Inflammation Caused by Praziquantel Treatment Depends on the Location of the Taenia solium Cysticercus in Porcine Neurocysticercosis

Abstract

BackgroundNeurocysticercosis (NCC), infection of the central nervous system by Taenia solium cysticerci, is a pleomorphic disease. Inflammation around cysticerci is the major cause of disease but is variably present. One factor modulating the inflammatory responses may be the location and characteristics of the brain tissue adjacent to cysticerci. We analyzed and compared the inflammatory responses to cysticerci located in the parenchyma to those in the meninges or cysticerci partially in contact with both the parenchyma and the meninges (corticomeningeal).Methodology/Principal FindingsHistological specimens of brain cysticerci (n = 196) from 11 pigs naturally infected with Taenia solium cysticerci were used. Four pigs were sacrificed after 2 days and four after 5 days of a single dose of praziquantel; 3 pigs did not receive treatment. All pigs were intravenously injected with Evans Blue to assess disruption of the blood-brain barrier. The degree of inflammation was estimated by use of a histological score (ISC) based on the extent of the inflammation in the pericystic areas as assessed in an image composed of several photomicrographs taken at 40X amplification. Parenchymal cysticerci provoked a significantly greater level of pericystic inflammation (higher ISC) after antiparasitic treatment compared to meningeal and corticomeningeal cysticerci. ISC of meningeal cysticerci was not significantly affected by treatment. In corticomeningeal cysticerci, the increase in ISC score was correlated to the extent of the cysticercus adjacent to the brain parenchyma. Disruption of the blood-brain barrier was associated with treatment only in parenchymal tissue.SignificanceInflammatory response to cysticerci located in the meninges was significantly decreased compared to parenchymal cysticerci. The suboptimal inflammatory response to cysticidal drugs may be the reason subarachnoid NCC is generally refractory to treatment compared to parenchymal NCC.

Blood–brain barrier disruption and angiogenesis in a rat model for neurocysticercosis

“…6 images of the tissue closely surrounding the cyst were acquired. Cysticerci were classified according to Cangalaya et al () and included parenchymal, corticomeningeal, and ventricular cysts. Meningeal cysticerci were not considered because they frequently detach during tissue processing.…”

Histopathologic aspects of experimental cysticercosis and in situ cytokines profile in C57BL/6 mice

“…However, in our study, the localization of the parasite within the brain was mainly in the meningocortical region, differing from the previously-cited study. This difference is important in the description of the host response to the parasite, due to the fact that parenchymal NCC is associated with seizures and focal neurological signs and is the form that presents with greater inflammation when treated 26 . The human extraparenchymal NCC is associated with high mortality rates due to the increase in intracranial pressure 6 .…”

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 .…”

“…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.…”

“…They found that the inflammatory response to cysticerci located in the meninges was significantly decreased compared to cyst located in brain parenchyma. 23 Although they also cautioned about the interpretation of results coming from this model as the parasite burden in naturally infected swine is much higher and the longevity of infection is shorter in pigs, 22 the heavy burden of parasite antigens may also have a dampening effect on inflammatory responses as observed in other helminthic infections.…”