運動負荷はパーキンソン病モデルラットにおいて移植されたドーパミンニューロンの軸索を線条体背外側へ誘導する

京都大学新制・課程博士博士(医学)甲第23095号医博第4722号新制||医||1050(附属図書館)京都大学大学院医学研究科医学専攻(主査)教授 伊佐 正, 教授 井上 治久, 教授 渡邉 大学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Pretreatment with Perlecan-Conjugated Laminin-E8 Fragment Enhances Maturation of Grafted Dopaminergic Progenitors in Parkinson’s Disease Model

The therapeutic effect of a cell replacement therapy for Parkinson's disease (PD) depends on the proper maturation of grafted dopaminergic (DA) neurons and their functional innervation in the host brain. In the brain, laminin, an extracellular matrix protein, regulates signaling pathways for the survival and development of neurons by interacting with integrins. The heparan sulfate (HS) chain binds mildly to various neurotrophic factors and regulates their intracellular signaling. Perlecan-conjugated laminin 511/521-E8 fragments (p511/p521) were designed to contain an integrin-binding site and HS chains. Here we examined the effect of treating DA progenitors with p511/p521 prior to transplantation in rodent PD models. In vitro and in vivo experiments showed that p511/p521 treatment enhanced the maturation and neurite extension of the grafted DA progenitors by activating RAS-ERK1/2 signaling. This strategy will contribute to an efficient cell replacement therapy for PD in the future

A peripartum major cerebral infarction in a patient with moyamoya disease following previous bilateral STA-MCA anastomosis: A case report

Background: Although the incidence is rare, patients with moyamoya disease are at risk of stroke during pregnancy. Therefore, there is limited information regarding appropriate peripartum management. Herein, we report a case of major postpartum cerebral infarction in a patient with moyamoya disease, despite previous direct bilateral anastomosis of the superficial temporal artery to the middle cerebral artery (STA-MCA). Case description: The patient was a 32-year-old woman who had undergone direct STA-MCA anastomosis and encephalo-myo-synangiosis in her childhood. This was her second pregnancy. She sustained a major ischemic stroke in the left middle cerebral artery area on postpartum day 3, which resulted in right hemiplegia and aphasia. On magnetic resonance angiography, simultaneous interruption of antegrade flow of the left middle cerebral artery and STA-MCA anastomosis was observed. The patency of these vessels was confirmed before the first pregnancy. The patient’s consciousness was impaired for several days due to edema in the infarct area. However, her condition improved following conservative treatment with osmotic diuretics and antiplatelet therapy; the patient recovered independent gait and her aphasia improved after 5 months of inpatient rehabilitation. Conclusions: Careful monitoring of women with moyamoya disease is recommended during pregnancy and the peripartum period even if direct or indirect anastomosis has been previously performed