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

Abstract

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.

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

“…Angiogenesis and disruption of the BBB could contribute to the pathogenesis of NCC in humans (Restrepo et al, ). Vascular alteration, occlusion, and thickness of vessels have been reported in postmortem samples of patients (Del Brutto, ), while BBB disruption in pigs with NCC has also been observed (Marzal et al, ). Studies have shown that BBB disruption and extravasation of serum proteins into the cerebral parenchyma promotes epileptogenesis (Bar‐Klein et al, ; Ivens et al, ), a major symptom of NCC.…”

“…The study of biopsies in NCC patients and the use of animal models have established that the pathology varies according to the number, location, and viability of the cysticerci (Chandy et al, ; Guerra‐Giraldez et al, ; Marzal et al, ). The use of imaging techniques such as magnetic resonance imaging and computerized tomography have allowed for the identification of inflammatory reactions and the grade of cysticerci degeneration (Del Brutto, ; Shetty, Avabratha, & Rai, ).…”

“…However, such techniques, do not provide information about either physiological or molecular changes in the disease. Pathological characteristics of NCC in humans and pigs include the presence of inflammatory cells, fibrosis, gliosis, and blood–brain barrier (BBB) disruption surrounding the parasite (Alvarez, Londoño et al, ; Marzal et al, ; Restrepo et al, ; Sikasunge, Johansen, Phiri, Willingham, & Leifsson, ).…”

Antiparasitic treatment of neurocysticercosis - The effect of cyst destruction in seizure evolution

“…Initially, the parasitic cysts establish and modulate the immune response, with minimal pericystic inflammation and focal reactive gliosis. 52,53 Once the host’s immune system breaks the immune evasion defenses of the cyst, a focal inflammatory response involving cytokine production and cellular infiltration initiates the process of destruction of the cyst, 53–55 with an evident inflammatory reaction involving BBB rupture and perilesional edema. Then the parasite is destroyed and the inflammatory process subsides, with eventual resolution on neuroimaging, or leaving a residual calcification.…”

Norrin Protected Blood–Brain Barrier Via Frizzled-4/β-Catenin Pathway After Subarachnoid Hemorrhage in Rats

“…Then the brains were removed to be prepared for coronal brain sections (10 μm) as same as Immunofluorescence Staining. And red autofluorescence of Evans Blue was observed on the slides using excitation and emission filters for rhodamine fluorescence 15 (Olympus OX51, Tokyo, Japan).…”