Substance P Causes Seizures in Neurocysticercosis

English version České info

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.

Vyšlo v časopise: Substance P Causes Seizures in Neurocysticercosis. PLoS Pathog 8(2): e32767. doi:10.1371/journal.ppat.1002489
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002489

Souhrn

Zdroje

1. SinghiP 2011 Infectious causes of seizures and epilepsy in the developing world. Dev Med Child Neurol 53 600 609

2. ShanderaWXKassJS 2006 Neurocysticercosis: current knowledge and advances. Curr Neurol Neurosci Rep 6 453 459

3. CruzMESchantzPMCruzIEspinosaPPreuxPM 1999 Epilepsy and neurocysticercosis in an Andean community. Int J Epidemiol 28 799 803

4. MedinaMTRosasERubio-DonnadieuFSoteloJ 1990 Neurocysticercosis as the main cause of late-onset epilepsy in Mexico. Arch Intern Med 150 325 327

5. WhiteACJr 2000 Neurocysticercosis: updates on epidemiology, pathogenesis, diagnosis, and management. Annu Rev Med 51 187 206

6. MurthyJMYangalaR 1998 Etiological spectrum of symptomatic localization related epilepsies: a study from South India. J Neurol Sci 158 65 70

7. OngSTalanDAMoranGJMowerWNewdowM 2002 Neurocysticercosis in radiographically imaged seizure patients in U.S. emergency departments. Emerg Infect Dis 8 608 613

8. CuetterACGarcia-BobadillaJGuerraLGMartinezFMKaimB 1997 Neurocysticercosis: focus on intraventricular disease. Clin Infect Dis 24 157 164

9. EscobarA 1983 Cysticercosis of the central nervous system. PalaciosERodriguez-CarbajalJTaverasJ Springfield, III: Charles C Thomas, Publisher

10. GutierrezY 1990 Diagnostic pathology of parasitic infection with clinical correlation Philadelphia Lea and Febiger 432 459

11. Riduara SanzC 1987 Host response in childhood neurocysticercosis. Child's Nerv Syst 3 206 207

12. WeinstockJVBlumAWalderJWalderR 1988 Eosinophils from granulomas in murine schistosomiasis mansoni produce substance P. J Immunol 141 961 966

13. MaggiCA 1997 The effects of tachykinins on inflammatory and immune cells. Regul Pept 70 75 90

14. HoWZLaiJPZhuXHUvaydovaMDouglasSD 1997 Human monocytes and macrophages express substance P and neurokinin-1 receptor. J Immunol 159 5654 5660

15. CookGAElliottDMetwaliABlumAMSandorM 1994 Molecular evidence that granuloma T lymphocytes in murine schistosomiasis mansoni express an authentic substance P (NK-1) receptor. J Immunol 152 1830 1835

16. GoodeTO'ConnellJSterniniCAntonPWongH 1998 Substance P (neurokinin-1) receptor is a marker of human mucosal but not peripheral mononuclear cells: molecular quantitation and localization. J Immunol 161 2232 2240

17. HonorePRogersSDSchweiMJSalak-JohnsonJLLugerNM 2000 Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience 98 585 598

18. LiuHMazaratiAMKatsumoriHSankarRWasterlainCG 1999 Substance P is expressed in hippocampal principal neurons during status epilepticus and plays a critical role in the maintenance of status epilepticus. Proc Natl Acad Sci U S A 96 5286 5291

19. LiuHCaoYBasbaumAIMazaratiAMSankarR 1999 Resistance to excitotoxin-induced seizures and neuronal death in mice lacking the preprotachykinin A gene. Proc Natl Acad Sci U S A 96 12096 12101

20. RobinsonPAtmarRLLewisDEWhiteACJr 1997 Granuloma cytokines in murine cysticercosis. Infect Immun 65 2925 2931

21. RobinsonPWhiteACLewisDEThornbyJDavidE 2002 Sequential expression of the neuropeptides substance P and somatostatin in granulomas associated with murine cysticercosis. Infect Immun 70 4534 4538

22. StringerMLWhiteACJrRobinsonP 2003 Epileptogenic activity of granulomas associated with murine cysticercosis. Exp Neurol 183 532 536

23. PatilSRobinsonPActorJKBaigSWhiteACJr 2006 Proinflammatory cytokines in granulomas associated with murine cysticercosis are not the cause of seizures. J Parasitol 92 738 741

24. KunzJKalinnaBWatschkeVGeyerE 1989 Taenia crassiceps metacestode vesicular fluid antigens shared with the Taenia solium larval stage and reactive with serum antibodies from patients with neurocysticercosis. Zentralbl Bakteriol 271 510 520

25. LarraldeCMontoyaRMSoteloJHayungaJSciuttoE 1990 Murine T. crassiceps antigens in immunodiagnosis of T. solium human neurocysticercosis, T. saginata bovine cysticercosis, and human E. granulosus hydatidosis. Bull Soc Fr Parasitol 8 S8B

26. VillaOKuhnR 1991 Antigenic and immunogenic analysis of Taenia crassiceps and Taenia solium using sera from their natural intermediate hosts. ASB Bull 39 99 105

27. SciuttoEFragosoGBacaMDe la CruzVLemusL 1995 Depressed T-cell proliferation associated with susceptibility to experimental Taenia crassiceps infection. Infect Immun 63 2277 2281

28. VezzaniABalossoSRavizzaT 2008 The role of cytokines in the pathophysiology of epilepsy. Brain Behav Immun 22 797 803

29. RaoRSPrakashAMedhiB 2009 Role of different cytokines and seizure susceptibility: a new dimension towards epilepsy research. Indian J Exp Biol 47 625 634

30. NalivaikoEMichaudJCSoubriePLe FurGFeltzP 1997 Tachykinin neurokinin-1 and neurokinin-3 receptor-mediated responses in guinea-pig substantia nigra: an in vitro electrophysiological study. Neuroscience 78 745 757

31. Del BruttoOHSantibanezRNoboaCAAguirreRDiazE 1992 Epilepsy due to neurocysticercosis: analysis of 203 patients. Neurology 42 389 392

32. Del BruttoOH 1994 Prognostic factors for seizure recurrence after withdrawal of antiepileptic drugs in patients with neurocysticercosis. Neurology 44 1706 1709

33. NashTEPretellEJLescanoAGBustosJAGilmanRH 2008 Perilesional brain oedema and seizure activity in patients with calcified neurocysticercosis: a prospective cohort and nested case-control study. Lancet Neurol 7 1099 1105

34. NashTEPatronasNJ 1999 Edema associated with calcified lesions in neurocysticercosis. Neurology 53 777 781

35. NashTEPretellEJGarciaHH 2001 Calcified cysticerci provoke perilesional edema and seizures. Clin Infect Dis 33 1649 1653

36. CaoYQMantyhPWCarlsonEJGillespieAMEpsteinCJ 1998 Primary afferent tachykinins are required to experience moderate to intense pain. Nature 392 390 394

37. BozicCRLuBHopkenUEGerardCGerardNP 1996 Neurogenic amplification of immune complex inflammation. Science 273 1722 1725

38. GarzaAWeinstockJVRobinsonP 2008 Absence of the SP/SP receptor circuitry in the substance P-precursor knockout mice or SP receptor, neurokinin (NK)1 knockout mice leads to an inhibited cytokine response in granulomas associated with murine Taenia crassiceps infection. J Parasitol 94 1253 1258

39. RacineRJ 1972 Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32 281 294