Journal Article

Doxycycline cotherapy with albendazole relieves neural function damage in C57BL/6 and BALB/c mice infected with Angiostrongylus cantonensis

Sofiyatun, Eny, Chen, Wei-June, Day, Yi-An, Lee, Hsin-Chia, Chen, Kuang-Yao, Chou, Chih-Jen, Chiang, Pei-Jui, Jhan, Kai-Yuan, Chiu, Cheng-Hsun, Wang, Lian-Chen

2025

Overview

We investigated the effects of combination therapy albendazole and doxycycline in Angiostrongylus cantonensis-infected mice during early and late treatment. 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 + 25 mg/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. 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. 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.

• Publisher: Elsevier Limited,Chang Gung University
• Subject: Albendazole / Albendazole - pharmacology / Albendazole - therapeutic use / Angiostrongylus cantonensis / Angiostrongylus cantonensis - drug effects / Animals / Anthelmintic agents / Antibiotics / Brain - drug effects / Brain damage / Brain injury / Coordination / Cytokines / Doxycycline / Doxycycline - pharmacology / Doxycycline - therapeutic use / Drug delivery / Drug Therapy, Combination / Drugs / Evaluation / Glial fibrillary acidic protein / Immune response / Immune system / Immunosuppressive agents / Infections / Inflammation / Laboratory animals / Maze learning / Maze Learning - drug effects / Medical research / Meningitis / Mice / Mice, Inbred BALB C / Mice, Inbred C57BL / Mollusks / Original / Proteins / Spatial discrimination learning / Spatial memory / Strongylida Infections - drug therapy / Therapy / Tissues / Tropical diseases / Zoonoses