ArticleNeuromolecular medicine2010
Homocysteine potentiates seizures and cell loss induced by pilocarpine treatment.
Article in Neuromolecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to epilepsy.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2018Pooled it
- Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy.BMC neurology · 2024Article
- Epigallocatechin-3-gallate Enhances Cognitive and Memory Performance and Protects Against Brain Injury in Methionine-induced Hyperhomocysteinemia Through Interdependent Molecular Pathways.Neurotoxicity research · 2022Article
- Higher susceptibility to 6 Hz corneal kindling and lower responsiveness to antiseizure drugs in mouse models of Alzheimer's disease.Epilepsia · 2022Article
- Neuroprotective Potential of Ellagic Acid: A Critical Review.Advances in nutrition (Bethesda, Md.) · 2021Review
- Physiological and Biochemical Markers of the Sex-Specific Sensitivity to Epileptogenic Factors, Delayed Consequences of Seizures and Their Response to Vitamins B1 and B6 in a Rat Model.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Genetic Polymorphisms in Enzymes Involved in One-Carbon Metabolism and Anti-epileptic Drug Monotherapy on Homocysteine Metabolism in Patients With Epilepsy.Frontiers in neurology · 2021Article
- Nanoformulated ellagic acid ameliorates pentylenetetrazol-induced experimental epileptic seizures by modulating oxidative stress, inflammatory cytokines and apoptosis in the brains of male mice.Metabolic brain disease · 2020Article
- A new mechanism for cannabidiol in regulating the one-carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models.British journal of pharmacology · 2020Article
- Short-Term and Long-Term Effects of Levetiracetam Monotherapy on Homocysteine Metabolism in Children with Epilepsy: A Prospective Study.Journal of clinical neurology (Seoul, Korea) · 2019Article
- Role of Homocysteine in the Ischemic Stroke and Development of Ischemic Tolerance.Frontiers in neuroscience · 2016Review
- Mechanisms involved in the ischemic tolerance in brain: effect of the homocysteine.Cellular and molecular neurobiology · 2015Review
- Spinal cord demyelination combined with hyperhomocysteinemia: a case report.Neuropsychiatric disease and treatment · 2014Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patients affected by recurrent seizures frequently present increased homocysteine plasma levels in consequence of treatment with antiepileptic drugs. Homocysteine is proconvulsant and can affect the response to antiepileptic drugs. In addition, high homocysteine plasma levels represent a risk factor for cardiovascular and neurodegenerative diseases. To better define the role of increased homocysteine in epilepsy, we analyzed the effects of homocysteine pretreatment in the pilocarpine model of status epilepticus (SE), which is used to mimic temporal lobe epilepsy (TLE) in rodents. Precisely, we investigated whether a moderate hyperhomocysteinemia, unable to cause seizures, could sensitize rats to pilocarpine and cooperate in inducing brain lesions. We found that a subthreshold dose of pilocarpine (200 mg/kg) is sufficient to induce SE in the majority (approximately 90%) of rats pretreated with homocysteine for 2 weeks, whereas only 40% of saline-treated controls developed SE following the same pilocarpine dose. Furthermore, homocysteine pretreatment led to a significant increase in neuronal cell loss evaluated by counting toluidine blue-stained or Fluoro-Jade-positive cells in hippocampal and parahippocampal regions. Pilocarpine augmented amyloid beta expression in both animal groups. However, pretreatment with homocysteine favored the intraneuronal fibrillar conformation of amyloid beta, thus promoting neurodegeneration. These findings indicate that increased homocysteine levels enhance seizure activity and neurodegeneration in pilocarpine-treated rats and suggest that similar detrimental effects may occur in patients affected by TLE.
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Registered trials
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