Abstract：
BACKGROUND: We investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment.
METHODS: C57BL/6 and BALB/c mice were divided into five groups: (i) uninfected, (ii) infected with A. cantonensis, (iii) infected + 10 mg/kg albendazole, (iv) infected + 25mg/kg doxycycline, and (v) infected + 10 mg/kg albendazole + 25 mg/kg doxycycline. We administered drugs in both early treatments started at 7-day post infections (dpi) and late treatments (14 dpi) to A. cantonensis-infected C57BL/6 and BALB/c mice. To assess the impact of these treatments, we employed the Morris water maze test to evaluate spatial learning and memory abilities, and the rotarod test to measure motor coordination and balance in C57BL/6 mice. Additionally, we monitored the expression of the cytokine IL-33 and GFAP in the brain of these mice using western blot analysis.
RESULTS: In this study, A. cantonensis infection was observed to cause extensive cerebral angiostrongyliasis in C57BL/6 mice. This condition significantly affected their spatial learning and memory abilities, as assessed by the Morris water maze test, as well as their motor coordination, which was evaluated using the rotarod test. Early treatment with albendazole led to favorable recovery outcomes. Both C57BL/6 and BALB/c mice express IL-33 and GFAP after co-therapy. The differences of levels and patterns of IL-33 and GFAP expression in mice may be influenced by the balance between pro-inflammatory and anti-inflammatory signals within the immune system.
CONCLUSIONS: Combination therapy with anthelmintics and antibiotics in the early stage of A. cantonensis infection, in C57BL/6 and BALB/c mice resulted in the death of parasites in the brain and reduced the subsequent neural function damage and slowed brain damage and neurobehavior impairment. This study suggests a more effective and novel treatment, and drug delivery method for brain lesions that can decrease the neurological damage of angiostrongyliasis patients.
METHODS: C57BL/6 and BALB/c mice were divided into five groups: (i) uninfected, (ii) infected with A. cantonensis, (iii) infected + 10 mg/kg albendazole, (iv) infected + 25mg/kg doxycycline, and (v) infected + 10 mg/kg albendazole + 25 mg/kg doxycycline. We administered drugs in both early treatments started at 7-day post infections (dpi) and late treatments (14 dpi) to A. cantonensis-infected C57BL/6 and BALB/c mice. To assess the impact of these treatments, we employed the Morris water maze test to evaluate spatial learning and memory abilities, and the rotarod test to measure motor coordination and balance in C57BL/6 mice. Additionally, we monitored the expression of the cytokine IL-33 and GFAP in the brain of these mice using western blot analysis.
RESULTS: In this study, A. cantonensis infection was observed to cause extensive cerebral angiostrongyliasis in C57BL/6 mice. This condition significantly affected their spatial learning and memory abilities, as assessed by the Morris water maze test, as well as their motor coordination, which was evaluated using the rotarod test. Early treatment with albendazole led to favorable recovery outcomes. Both C57BL/6 and BALB/c mice express IL-33 and GFAP after co-therapy. The differences of levels and patterns of IL-33 and GFAP expression in mice may be influenced by the balance between pro-inflammatory and anti-inflammatory signals within the immune system.
CONCLUSIONS: Combination therapy with anthelmintics and antibiotics in the early stage of A. cantonensis infection, in C57BL/6 and BALB/c mice resulted in the death of parasites in the brain and reduced the subsequent neural function damage and slowed brain damage and neurobehavior impairment. This study suggests a more effective and novel treatment, and drug delivery method for brain lesions that can decrease the neurological damage of angiostrongyliasis patients.
摘要：
背景：我们研究了阿苯达唑和多西环素联合治疗对广州管圆线虫感染小鼠早期和晚期治疗的影响。
方法：C57BL/6和BALB/c小鼠分为五组：（i）未感染，(ii)感染了A.cantonensis,(iii)感染+10mg/kg阿苯达唑，（iv）感染+25mg/kg多西环素，和(v)感染+10mg/kg阿苯达唑+25mg/kg多西环素。我们在感染后7天（dpi）和晚期治疗（14dpi）开始的早期治疗中，对感染的C57BL/6和BALB/c小鼠施用药物。为了评估这些治疗的影响，我们使用Morris水迷宫测试来评估空间学习和记忆能力，和旋转试验测量C57BL/6小鼠的运动协调和平衡。此外,我们使用蛋白质印迹分析监测了这些小鼠脑中细胞因子IL-33和GFAP的表达。
结果：在这项研究中，在C57BL/6小鼠中观察到A.cantonensis感染引起广泛的脑血管圆线虫病。这种情况显著影响了他们的空间学习和记忆能力，根据莫里斯水迷宫测试的评估，以及他们的运动协调，这是使用旋转杆测试进行评估的。阿苯达唑的早期治疗导致良好的恢复结果。共同治疗后，C57BL/6和BALB/c小鼠均表达IL-33和GFAP。小鼠中IL-33和GFAP表达的水平和模式的差异可能受到免疫系统内促炎和抗炎信号之间的平衡的影响。
结论：抗虫药和抗生素联合治疗在广东曲霉感染早期，在C57BL/6和BALB/c小鼠中，导致大脑中寄生虫死亡，并减少了随后的神经功能损伤，减缓了脑损伤和神经行为障碍。这项研究表明了一种更有效和新颖的治疗方法，脑病变的给药方法可以减少血管圆线虫病患者的神经损伤。
方法：C57BL/6和BALB/c小鼠分为五组：（i）未感染，(ii)感染了A.cantonensis,(iii)感染+10mg/kg阿苯达唑，（iv）感染+25mg/kg多西环素，和(v)感染+10mg/kg阿苯达唑+25mg/kg多西环素。我们在感染后7天（dpi）和晚期治疗（14dpi）开始的早期治疗中，对感染的C57BL/6和BALB/c小鼠施用药物。为了评估这些治疗的影响，我们使用Morris水迷宫测试来评估空间学习和记忆能力，和旋转试验测量C57BL/6小鼠的运动协调和平衡。此外,我们使用蛋白质印迹分析监测了这些小鼠脑中细胞因子IL-33和GFAP的表达。
结果：在这项研究中，在C57BL/6小鼠中观察到A.cantonensis感染引起广泛的脑血管圆线虫病。这种情况显著影响了他们的空间学习和记忆能力，根据莫里斯水迷宫测试的评估，以及他们的运动协调，这是使用旋转杆测试进行评估的。阿苯达唑的早期治疗导致良好的恢复结果。共同治疗后，C57BL/6和BALB/c小鼠均表达IL-33和GFAP。小鼠中IL-33和GFAP表达的水平和模式的差异可能受到免疫系统内促炎和抗炎信号之间的平衡的影响。
结论：抗虫药和抗生素联合治疗在广东曲霉感染早期，在C57BL/6和BALB/c小鼠中，导致大脑中寄生虫死亡，并减少了随后的神经功能损伤，减缓了脑损伤和神经行为障碍。这项研究表明了一种更有效和新颖的治疗方法，脑病变的给药方法可以减少血管圆线虫病患者的神经损伤。
