PDF(Pubmed)
Abstract：
Reliable fluid biomarkers for evaluating neurotoxicity have yet to be established. However, recent studies have reported neurofilament light chain as a fluid biomarker of several neurodegenerative disorders. In this study, we investigated changes in the cerebrospinal fluid and plasma levels of neurofilament light chain in mice treated with trimethyltin as a neurotoxicant. Trimethyltin diluted with saline was administered by intraperitoneal injection to mice at dose levels of 0 (vehicle control), 1.0, and 2.6 mg/kg body weight (dosage volume: 10 mL/kg). At 3 or 7 days after administration, animals were euthanized by exsanguination under 2-3% isoflurane inhalation anesthesia. Increased neurofilament light chain levels in both the cerebrospinal fluid and plasma were observed in animals from the trimethyltin 2.6 mg/kg body weight group, which indicated the brain lesions including neuronal cell death. Animals from the trimethyltin 1.0 mg/kg body weight group exhibited changes neither in neurofilament light chain levels in the cerebrospinal fluid and plasma nor in the histopathology of the brain at any time point. These data indicate that plasma neurofilament light chain can serve as a useful peripheral biomarker for detecting brain lesions such as neuronal necrosis in mice.
摘要：
用于评估神经毒性的可靠的流体生物标志物尚未建立。然而,最近的研究报道了神经丝轻链作为几种神经退行性疾病的流体生物标志物。在这项研究中,我们研究了用三甲基锡作为神经毒物治疗的小鼠脑脊液和血浆神经丝轻链水平的变化。用盐水稀释的三甲基锡通过腹膜内注射以0的剂量水平(媒介物对照)给予小鼠,1.0和2.6mg/kg体重(剂量体积:10mL/kg)。在给药后3或7天，动物在2-3％异氟烷吸入麻醉下通过放血安乐死。在三甲基锡2.6mg/kg体重组的动物中观察到脑脊液和血浆中神经丝轻链水平增加，这表明脑部病变包括神经元细胞死亡。来自三甲基锡1.0mg/kg体重组的动物在任何时间点都没有表现出脑脊液和血浆中神经丝轻链水平的变化，也没有表现出脑组织病理学的变化。这些数据表明,血浆神经丝轻链可作为有用的外周生物标志物,用于检测小鼠的脑损伤如神经元坏死。
