Substance P causes seizures in neurocysticercosis.
Substance P causes seizures in neurocysticercosis.
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DOI：
10.1371/journal.ppat.1002489
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发表时间：
2012-02
期刊：
影响因子：
6.7
通讯作者：
Tweardy DJ
中科院分区：
文献类型：
--
作者：
Robinson P;Garza A;Weinstock J;Serpa JA;Goodman JC;Eckols KT;Firozgary B;Tweardy DJ
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. Neurocysticercosis (NCC), is a helminth infection of the brain that is caused by Taenia solium. NCC is the major cause of acquired seizures worldwide. Live Taenia solium parasites in the brain of NCC patients are surrounded by little or no inflammation. Seizures are thought to result not from parasitic infection per se, but from the chronic granulomatous host response initiated by dying cysts. Antiparasitic drugs can be used to kill the parasites, but the symptoms may worsen due to the host inflammatory responses being stimulated by the dying parasites. The mediators that are responsible for mediating seizures in NCC are not known; identification of the seizure mediator(s) may lead to prevention/treatment of seizures with specific antagonists. In this important study, we demonstrated that Substance P, a neuropeptide and pain transmitter is responsible for seizures in NCC. These studies have potential implications for treatment and prevention of seizures in the setting of NCC.
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影响因子：
3.1
作者：
Robinson, P;White, AC;Weinstock, J
通讯作者：
Weinstock, J
影响因子：
3.3
作者：
Nalivaiko, E;Michaud, JC;Feltz, P
通讯作者：
Feltz, P
影响因子：
1.3
作者：
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通讯作者：
White, A. Clinton, Jr.
影响因子：
9.9
作者：
DELBRUTTO, OH
通讯作者：
DELBRUTTO, OH
影响因子：
64.8
作者：
Cao, YQ;Mantyh, PW;Basbaum, AI
通讯作者：
Basbaum, AI