Disruption of the blood–brain barrier in pigs naturally infected with Taenia solium, untreated and after anthelmintic treatment

Guerra‐Giraldez, Cristina; Marzal, Miguel; Cangalaya, Carla; Balboa, Diana; Orrego, Miguel A.; Paredes, Adriana; Gonzales-Gustavson, Eloy; Arroyo, Gianfranco; Garcı́a, Héctor H.; González, Armando E.; Mahanty, Siddhartha; Nash, Theodore E.

doi:10.1016/j.exppara.2013.05.005

Cited by 23 publications

(42 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests that for precipitation of seizures in cysticercosis, it is likely a necessary condition that the larvae must be directly located within the nervous tissue itself. As our findings suggest, it is still possible that peripheral infection, by driving potential additional disruption to the blood-brain barrier could exacerbate the epileptogenic process in neurocysticercosis (Guerra-Giraldez et al, 2013;Marchi et al, 2007). Taken together our findings contribute to the understanding of neuroimmune responses in the T. crassiceps model of cysticercosis, and more broadly, disease processes in human cysticercosis.…”

Section: Discussionsupporting

confidence: 58%

Peripheral Taenia infection increases immunoglobulins in the central nervous system.

Belle

Lange

Tomes

et al. 2020

Preprint

View full text Add to dashboard Cite

Human cysticercosis is a disease caused by larvae of the cestode Taenia solium. It is the most common cause of adult-acquired epilepsy world-wide where it exacts a debilitating toll on the health and well-being of affected communities. It is commonly assumed that the major symptoms associated with cysticercosis are a result of the direct presence of larvae in the brain. As a result, the possible effect of peripherally located larvae on the central nervous system are not well understood. To address this question, we utilised the Taenia crassiceps intra-peritoneal murine model of cysticercosis, where larvae are restricted to the peritoneal cavity. In this model, previous research has observed behavioural changes in rodents but not the development of seizures. Here we used ELISAs, immunoblotting and the Evans Blue test for blood-brain barrier permeability to explore the central effects of peripheral infection of mice with Taenia crassiceps. We identified high levels of parasite-targeting immunoglobulins in the serum of Taenia crassiceps infected mice. We show that the Taenia crassciceps larvae themselves also contain and release host immunoglobulins over time. Additionally, we describe, for the first time, significantly increased levels of IgG within the hippocampi of infected mice, which are accompanied by changes in blood-brain barrier permeability. However, these Taenia crassiceps induced changes were not accompanied by alterations to the levels of proinflammatory, pro-seizure cytokines in the hippocampus. These findings contribute to the understanding of systemic and neuroimmune responses in the Taenia crassiceps model of cysticercosis, with implications for the pathogenesis of human cysticercosis.

show abstract

Section: Discussionsupporting

confidence: 58%

Peripheral Taenia infection increases immunoglobulins in the central nervous system.

Belle

Lange

Tomes

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The presence of viable brain cysts in our model also represents an advantage for the study of pathogenesis of inflammatory responses following antiparasitic treatment. In comparison with studies of NCC using naturally infected pigs, [13][14][15] our model allows to control variables, such as cyst longevity in the CNS, infection dose, and concurrent CNS infections, which may impact the interpretability of different treatment regimens against NCC.…”

Section: Discussionmentioning

confidence: 99%

“…12 In addition, an animal model with high rates of viable cyst infections in the CNS may allow the control of variables such as infection dose and cyst longevity, especially important in controlled studies for treatment regimens. [13][14][15] A variety of studies have been performed using pigs [16][17][18][19][20] and rodents [21][22][23][24] as NCC animal models, each with their own advantages and disadvantages. We describe a novel experimental porcine NCC model, using ultrasoundguided carotid artery catheterization.…”

Section: Introductionmentioning

confidence: 99%

Carotid Taenia solium Oncosphere Infection: A Novel Porcine Neurocysticercosis Model

Alroy

Arroyo

Gilman

et al. 2018

The American Journal of Tropical Medicine and Hygiene

Self Cite

View full text Add to dashboard Cite

Neurocysticercosis (NCC), the infection of the human central nervous system (CNS) with larval cysts of causes widespread neurological morbidity. Animal models are crucial for studying the pathophysiology and treatment of NCC. Some drawbacks of current NCC models include differences in the pathogenesis of the model and wild-type parasite, low rates of infection efficiency and lack of reproducibility. We describe a novel porcine model that recreates infection in the CNS with high efficiency. Activated oncospheres, either in a high (45,000-50,000) or low (10,000) dose were inoculated in the common carotid artery of 12 pigs by ultrasound-guided catheterization. Following oncosphere injection, either a high (30 mL) or low (1-3 mL) volume of saline flush was also administered. Cyst burden in the CNS was evaluated independently according to oncosphere dose and flush volume. Neurocysticercosis was achieved in 8/12 (66.7%) pigs. Cyst burden in the CNS of pigs was higher in the high versus the low oncosphere dose category (median: 4.5; interquartile ranges [IQR]: 1-8 and median: 1; IQR: 0-4, respectively) and in the high versus the low flush volume category (median 5.5; IQR: 1-8 and median: 1; IQR: 0-2, respectively), although not statistically different. All cysts in the CNS were viable, whereas both viable and degenerated cysts were found in the musculature. Carotid injection of activated oncospheres in pigs is effective in reproducing NCC. Oncosphere entry into the CNS by way of vasculature mimics wild-type infection, and provides a useful alternative for future investigations on the pathogenesis and antiparasitic treatment of NCC.

show abstract

“…The methods employed for treatment, EB injection, treatment and collection of samples have been reported [29]. Briefly, eight heavily infected pigs were treated with a single oral dose of praziquantel (100 mg/kg; 10% Saniquantel, Montana S.A, Peru); four were euthanized at 48 hr (PZQ48) and four were euthanized 120 hr (PZQ120) post treatment.…”

Section: Methodsmentioning

confidence: 99%

Evans Blue Staining Reveals Vascular Leakage Associated with Focal Areas of Host-Parasite Interaction in Brains of Pigs Infected with Taenia solium

et al. 2014

Self Cite

View full text Add to dashboard Cite

Cysticidal drug treatment of viable Taenia solium brain parenchymal cysts leads to an acute pericystic host inflammatory response and blood brain barrier breakdown (BBB), commonly resulting in seizures. Naturally infected pigs, untreated or treated one time with praziquantel were sacrificed at 48 hr and 120 hr following the injection of Evans blue (EB) to assess the effect of treatment on larval parasites and surrounding tissue. Examination of harvested non encapsulated muscle cysts unexpectedly revealed one or more small, focal round region(s) of Evans blue dye infiltration (REBI) on the surface of otherwise non dye-stained muscle cysts. Histopathological analysis of REBI revealed focal areas of eosinophil-rich inflammatory infiltrates that migrated from the capsule into the tegument and internal structures of the parasite. In addition some encapsulated brain cysts, in which the presence of REBI could not be directly assessed, showed histopathology identical to that of the REBI. Muscle cysts with REBI were more frequent in pigs that had received praziquantel (6.6% of 3736 cysts; n = 6 pigs) than in those that were untreated (0.2% of 3172 cysts; n = 2 pigs). Similar results were found in the brain, where 20.7% of 29 cysts showed histopathology identical to muscle REBI cysts in praziquantel-treated pigs compared to the 4.3% of 47 cysts in untreated pigs. Closer examination of REBI infiltrates showed that EB was taken up only by eosinophils, a major component of the cellular infiltrates, which likely explains persistence of EB in the REBI. REBI likely represent early damaging host responses to T. solium cysts and highlight the focal nature of this initial host response and the importance of eosinophils at sites of host-parasite interaction. These findings suggest new avenues for immunomodulation to reduce inflammatory side effects of anthelmintic therapy.

show abstract

Disruption of the blood–brain barrier in pigs naturally infected with Taenia solium, untreated and after anthelmintic treatment

Cited by 23 publications

References 34 publications

Peripheral Taenia infection increases immunoglobulins in the central nervous system.

Peripheral Taenia infection increases immunoglobulins in the central nervous system.

Carotid Taenia solium Oncosphere Infection: A Novel Porcine Neurocysticercosis Model

Evans Blue Staining Reveals Vascular Leakage Associated with Focal Areas of Host-Parasite Interaction in Brains of Pigs Infected with Taenia solium

Contact Info

Product

Resources

About