Unifying mechanism behind the onset of acquired epilepsy

Larvae of the cestodes Taenia solium and Taenia crassiceps infect the central nervous system of humans. Taenia solium larvae in the brain cause neurocysticercosis, the leading cause of adult-acquired epilepsy worldwide. Relatively little is understood about how cestode-derived products modulate host neural and immune signalling. Acetylcholinesterases, a class of enzyme that breaks down acetylcholine, are produced by a host of parasitic worms to aid their survival in the host. Acetylcholine is an important signalling molecule in both the human nervous and immune systems, with powerful modulatory effects on the excitability of cortical networks. Therefore, it is important to establish whether cestode derived acetylcholinesterases may alter host neuronal cholinergic signalling. Here we make use of multiple techniques to profile acetylcholinesterase activity in different extracts of both Taenia crassiceps and Taenia solium larvae. We find that the larvae of both species contain substantial acetylcholinesterase activity. However, acetylcholinesterase activity is lower in Taenia solium as compared to Taenia crassiceps larvae. Further, whilst we observed acetylcholinesterase activity in all fractions of Taenia crassiceps larvae, including on the membrane surface and in the excreted/secreted extracts, we could not identify acetylcholinesterases on the membrane surface or in the excreted/secreted extracts of Taenia solium larvae. Bioinformatic analysis revealed conservation of the functional protein domains in the Taenia solium acetylcholinesterases, when compared to the homologous human sequence. Finally, using whole-cell patch clamp recordings in rat hippocampal brain slice cultures, we demonstrate that Taenia larval derived acetylcholinesterases can break down acetylcholine at a concentration which induces changes in neuronal signalling. Together, these findings highlight the possibility that Taenia larval acetylcholinesterases can interfere with cholinergic signalling in the host, potentially contributing to pathogenesis in neurocysticercosis.

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Erratum to “Cellular mechanisms underlying acquired epilepsy: The calcium hypothesis of the induction and maintenance of epilepsy” [Pharmacol. Ther. 105(3) (2005) 229–266]

Pharmacology & Therapeutics ◽

10.1016/j.pharmthera.2005.09.001 ◽

2006 ◽

Vol 111 (1) ◽

pp. 287 ◽

Cited By ~ 1

Author(s):

Robert J. DeLorenzo ◽

David A. Sun ◽

Laxmiant S. Deshpande

Keyword(s):

Cellular Mechanisms ◽

Acquired Epilepsy

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Acquired Epilepsy: Cellular and Molecular Mechanisms

Molecular Neurology ◽

10.1016/b978-012369509-3.50025-1 ◽

2007 ◽

pp. 347-370 ◽

Cited By ~ 2

Author(s):

Christopher B. Ransom ◽

Hal Blumenfeld

Keyword(s):

Molecular Mechanisms ◽

Acquired Epilepsy

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Frequency and Determinant Factors for Calcification in Neurocysticercosis

Clinical Infectious Diseases ◽

10.1093/cid/ciaa784 ◽

2020 ◽

Cited By ~ 4

Author(s):

Javier A Bustos ◽

Gianfranco Arroyo ◽

Robert H Gilman ◽

Percy Soto-Becerra ◽

Isidro Gonzales ◽

...

Keyword(s):

Risk Factors ◽

Confidence Interval ◽

Antibody Response ◽

Human Brain ◽

Risk Ratio ◽

Factors Associated ◽

Patient Level ◽

Increased Risk ◽

Acquired Epilepsy ◽

Antiparasitic Treatment

Abstract Background Neurocysticercosis is a major cause of acquired epilepsy. Larval cysts in the human brain eventually resolve and either disappear or leave a calcification that is associated with seizures. In this study, we assessed the proportion of calcification in parenchymal neurocysticercosis and risk factors associated with calcification. Methods Data for 220 patients with parenchymal NCC from 3 trials of antiparasitic treatment were assessed to determine what proportion of the cysts that resolved 6 months after treatment ended up in a residual calcification at 1 year. Also, we evaluated the risk factors associated with calcification. Results The overall proportion of calcification was 38% (188/497 cysts, from 147 patients). Predictors for calcification at the cyst level were cysts larger than 14 mm (risk ratio [RR], 1.34; 95% confidence interval [CI], 1.02–1.75) and cysts with edema at baseline (RR, 1.39; 95% CI, 1.05–1.85). At the patient level, having had more than 24 months with seizures (RR, 1.25; 95% CI, 1.08–1.46), mild antibody response (RR, 1.14; 95% CI, 1.002–1.27), increased dose albendazole regime (RR, 1.26; 95% CI, 1.14–1.39), lower doses of dexamethasone (RR, 1.36; 95% CI, 1.02–1.81), not receiving early antiparasitic retreatment (RR, 1.45; 95% CI, 1.08–1.93), or complete cure (RR, 1.48; 95% CI, 1.29–1.71) were associated with a increased risk of calcification. Conclusions Approximately 38% of parenchymal cysts calcify after antiparasitic treatment. Some factors associated with calcification are modifiable and may be considered to decrease or avoid calcification, potentially decreasing the risk for seizure relapses.

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Epigenetics in acquired epilepsy

Pharmacological Reports ◽

10.1016/j.pharep.2014.11.018 ◽

2015 ◽

Vol 67 (1) ◽

pp. 168

Author(s):

Katarzyna Łukasiuk

Keyword(s):

Acquired Epilepsy

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Amazon rainforest rodents (Proechimys) are resistant to post-stroke epilepsy

Scientific Reports ◽

10.1038/s41598-021-96235-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nancy N. Ortiz-Villatoro ◽

Selvin Z. Reyes-Garcia ◽

Leandro Freitas ◽

Laís D. Rodrigues ◽

Luiz E. C. Santos ◽

...

Keyword(s):

Wistar Rats ◽

Laboratory Research ◽

Post Injury ◽

Post Stroke ◽

Brain Responses ◽

Conventional Animal ◽

Acquired Epilepsy ◽

Brain Insults

AbstractThere are no clinical interventions to prevent post-injury epilepsy, a common and devastating outcome after brain insults. Epileptogenic events that run from brain injury to epilepsy are poorly understood. Previous studies in our laboratory suggested Proechimys, an exotic Amazonian rodent, as resistant to acquired epilepsy development in post-status epilepticus models. The present comparative study was conducted to assess (1) stroke-related brain responses 24-h and 30 days after cortical photothrombosis and (2) post-stroke epilepsy between Proechimys rodents and Wistar rats, a traditional animal used for laboratory research. Proechimys group showed smaller volume of ischemic infarction and lesser glial activation than Wistar group. In contrast to Wistar rats, post-stroke decreased levels of pro-inflammatory cytokines and increased levels of anti-inflammatory mediators and growth factors were found in Proechimys. Electrophysiological signaling changes assessed by cortical spreading depression, in vitro and in vivo, showed that Wistar’s brain is most severely affected by stroke. Chronic electrocorticographic recordings showed that injury did not lead to epilepsy in Proechimys whereas 88% of the Wistar rats developed post-stroke epilepsy. Science gains insights from comparative studies on diverse species. Proechimys rodents proved to be a useful animal model to study antiepileptogenic mechanisms after brain insults and complement conventional animal models.

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