Department of Pediatrics, College of Medicine, Korea University, Seoul, Republic of Korea.
Division of Neonatology, Department of Pediatrics, Korea University Guro Hospital, Ulsan, Gyeonggi-do, Republic of Korea.
Pediatr Res. 2023 Mar;93(4):845-851. doi: 10.1038/s41390-022-02186-6. Epub 2022 Jul 19.
Chlorhexidine gluconate (CHG) is a topical antiseptic solution recommended for skin preparation before central venous catheter placement and maintenance in adults and children. Although CHG is not recommended for use in children aged <2 months owing to limited safety data, it is commonly used in neonatal intensive care units worldwide. We used zebrafish model to verify the effects of early-life exposure to CHG on the developing nervous system, highlighting its impact on oligodendrocyte development and myelination.
Zebrafish embryos were exposed to different concentrations of CHG from 4 h post fertilization to examine developmental toxicity. The hatching rate, mortality, and malformation of the embryos/larvae were monitored. Oligodendrocyte lineage in transgenic zebrafish embryos was used to investigate defects in oligodendrocytes and myelin. Myelin structure, locomotor behavior, and expression levels of genes involved in myelination were investigated.
Exposure to CHG significantly induced oligodendrocyte defects in the central nervous system, delayed myelination, and locomotor alterations. Ultra-microstructural changes with splitting and fluid-accumulated vacuoles between the myelin sheaths were found. Embryonic exposure to CHG decreased myelination, in association with downregulated mbpa, plp1b, and scrt2 gene expression.
Our results suggest that CHG has a potential for myelin toxicity in the developing brain.
To date, the neurodevelopmental toxicity of chlorhexidine gluconate (CHG) exposure on the developing brains of infants remains unknown. We demonstrated that CHG exposure to zebrafish larvae resulted in significant defects in oligodendrocytes and myelin sheaths. These CHG-exposed zebrafish larvae exhibited structural changes and locomotor alterations. Given the increased CHG use in neonates, this study is the first to identify the risk of early-life CHG exposure on the developing nervous system.
葡萄糖酸氯己定（CHG）是一种局部抗菌溶液，推荐用于成人和儿童中心静脉置管前的皮肤准备。尽管由于安全性数据有限，不建议 2 个月以下的儿童使用 CHG，但它在全球新生儿重症监护病房中被广泛使用。我们使用斑马鱼模型来验证早期接触 CHG 对发育中神经系统的影响，强调其对少突胶质细胞发育和髓鞘形成的影响。
从受精后 4 小时开始，将斑马鱼胚胎暴露于不同浓度的 CHG 中，以检查发育毒性。监测胚胎/幼虫的孵化率、死亡率和畸形。使用转基因斑马鱼胚胎中的少突胶质细胞谱系来研究少突胶质细胞和髓鞘的缺陷。研究髓鞘结构、运动行为以及参与髓鞘形成的基因的表达水平。
暴露于 CHG 显著诱导中枢神经系统中的少突胶质细胞缺陷、髓鞘形成延迟和运动行为改变。发现髓鞘之间有超微结构变化，有分裂和充满液体的空泡。胚胎暴露于 CHG 会减少髓鞘形成，与 mbpa、plp1b 和 scrt2 基因表达下调有关。
我们的结果表明 CHG 对发育中的大脑有潜在的髓鞘毒性。
迄今为止，CHG 暴露对婴儿发育中大脑的神经发育毒性仍不清楚。我们证明 CHG 暴露于斑马鱼幼虫导致少突胶质细胞和髓鞘鞘显著缺陷。这些 CHG 暴露的斑马鱼幼虫表现出结构变化和运动行为改变。鉴于新生儿中 CHG 使用增加，本研究首次确定了早期 CHG 暴露对发育中神经系统的风险。
