Post-treatment Vascular Leakage and Inflammatory Responses around Brain Cysts in Porcine Neurocysticercosis

Abstract

Cysticidal treatment of neurocysticercosis, an infection of humans and pig brains with Taenia solium, results in an early inflammatory response directed to cysts causing seizures and focal neurological manifestations. Treatment-induced pericystic inflammation and its association with blood brain barrier (BBB) dysfunction, as determined by Evans blue (EB) extravasation, was studied in infected untreated and anthelmintic-treated pigs. We compared the magnitude and extent of the pericystic inflammation, presence of EB-stained capsules, the level of damage to the parasite, expression of genes for proinflammatory and regulatory cytokines, chemokines, and tissue remodeling by quantitative PCR assays between treated and untreated infected pigs and between EB-stained (blue) and non stained (clear) cysts. Inflammatory scores were higher in pericystic tissues from EB-stained cysts compared to clear cysts from untreated pigs and also from anthelmintic-treated pigs 48 hr and 120 hr after treatment. The degree of inflammation correlated with the severity of cyst wall damage and both increased significantly at 120 hours. Expression levels of the proinflammatory genes for IL-6, IFN-γ, TNF-α were higher in EB-stained cysts compared to clear cysts and unaffected brain tissues, and were generally highest at 120 hr. Additionally, expression of some markers of immunoregulatory activity (IL-10, IL-2Rα) were decreased in EB-stained capsules. An increase in other markers for regulatory T cells (CTLA4, FoxP3) was found, as well as significant increases in expression of two metalloproteases, MMP1 and MMP2 at 48 hr and 120 hr post-treatment. We conclude that the increase in severity of the inflammation caused by treatment is accompanied by both a proinflammatory and a complex regulatory response, largely limited to pericystic tissues with compromised vascular integrity. Because treatment induced inflammation occurs in porcine NCC similar to that in human cases, this model can be used to investigate mechanisms involved in host damaging inflammatory responses and agents or modalities that may control damaging post treatment inflammation.

Recent advancements and new perspectives in animal models for Neurocysticercosis immunopathogenesis

“…Naturally infected pig as a study model is gradually becoming more popular, as this model is easily available across all endemic areas and the infected pigs can be identified easily based on clinical signs together with either tongue or neck muscle examinations . We have extensively used this model to study immunopathology of disease and the effect of cysticidal drugs as this model provides good number of cysts of different stages .…”

“…We found Th1 response associated with cyst in case of albendazole‐only treatment and mixed Th1 and Th2 responses when treated with albendazole and steroid. Researchers from The Cysticercosis Working Group in Peru and National Institutes of Health, USA (NIH), have also used this model to study the effect of praziquantel treatment‐induced pericystic inflammation and its association with blood‐brain barrier (BBB) . They noticed disruption of BBB and enhanced inflammation after 120 hours of drug treatment.…”

“…Probably, as suggested by authors, reducing the time between infection, treatment and necropsy will allow getting cysticerci of different stages in order to be able to evaluate treatment/drug efficacy. 12 Naturally infected pig as a study model is gradually becoming more popular, 12,13,[15][16][17][18]22,23 as this model is easily available across all endemic areas and the infected pigs can be identified easily based on clinical signs 18 together with either tongue or neck muscle examinations. 14 We have extensively used this model to study immunopathology of disease and the effect of cysticidal drugs as this model provides good number of cysts of different stages.…”

“…Health, USA (NIH), have also used this model to study the effect of praziquantel treatment-induced pericystic inflammation and its association with blood-brain barrier (BBB). 22 They noticed disruption of BBB and enhanced inflammation after 120 hours of drug treatment. They also observed that increased pericystic inflammation (IL-6, TNFα, IFNγ) is co-related with increased damage to the cysticerci cell wall and disruption of BBB.…”

A Case of Neurocysticercosis Clinically Mimicking Epilepsy: Report from Remote Hilly Area of Bangladesh

“…The adult tape worm releases cysticerci which can disseminate to different parts of the body. Cysticerci infection of tissues of the central nervous system causes NCC [11][12] .…”