Co-Therapy of Albendazole and Dexamethasone Reduces Pathological Changes in the Cerebral Parenchyma of Th-1 and Th-2 Dominant Mice Heavily Infected with Angiostrongylus cantonensis: Histopathological and RNA-seq Analyses

Biomolecules. 2021 Apr 6;11(4):536. doi: 10.3390/biom11040536.

Abstract

Administration of albendazole alone was not very suitable for the treatment of cerebral angiostrongyliasis. This study was designed to evaluate the effects of the co-therapy of this drug and dexamethasone in Th-1 and Th-2 dominant mice infected with Angiostrongylus cantonensis. Each of BALB/c and C57BL/6 mice infected with 50 A. cantonensis third-stage larvae were administered albendazole (10 mg/kg/day) alone, dexamethasone (0.5 mg/kg/day) alone, or co-therapy of the two drugs from day 7 or 14 post-infection for 7 or 14 days. After sacrifice, coronal slices were prepared from five brain regions and stained with hematoxylin and eosin. Eight pathological changes were employed to determine the therapeutic effectiveness using a scoring system. RNA-seq analysis was performed to confirm the histopathological findings. The infected BALB/c and C57BL/6 mice had similar patterns in the pathological changes. Meningitis, hemorrhage, size of worms, and encephalitis in the cerebral parenchyma were slighter in the mice treated with co-therapy than the remaining groups. Mice treated from day 14 had more severe changes than those from day 7. The histopathological findings were found to be consistent to immune responses determined by RNA-seq analysis. Co-therapy was determined to reduce pathological changes after administration to mice infected with A. cantonensis.

Keywords: Angiostrongylus cantonensis; RNA-seq; albendazole; dexamethasone; histopathology; pathological changes; scoring.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albendazole / therapeutic use*
  • Angiostrongylus cantonensis / pathogenicity*
  • Animals
  • Brain / metabolism
  • Brain / pathology*
  • Dexamethasone / therapeutic use*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • RNA / chemistry
  • RNA / metabolism
  • Sequence Analysis, RNA
  • Strongylida Infections / drug therapy*
  • Strongylida Infections / parasitology
  • Strongylida Infections / pathology
  • Th1 Cells / cytology
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • RNA
  • Dexamethasone
  • Albendazole

Supplementary concepts

  • Angiostrongyliasis