Clofazimine against cerebral toxoplasmosis in diabetic and dexamethasone-immunosuppressed mice: ultrastructural and semiquantitative transmission electron microscopic study

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Fahmy M.-E.A.; Abdel-Aal A.A.; Hassan S.I.; Shalaby M.A.; Esmat M.

Journal: BMC Neuroscience

Publisher: BioMed Central Ltd

Publication Date: 3 June 2026

Volume / Issue: Volume 27 / Issue 1

Article No.: 22

ISSN: 14712202

DOI: 10.1186/s12868-026-01008-3

Scopus: View on Scopus

PubMed: 42237095

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access


Authors and Affiliations

Fahmy M.-E.A., Medical Parasitology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Abdel-Aal A.A., Department of Medical Parasitology, Faculty of Medicine, Cairo University, Cairo, Egypt, Department of Postgraduate Studies & Scientific Research, Armed Forces College of Medicine (AFCM), Cairo, Egypt; Hassan S.I., Medical Parasitology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Shalaby M.A., Medical Parasitology Department, Theodor Bilharz Research Institute (TBRI), Giza, Egypt; Esmat M., Department of Medical Parasitology, Faculty of Medicine, Misr University for Science and Technology, 6th October City, Egypt


Abstract

Cerebral toxoplasmosis is a common opportunistic parasitic infection of the CNS caused by the Toxoplasma gondii parasite. Host immunosuppression can affect disease outcomes. To explore the changes in the cerebral cortical ultrastructure accompanying the infection in different immune-altered models and to find an effective treatment against the infection, we tested the possible therapeutic effect of clofazimine (CFZ) (the FDA-approved antimycobacterial drug) against the infection using 60 male CD1 Swiss Albino mice divided into 6 groups: 3 dexamethasone (DEX)- treated groups (DEX-only, DEX-infected, and DEX-infected-treated), and 3 streptozotocin (STZ)-induced type 1 diabetic groups (STZ-only, STZ-infected, STZ-infected-treated). The worst ultrastructural changes were observed in the diabetic and diabetic-infected groups, characterized by a significant increase in neuronal apoptotic and necrotic nuclei (P < 0.05) and changes in the numbers and structure of glial cells compared to the DEX and DEX-infected groups. CFZ (at a dose of 10 mg/kg/day for 3 days starting on 45th day post infection) significantly improved cortical neuronal ultrastructural changes in both models (P < 0.05), reduced microglial numbers, increased astrocyte numbers, and restored brain capillary integrity and axonal growth, in addition to significantly reducing mature cyst numbers in both models (P < 0.05). However, the drug didn’t reduce the number of atrophic and necrotic cysts in the infected-treated groups. So, in our study, CFZ showed preclinical promise in treating experimental cerebral toxoplasmosis and reducing the parasitic cyst burden, highlighting the adverse impact of the host’s altered immune status on brain tissue and the course of the infection, especially in diabetes. © The Author(s) 2026.


Keywords

Cerebral toxoplasmosis; Clofazimine; DEX; Diabetes; Ultrastructure; Animals; Brain; Cerebral Cortex; Dexamethasone; Diabetes Mellitus, Experimental; Disease Models, Animal; Male; Mice; Microscopy, Electron, Transmission; Neurons; Toxoplasmosis, Cerebral; animal experiment; animal model; animal tissue; apoptosis; Article; astrocyte; axon; brain capillary; brain tissue; cell count; disease severity; drug effect; glia cell; immunosuppressive treatment; insulin dependent diabetes mellitus; microglia; mortality rate; mouse; nonhuman; pyramidal nerve cell; streptozotocin-induced diabetes mellitus; Swiss Webster mouse; transmission electron microscopy; animal; brain cortex; complication; disease model; drug therapy; experimental diabetes mellitus; immunology; nerve cell; pathology


Citation Information

Scopus Citations: 0


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