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Substance P Causes Seizures in Neurocysticercosis

Neurocysticercosis (NCC), a helminth infection of the brain, is a major cause of seizures. The mediators responsible for seizures in NCC are unknown, and their management remains controversial. Substance P (SP) is a neuropeptide produced by neurons, endothelial cells and immunocytes. The current stu...

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Autores principales: Robinson, Prema, Garza, Armandina, Weinstock, Joel, Serpa, Jose A., Goodman, Jerry Clay, Eckols, Kristian T., Firozgary, Bahrom, Tweardy, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276565/
https://www.ncbi.nlm.nih.gov/pubmed/22346746
http://dx.doi.org/10.1371/journal.ppat.1002489
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author Robinson, Prema
Garza, Armandina
Weinstock, Joel
Serpa, Jose A.
Goodman, Jerry Clay
Eckols, Kristian T.
Firozgary, Bahrom
Tweardy, David J.
author_facet Robinson, Prema
Garza, Armandina
Weinstock, Joel
Serpa, Jose A.
Goodman, Jerry Clay
Eckols, Kristian T.
Firozgary, Bahrom
Tweardy, David J.
author_sort Robinson, Prema
collection PubMed
description Neurocysticercosis (NCC), a helminth infection of the brain, is a major cause of seizures. The mediators responsible for seizures in NCC are unknown, and their management remains controversial. Substance P (SP) is a neuropeptide produced by neurons, endothelial cells and immunocytes. The current studies examined the hypothesis that SP mediates seizures in NCC. We demonstrated by immunostaining that 5 of 5 brain biopsies from NCC patients contained substance P (SP)-positive (+) cells adjacent to but not distant from degenerating worms; no SP+ cells were detected in uninfected brains. In a rodent model of NCC, seizures were induced after intrahippocampal injection of SP alone or after injection of extracts of cysticercosis granuloma obtained from infected wild type (WT), but not from infected SP precursor-deficient mice. Seizure activity correlated with SP levels within WT granuloma extracts and was prevented by intrahippocampal pre-injection of SP receptor antagonist. Furthermore, extracts of granulomas from WT mice caused seizures when injected into the hippocampus of WT mice, but not when injected into SP receptor (NK1R) deficient mice. These findings indicate that SP causes seizures in NCC, and, suggests that seizures in NCC in humans may be prevented and/or treated with SP-receptor antagonists.
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spelling pubmed-32765652012-02-15 Substance P Causes Seizures in Neurocysticercosis Robinson, Prema Garza, Armandina Weinstock, Joel Serpa, Jose A. Goodman, Jerry Clay Eckols, Kristian T. Firozgary, Bahrom Tweardy, David J. PLoS Pathog Research Article Neurocysticercosis (NCC), a helminth infection of the brain, is a major cause of seizures. The mediators responsible for seizures in NCC are unknown, and their management remains controversial. Substance P (SP) is a neuropeptide produced by neurons, endothelial cells and immunocytes. The current studies examined the hypothesis that SP mediates seizures in NCC. We demonstrated by immunostaining that 5 of 5 brain biopsies from NCC patients contained substance P (SP)-positive (+) cells adjacent to but not distant from degenerating worms; no SP+ cells were detected in uninfected brains. In a rodent model of NCC, seizures were induced after intrahippocampal injection of SP alone or after injection of extracts of cysticercosis granuloma obtained from infected wild type (WT), but not from infected SP precursor-deficient mice. Seizure activity correlated with SP levels within WT granuloma extracts and was prevented by intrahippocampal pre-injection of SP receptor antagonist. Furthermore, extracts of granulomas from WT mice caused seizures when injected into the hippocampus of WT mice, but not when injected into SP receptor (NK1R) deficient mice. These findings indicate that SP causes seizures in NCC, and, suggests that seizures in NCC in humans may be prevented and/or treated with SP-receptor antagonists. Public Library of Science 2012-02-09 /pmc/articles/PMC3276565/ /pubmed/22346746 http://dx.doi.org/10.1371/journal.ppat.1002489 Text en Robinson et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Robinson, Prema
Garza, Armandina
Weinstock, Joel
Serpa, Jose A.
Goodman, Jerry Clay
Eckols, Kristian T.
Firozgary, Bahrom
Tweardy, David J.
Substance P Causes Seizures in Neurocysticercosis
title Substance P Causes Seizures in Neurocysticercosis
title_full Substance P Causes Seizures in Neurocysticercosis
title_fullStr Substance P Causes Seizures in Neurocysticercosis
title_full_unstemmed Substance P Causes Seizures in Neurocysticercosis
title_short Substance P Causes Seizures in Neurocysticercosis
title_sort substance p causes seizures in neurocysticercosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276565/
https://www.ncbi.nlm.nih.gov/pubmed/22346746
http://dx.doi.org/10.1371/journal.ppat.1002489
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