Substance P Causes Seizures in Neurocysticercosis

PLoS Pathogens

David J. Tweardy¹  Jose A. Serpa¹  Armandina Garza¹  Prema Robinson¹  Bahrom Firozgary¹  Kristian T. Eckols¹  Jerry Clay Goodman²  Joel Weinstock³ 

[1] Department of Medicine, Baylor College of Medicine, Houston, Texas, United States of America;Department of Pathology, Baylor College of Medicine, Houston, Texas, United States of America;Division of Gastroenterology, Tufts New England Medical Center, Boston, Massachusetts, United States of America

关键词: Granulomas;    Rats;    Mice;    Electroencephalography;    Hippocampus;    Inflammation;    Parasitic diseases;    Mouse models;   

DOI  :  10.1371/journal.ppat.1002489

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY