRT blockade after FLU caused impairment of the recovered forelimb function. However, the silencing of the CReT after FLU did not affect forelimb functions. Interestingly, the blockade of the CRT from the start of FLU induced obvious increase of BDA-positive sprouting in reticular formation with substantial functional recovery. Additional CReT silencing under the CRT blockade substantially worsened the recovered forelimb function. Furthermore, it revealed that the alternative recruitment of the CReT was gradually appeared under CRT blockade after FLU, in which CReT silencing caused apparent motor deficit. These findings indicated that the cortico-brainstem pathways had dynamic compensatory potentials for rehabilitation-induced functional recovery after stroke.

7月27日（土）10:15～10:30　第8会場（朱鷺メッセ　3F　303+304） 3O-08m2-3 Ror2シグナルは損傷脳内のアストロサイトが未分化性を獲得する上で重要な役割を果たす Mitsuharu Endo（遠藤光晴），Yuki Tanaka（田中祐紀），Mako Otsuka（大塚舞子），Yasuhiro Minami（南康博）神戸大院医・細胞生理 Astrocytes, a type of glial cells in the brain, play critical roles in establishing functional neural circuits during development. In the developing brain, immature astrocytes generated from neural progenitor cells proliferate to increase their number and secrete synaptogenic molecules, such as thrombospondin (TSP), to promote synapse formation. Interestingly, even in the adult brain, mature astrocytes, which are usually mitotically quiescent and play essential roles in maintaining brain homeostasis, re-acquire these immature properties following brain injury, and thereby facilitate the repair of damaged neural tissues. However, the molecular mechanism underlying how astrocytes revert to an immature state in the injured brain remains largely unknown. We have shown that in mice Ror2 receptor tyrosine kinase, which is expressed highly in neural progenitor cells and immature astrocytes but not in mature astrocytes, is induced in some populations of astrocytes surrounding injury sites in the adult brains following stab-wound injury. Ror2 has been shown to play crucial roles in regulating cellular polarity, migration, proliferation, and differentiation during developmental morphogenesis and tissue-/organo-genesis. Here, we found that Ror2 is induced strongly in mature astrocytes following stimulation with both bFGF and IL-1β, and that Ror2 signaling might play critical roles in regulating proliferation of and expression of TSP2 in astrocytes surrounding injury sites. Furthermore, we also provide evidence that expression of Ror2 might be epigenetically silenced in astrocytes in the aged brain possibly due to age-associated chromatin alterations. Our findings help to clarify how astrocytes acquire the tissue remodeling ability in the adult brain following injury.		7月27日（土）10:30～10:45　第8会場（朱鷺メッセ　3F　303+304） 3O-08m2-4 神経活動依存的な転写因子Npas4は脳梗塞に伴う細胞死を抑制する Hiroo Takahashi（高橋弘雄）^1,2，Ryo Asahina（朝比奈諒）²，Tohru Yamamoto（山本融）¹，Akio Tsuboi（坪井昭夫）^2,3 ¹香川大医分子神経生物 ²奈良医大 ³大阪大 Cerebral ischemia causes frequently death and disability; yet, the therapeutic approaches have been so far limited. After stroke, most of neurons die in the ischemic core region, leading to induction of the severe brain dysfunction. Here we have studied mechanisms that regulate neuronal survival around the infarct area, to develop a novel therapy for ischemic stroke. To investigate the profile of gene expression, which is induced immediately after middle cerebral artery occlusion (MCAO) in mice, RNA samples were prepared from the control and ischemic sides of neocortex at 2 h after stroke and subjected to RNA-Seq analysis. Among 37 candidate genes obtained from RNA-Seq, we found by in situ hybridization that 25 genes were expressed more abundantly in the ischemic side than the control side of cortex. Notably, the activity-dependent transcription factor gene, Npas4, was significantly induced in both excitatory and inhibitory neurons around the infarct cortex. We previously reported that Npas4 usually facilitates the dendritic spine formation in the olfactory bulb interneurons (Yoshihara et al., Cell Reports 8, 843-857, 2014), suggesting its role in restoring neurons from the infarct cortex. Then, we performed the loss- and gain-of-functions for Npas4 followed by MCAO. Npas4 knockout mice following MCAO showed an increase of the infract size and the severe behavioral dysfunction. Interestingly, transient induction of Npas4 expression before MCAO gave rise to a reduction of the infract size, compared with the control. Since we recently identified a target gene downstream of Npas4, our findings suggest that Npas4 expression, induced immediately after stroke, plays crucial roles in neuronal survival in the brain.