사람 배아 줄기세포로부터 얻어낸 신경 전구세포의 생존, 증식, 아포토시스, 분화에 대한 세보플루란 단기 노출의 영향

Abstract

학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과, 2018. 2. 김진희.Purpose: Data from animal experiments suggest that exposure to general anesthetics in early life inhibits neurogenesis and causes long-term memory deficit. Regarding a short operating time and popularity of sevoflurane in pediatric anesthesia, it is important to verify effects of short period exposure to sevoflurane on developing brain. Methods: We measured the effects of short-term exposure (2 h) to 3%, 6% or 8% sevoflurane, the most commonly used anesthetic, on neural precursor cells derived from human embryonic stem cells, SNUhES32. On days 1, 3, 5 and 7 post-treatment, cell survival, proliferation, apoptosis and differentiation were analyzed. Results: Treatment with 6% sevoflurane increased cell viability (P = 0.046) and decreased apoptosis (P = 0.014) on day 5, but didnt last on day 7. Survival and apoptosis were not affected by 3% and 8% sevofluranethere was no effect of proliferation at any of the tested concentrations. The differentiation of cells exposed to 6% or 8% sevoflurane decreased on day 1 (P = 0.033 and 0.036 for 6% and 8% sevoflurane, respectively) but was again normalized on days 3–7. Conclusion: The clinically relevant treatment with sevoflurane for 2 h induces no significant changes of the survival, proliferation, apoptosis and differentiation of human neural precursor cells, although supra-clinical doses of sevoflurane alter human neurogenesis transiently.1. Introduction 1 2. Materials and Methods 3 hESC line 3 Derivation of NPCs from hESCs 3 Sevoflurane treatment 4 Determination of the medium concentration of sevoflurane by gas chromatography 5 Cell viability analysis 5 Proliferation analysis 5 Apoptosis analysis 6 Differentiation analysis 6 Statistical analysis 7 3. Result 8 Concentration of sevoflurane in the medium 8 Effects of sevoflurane on the survival of human NPCs 8 Effects of sevoflurane on the proliferation of human NPCs 9 Effects of sevoflurane on apoptosis by human NPCs 10 Effects of sevoflurane on human NPC differentiation 11 4. Discussion 12 5. References 17Docto

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