Substance P Causes Seizures in Neurocysticercosis

Robinson, Prema; Garza, Armandina; Weinstock, Joel V.; Serpa, José A.; Goodman, J. Clay; Eckols, Kristian T.; Firozgary, Bahrom; Tweardy, David J.

doi:10.1371/journal.ppat.1002489

Cited by 56 publications

(48 citation statements)

References 34 publications

(31 reference statements)

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“…As mentioned, SP is present in the brain of NCC patients and co-localizes with areas of inflammation adjacent to degenerating worms 24 . Studies using T. crassiceps infected mice showed that, similar to T. solium infection in humans, cysts cause little or no inflammation, while dead or dying parasites initiate a granulomatous reaction.…”

Section: Nk1r Antagonists and Cns-invasive Parasitesmentioning

confidence: 77%

“…Therefore, in a mouse model of NCC, pretreatment with aprepitant resulted in complete abrogation of seizure activity. These findings suggest that NK1R antagonists may be used to prevent and/or treat seizures in NCC in humans and, perhaps, function as an adjuvant or replacement for the treatment of these seizures with antiepileptic drugs 24 .…”

Section: Nk1r Antagonists and Cns-invasive Parasitesmentioning

confidence: 93%

“…It has been linked to the induction of seizures in a rodent model of neurocysticercosis (NCC), caused by the helminth Taenia crassiceps 24 . SP was also implicated in the development of post-treatment inflammatory encephalopathy (PTRE) in a murine model of Trypanosoma brucei infection.…”

Section: Neuroinflammation and Substance Pmentioning

confidence: 99%

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Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

Martínez

Philipp

2016

J Neurol Neuromedicine

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This review addresses the role that substance P (SP) and its preferred receptor neurokinin-1 (NK1R) play in neuroinflammation associated with select bacterial, viral, parasitic, and neurodegenerative diseases of the central nervous system. The SP/NK1R complex is a key player in the interaction between the immune and nervous systems. A common effect of this interaction is inflammation. For this reason and because of the predominance in the human brain of the NK1R, its antagonists are attractive potential therapeutic agents. Preventing the deleterious effects of SP through the use of NK1R antagonists has been shown to be a promising therapeutic strategy, as these antagonists are selective, potent, and safe. Here we evaluate their utility in the treatment of different neuroinfectious and neuroinflammatory diseases, as a novel approach to clinical management of CNS inflammation.

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Section: Nk1r Antagonists and Cns-invasive Parasitesmentioning

confidence: 77%

Section: Nk1r Antagonists and Cns-invasive Parasitesmentioning

confidence: 93%

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Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

Martínez

Philipp

2016

J Neurol Neuromedicine

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“…The data suggest that these tachykinins are critical for the control of the excitability, the seizures, and the vulnerability of the hippocampus (Liu et al 1999). Furthermore, in a rodent model of neurocysticercosis (NCC), it was reported that seizures were induced after intrahippocampal injection of SP alone or extracts of cysticercosis granuloma obtained from infected wild type (WT), but not from infected SP precursor-deficient mice (Robinson et al 2012). Seizure activity was correlated with SP levels within WT granuloma extracts and was prevented by intrahippocampal preinjection of NK-1 receptor antagonists (aprepitant) ( Table 1).…”

Section: Seizurementioning

confidence: 99%

Involvement of substance P and the NK-1 receptor in human pathology

2014

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The peptide substance P (SP) shows a widespread distribution in both the central and peripheral nervous systems, but it is also present in cells not belonging to the nervous system (immune cells, liver, lung, placenta, etc.). SP is located in all body fluids, such as blood, cerebrospinal fluid, breast milk, etc. i.e. it is ubiquitous in human body. After binding to the neurokinin-1 (NK-1) receptor, SP regulates many pathophysiological functions in the central nervous system, such as emotional behavior, stress, depression, anxiety, emesis, vomiting, migraine, alcohol addiction, seizures and neurodegeneration. SP has been also implicated in pain, inflammation, hepatitis, hepatotoxicity, cholestasis, pruritus, myocarditis, bronchiolitis, abortus, bacteria and viral infection (e.g., HIV infection) and it plays an important role in cancer (e.g., tumor cell proliferation, antiapoptotic effects in tumor cells, angiogenesis, migration of tumor cells for invasion, infiltration and metastasis). This means that the SP/NK-1 receptor system is involved in the molecular bases of many human pathologies. Thus, knowledge of this system is the key for a better understanding and hence a better management of many human diseases. In this review, we update the involvement of the SP/NK-1 receptor system in the physiopathology of the above-mentioned pathologies and we suggest valuable future therapeutic interventions involving the use of NK-1 receptor antagonists, particularly in the treatment of emesis, depression, cancer, neural degeneration, inflammatory bowel disease, viral infection and pruritus, in which that system is upregulated.

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“…Furthermore, the involvement of substance P in other types of seizures, e.g. seizures in neurocysticercosis has also been firmly established [165]. The mechanisms of the proconvulsant effect of substance P are not known yet.…”

Section: Substance Pmentioning

confidence: 99%

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

Dobolyi¹,

Kékesi²,

Juhász³

et al. 2014

CMC

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Neuropeptides are signaling molecules participating in the modulation of synaptic transmission. Neuropeptides are stored in dense core synaptic vesicles, the release of which requires profound excitation. Only in the extracellular space, neuropeptides act on G-protein coupled receptors to exert a relatively slow action both pre-and postsynaptically. Consequently, neuropeptide modulators are ideal candidates to influence epileptic tissue overexcited during seizures. Indeed, a number of neuropeptides have been implicated in epilepsy and many of them are considered to have endogenous neuroprotective actions. Neuropeptides, present in the hippocampus, the most frequent focus of seizures in temporal lobe epilepsy, received the largest attention as potential anti-epileptic substances. Hippocampal neuropeptides, somatostatin, neuropeptide Y, galanin, dynorphin, enkephalin, substance P, cholecystokinin, vasoactive intestinal polypeptide, and some neuropeptides, which are also hormones such as ghrelin, angiotensins, corticotropin-releasing hormone, adrenocorticotropin, thyrotropin-releasing hormone, oxytocin and vasopressin involved in epilepsy are discussed in the review article. Oral application of neuropeptides as drugs is typically not efficient because of low bioavailability: rapid degradation and insufficient penetration through the blood-brain barrier. Recent progress in the development of non-peptide agonists and antagonists of neuropeptide receptors as well as gene therapeutic approaches leading to the local production of neuropeptides within the central nervous system will also be discussed.

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Substance P Causes Seizures in Neurocysticercosis

Cited by 56 publications

References 34 publications

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

Substance P and Antagonists of the Neurokinin-1 Receptor in Neuroinflammation Associated with Infectious and Neurodegenerative Diseases of the Central Nervous System

Involvement of substance P and the NK-1 receptor in human pathology

Receptors of Peptides as Therapeutic Targets in Epilepsy Research

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