東京大学医科学研究所

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学友会セミナー

学友会セミナー:2018年11月21日

開催日時: 2018年11月21日 18:00 ~ 19:00
開催場所: 1号館 2-3会議室
講師: Jacques-Olivier
所属: Senior CNRS Researcher、Institut de Neurosciences de la Timone (INT), UMR7289 CNRS, Aix-Marseille Université, Marseille, France
演題: Mild intrauterine hypoperfusion leads to muscle, gait, sensorimotor and cognitive dysfunctions: implications for prematurity and cerebral palsy
概要:

Perinatal hypoxia- ischemia is detrimental to the developing brain and leads to white matter injury (WMI), encephalopathy of prematurity (EP) and often to cerebral palsy (CP), but the related pathophysiological mechanisms remain unclear. In prior studies, we used mild intrauterine hypoperfusion (MIUH or prenatal ischemia at embryonic day 17) in rats that successfully reproduced the diversity of clinical signs of EP, and some CP symptoms. Briefly, MIUH led to inflammatory processes, diffuse grey and WMI, minor locomotor deficits, musculoskeletal pathologies, neuroanatomical and functional disorganization of the somatosensory and prefrontal cortex and hippocampal complex, delayed sensorimotor reflexes, spontaneous hyperactivity, deficits in sensory information processing, memory and learning impairments in adult rats. Recently, we investigated the early and long-lasting mechanisms of pathophysiology that may be responsible for the various symptoms induced by MIUH. Adult MIUH rats exhibited changes in muscle contractile properties and phenotype, enduring hyperreflexia and spasticity, as well as hyperexcitability in the sensorimotor cortex. MIUH induces early hyperreflexia, spasticity and reduced expression of KCC2 (a chloride cotransporter that regulates chloride homeostasis and cell excitability). Taken together, these results show that reduced expression of KCC2, lumbar hyperreflexia, spasticity, altered properties of the soleus muscle, as well as cortical hyperexcitability. Each of these disorders appear to interplay into self-perpetuating cycles, leading to the emergence and persistence of neurodevelopmental disorders in EP and CP, such as sensorimotor impairments, and likely hyperactivity, attention and learning disorders. In addition, we are investigating a prevention lead based on mesenchymal stem cells that appears very promising.

世話人: 〇長村 登紀子 (セルプロセッシング・輸血部)
 大津 真 (幹細胞プロセシング分野)