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

Abstract

Neurocysticercosis (NCC) is a helminth infection affecting the central nervous system caused by the larval stage (cysticercus) of Taenia solium. Since vascular alteration and blood-brain barrier (BBB) disruption contribute to NCC pathology, it is postulated that angiogenesis could contribute to the pathology of this disease. This study used a rat model for NCC and evaluated the expression of two angiogenic factors called vascular endothelial growth factor (VEGF-A) and fibroblast growth factor (FGF2). Also, two markers for BBB disruption, the endothelial barrier antigen and immunoglobulin G, were evaluated using immunohistochemical and immunofluorescence techniques. Brain vasculature changes, BBB disruption, and overexpression of angiogenesis markers surrounding viable cysts were observed. Both VEGF-A and FGF2 were overexpressed in the tissue surrounding the cysticerci, and VEGF-A was overexpressed in astrocytes. Vessels showed decreased immunoreactivity to endothelial barrier antigen marker and an extensive staining for IgG was found in the tissues surrounding the cysts. Additionally, an endothelial cell tube formation assay using human umbilical vein endothelial cells showed that excretory and secretory antigens of T. solium cysticerci induce the formation of these tubes. This in vitro model supports the hypothesis that angiogenesis in NCC might be caused by the parasite itself, as opposed to the host inflammatory responses alone. In conclusion, brain vasculature changes, BBB disruption, and overexpression of angiogenesis markers surrounding viable cysts were observed. This study also demonstrates that cysticerci excretory-secretory processes alone can stimulate angiogenesis.

Changes in inflammatory gene expression in brain tissue adjacent and distant to a viable cyst in a rat model for neurocysticercosis

“…This contrasts a previous report by our group which showed angiogenesis in NCC-infected brain slices as well as an increase in VEGF-A protein expression surrounding the cyst [ 10 ]. Even though we did not find significantly increased levels of gene expression associated with angiogenesis in this study, it is evident that in the tissue surrounding the cyst, angiogenesis is present and expected [ 10 , 17 ]. Furthermore, we did not observe a parallel relationship between VEGF-A RNA levels in this study and VEGF-A protein levels reported in our previous study.…”

“…Our group has shown in the rat model that changes such as blood-brain-barrier disruption, angiogenic factor overexpression, and axonal swellings occur in the presence of viable cysts [ 10 , 11 ]. Most of these changes have been found and reported in the tissue surrounding the cyst.…”

Recombinant Annexin A2 Administration Improves Neurological Outcomes After Traumatic Brain Injury in Mice

“…For example, VEGF-A and its receptors initiate the formation of immature vessels, while Ang1 and other molecules play essential roles in regulating maturation, stabilization, and remodeling of vessels ( Yancopoulos et al, 1998 ). Pro-angiogenetic factors VEGF-A/VEGFR-2 plays a key role in enhancing angiogenesis during the recovery phase after TBI via activating multiple pro-angiogenetic signaling pathways ( Carmen-Orozco et al, 2019 ). Angiopoietin/Tie2 axis mediates neuroprotection and BBB stability in juvenile mice after TBI ( Brickler et al, 2018 ).…”

The excretory/secretory products of fifth-stage larval Angiostrongylus cantonensis induces autophagy via the Sonic hedgehog pathway in mouse brain astrocytes

“…CNS and induce brain damage via BBB breakdown [55][56][57][58][59]. Research on A. cantonensis has also demonstrated that BBB disruption occurs in mice after A. cantonensis infection [60].…”