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.
|Number of pages||12|
|Journal||Journal of Neuroscience Research|
|State||Published - Feb 2019|
Bibliographical noteFunding Information:
The research activities were supported by: National Institutes of Health grant 5D43TW006581 (Infectious Diseases Training Program in Peru) (R.H.G.), National Institutes of Health grant FIC/NIH D43 TW001140, INNOVATE PERU N-135 PNICP-PIAP 2015, CIENCIACTIVA 118-2015-FONDECYT. We would like to thank Cesar Quispe, Francisco Ancajima, Emma Carter, Jemima Morales, Ana Delgado, Gino Castillo, Izabo Guillen and Lizbeth Fustamante as part of the Cysticercosis Working Group in Peru.
2012). Evans blue staining demonstrates protein extravasation, The research activities were supported by: National Institutes whereas EBA is a group of different proteins with an unclear role of Health grant 5D43TW006581 (Infectious Diseases Training in BBB maintenance. EBA proteins down regulation has been cor-Program in Peru) (R.H.G.), National Institutes of Health grant related with BBB dysfunction in different models and diseases. FIC/NIH D43 TW001140, INNOVATE PERU N‐135 PNICP‐ Even though we tested fibrinogen extravasation here, its staining PIAP 2015, CIENCIACTIVA 118‐2015‐FONDECYT. We would indicates that it is sparsely present in the fibrotic tissue, possibly like to thank Cesar Quispe, Francisco Ancajima, Emma Carter, because there is not enough BBB dysfunction at this level of the Jemima Morales, Ana Delgado, Gino Castillo, Izabo Guillen disease to allow large proteins such as fibrinogen (340 KDa) to move and Lizbeth Fustamante as part of the Cysticercosis Working across the BBB and into the brain parenchyma (Wilhelm, NyD뼄q‐TD? thG, roup in Peru. Suciu, Hermenean, & Krizbai, 2016). In parenchymal and corticomeningeal cysts, our results demon- strated a greater expression of angiogenic markers (VEGF‐A and FGF2) in comparison to the control regions, as well as increases in IgG abundance and number of vessels that are not immunoreactive to EBA. These findings suggest that parenchymal and corticomeningeal cysts have a more intense cellular response compared to ventricular cysts. This may be due to the close contact between the parasite and brain tissue, where cells are more susceptible to tissue injury. The BBB of ventricular cysts was less compromised in comparison to pa- renchymal and corticomeningeal cysts, possibly due to the fact that ependymal cells protect the subventricular zone as part of the cere- broventricular barrier (Del Bigio, 2010). Additionally, the presence of cerebrospinal fluid could cause parasite antigens to be diluted, which, in turn, could prevent an immune response from being elic- ited around the ventricles (Lun, Monuki, & Lehtinen, 2015; Xie et al., 2013). Lastly, host‐parasite physical contact could mediate injuries in corticomeningeal and parenchymal cysts, but not in ventricular cysts.
© 2018 Wiley Periodicals, Inc.
- BBB disruption
- T. solium