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In silico Transcriptomics-based Drug Repositioning in a rat model identifies Vorinostat as a candidate to modulate neuroinflammation in Neurocysticercosis

ABSTRACT: Neurocysticercosis (NCC) is a major cause of epilepsy and neurological symptoms in low- and middle-income countries. Although antiparasitic treatment targets the parasite, it often fails to fully resolve symptoms and can exacerbate brain tissue damage. Using a rat model of NCC and transcriptomic profiling, we assessed the effects of infection and treatment on brain gene expression to uncover disease mechanisms and identify therapeutic candidates. We analyzed transcriptomic profiles at two stages of infection (4- and 6-month post-infection (MPI)), and after treatment at 6 MPI (6 MPI +T). At 6 MPI, fewer immune-related genes and pathways were enriched compared to 4 MPI, likely due to MAPK pathway repression, but immune activation increased significantly after treatment, possibly due to cyst degeneration. Drug repositioning identified 30 candidate drugs. Among them, vorinostat emerged as the most promising, enriched across all stages and predicted to cross the blood–brain barrier, with potential to reduce neuroinflammation and neurodegeneration.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE306561 | GEO | 2026/08/26

REPOSITORIES: GEO

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Project description:Neurocysticercosis, caused by the establishment of Taenia solium larvae in the central nervous system, is a leading cause of acquired epilepsy and neurological morbidity in endemic regions. Viable cysticerci can persist in the brain for years with minimal inflammation, whereas parasite degeneration, either spontaneous or induced by antiparasitic treatment, triggers intense inflammatory and vascular responses. Despite the clinical relevance of this transition, the host transcriptional changes associated with viable infection and early post-treatment lesions remain poorly understood. We performed the first bulk RNA sequencing analysis of brain tissue from experimentally infected pigs, a physiologically relevant model of human neurocysticercosis. We compared transcriptional profiles from uninfected controls (n=3), infected untreated pigs with viable clear-capsule cysts (n=6), and infected pigs treated with albendazole plus praziquantel with disrupted blue-capsule lesions (n=3). Differential expression and pathway enrichment analyses were used to characterise host responses associated with infection and treatment. Neurocysticercosis infection was associated with altered expression of genes involved in immune activation, together with reduced vascular- and endothelial-associated signalling. In contrast, anthelmintic treatment was associated with coordinated inflammatory and endothelial activation, including cell adhesion molecule pathways, extracellular matrix remodelling, and transcriptional features consistent with active blood-brain barrier remodelling in a disrupted lesion state. Integrated pathway analysis showed that infection and treatment shared immune activation features but diverged in MAPK, vascular and endothelial programmes. These findings show that viable and post-treatment lesions are associated with distinct host transcriptional programmes involving immune regulation, endothelial activation and barrier-associated tissue remodelling. By defining these lesion-associated signatures, this study provides a framework for understanding parasite persistence, inflammation and disease progression in porcine neurocysticercosis.

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In silico Transcriptomics-based Drug Repositioning in a rat model identifies Vorinostat as a candidate to modulate neuroinflammation in Neurocysticercosis

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