7,8-Dihydroxyflavone provides neuroprotection and rescues behavioral deficits in Angiostrongylus cantonensis-infected mice by ameliorating synaptic loss.

BACKGROUND

Angiostrongylus cantonensis triggers eosinophilic meningitis and/or eosinophilic meningoencephalitis in humans, potentially causing permanent central nervous system damage. While corticosteroids may ease infection-induced headaches, they prove ineffective against A. cantonensis larvae or neuronal injuries. Conversely, anthelmintics and neuroprotective agents like 7,8-Dihydroxyflavone (7,8-DHF), activating BDNF/TrkB signaling, offer promise.

METHODS

This study aimed to assess neural structure, brain function impairment and recovery, and pathological symptoms and cell death in A. cantonensis-infected C57BL/6 mice before and after treatment with 7,8-DHF or Albendazole alone, and in combination with 7,8-DHF/Albendazole.

RESULTS

All treatment groups effectively mitigated infection-induced weight loss in mice. Those receiving 7,8-DHF or combined treatment displayed significant improvements in motor and balance abilities during the rotarod test. Post-treatment, infected mice showed enhanced spatial learning and memory in the Morris water maze test. Golgi staining revealed that strategies involving 7,8-DHF reduced infection-induced synaptic loss. A. cantonensis infection induced severe inflammatory responses and brain damage in mice. Albendazole alone and the combined 7,8-DHF/Albendazole treatment effectively alleviated inflammation-related pathological phenomena. Analysis of neuronal functional protein expression across different brain regions showed increased presynaptic proteins following 7,8-DHF treatment. Moreover, 7,8-DHF treatment alone or combined with Albendazole prevented brain injury without inducing cell death in infected mice.

CONCLUSION

These findings suggested that 7,8-DHF could confer neuroprotective effects, particularly in mitigating synaptic loss in the presynaptic region, and alleviating behavioral deficits from infection without inducing cell death. We anticipate these results will aid in the treatment of angiostrongyliasis-induced neurological damage.