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病例报告:用伊维菌素驱虫后出现神经症状的C57BL/6NTac和C57BL/6NCrl小鼠

Case report: C57BL/6NTac and C57BL/6NCrl mice displaying neurological signs after deworming with ivermectin.

作者信息

Eriksson M, Nylén S

机构信息

Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.

Department of Microbiology, Swedish Veterinary Agency, Uppsala, Sweden.

出版信息

Lab Anim. 2025 Jun;59(3):374-383. doi: 10.1177/00236772241286214. Epub 2024 Dec 24.

Abstract

For over 40 years, ivermectin has served as an effective anti-parasitic drug used in human and veterinary medicine. In laboratory animal facilities it is used prophylactically or therapeutically to maintain the health status of the colony or experimentally in studies. Although ivermectin is generally safe to use, there are reports of neurotoxicity associated with ivermectin crossing the blood-brain barrier due to overdosing or blood-brain barrier dysfunction. In mice, P-glycoprotein maintains the blood-brain barrier and mice with a mutation in the P-glycoprotein encoding gene are 50-100 times more sensitive to ivermectin. Signs of neurotoxicity include ataxia, bradypnea, recumbency, tremor, and death. We report neurotoxicity after ivermectin administration was used for the purpose of eradicating the murine-specific intestinal nematode in C57BL/6NTac and C57BL/6NCrl mice. The mice were dewormed by subcutaneous administration of 10 or 20 mg/kg ivermectin to eradicate all stages of . At 24-48h after deworming, 5% ( = 4) of the mice presented with tremor, ataxia, and/or head tilt. The affected mice were euthanised and gross pathological findings were found in one of the four mice (left-sided hydronephrosis). We assume that the observed neurological effects were due to defects in the blood-brain barrier, overdosing or individual sensitivity. This report provides a reason for caution when deworming laboratory mice subcutaneously with ivermectin at doses of 10 mg/kg or higher.

摘要

四十多年来,伊维菌素一直是一种有效的抗寄生虫药物,用于人类和兽医学。在实验动物设施中,它被用于预防性或治疗性地维持种群的健康状况,或在研究中进行实验使用。尽管伊维菌素一般使用安全,但有报告称,由于过量用药或血脑屏障功能障碍,伊维菌素穿过血脑屏障会导致神经毒性。在小鼠中,P-糖蛋白维持血脑屏障,编码P-糖蛋白的基因发生突变的小鼠对伊维菌素的敏感性要高50-100倍。神经毒性的症状包括共济失调、呼吸缓慢、侧卧、震颤和死亡。我们报告了在C57BL/6NTac和C57BL/6NCrl小鼠中,为根除鼠特异性肠道线虫而使用伊维菌素后出现的神经毒性。通过皮下注射10或20mg/kg伊维菌素对小鼠进行驱虫,以根除所有阶段的[线虫名称未给出]。驱虫后24-48小时,5%(n=4)的小鼠出现震颤、共济失调和/或头部倾斜。对受影响的小鼠实施安乐死,在四只小鼠中的一只发现了大体病理结果(左侧肾盂积水)。我们认为观察到的神经学效应是由于血脑屏障缺陷、用药过量或个体敏感性所致。本报告为以10mg/kg或更高剂量皮下注射伊维菌素对实验小鼠进行驱虫时需谨慎提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88a7/12120199/0006abdc0431/10.1177_00236772241286214-fig1.jpg

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