Effect of intracerebroventricular continuous infusion of valproic acid versus single i.p. and i.c.v. injections in the amygdala kindling epilepsy model
Abstract
Two protocols were tested to assess anticonvulsant efficacy and drug concentrations after intracerebroventricular (i.c.v.) continuous valproic acid (VPA) infusion, as compared with acute injections in the kindling epilepsy model. Protocol 1: amygdala-kindled rats were injected via intraperitoneal (i.p.) and i.c.v. routes with varying doses of VPA and tested for seizure intensity, afterdischarge and seizure duration, ataxia and sedation. Concentrations of VPA were determined by immunofluorescence in the brain, plasma, cerebrospinal fluid (CSF) and liver in matching rats. Protocol 2: amygdala-kindled rats were implanted with osmotic minipumps containing a VPA solution in saline and connected to intraventricular catheters for 7 days. Seizure threshold, latency and duration, afterdischarge duration, ataxia and sedation were recorded daily before, during, and until 5 days after VPA infusion. In matching animals, CSF, brain, plasma and liver VPA concentration was determined. Acute i.c.v. VPA injection suppressed seizures with a remarkable ataxia and sedation. However, continuous i.c.v. infusion controlled generalised and even focal seizures without producing important side effects, high plasma levels or hepatic drug concentrations. In conclusion, continuous i.c.v. VPA infusion may protect against kindled seizures by minimising ataxia and sedation, and achieving suitable intracerebral, yet low plasma or hepatic drug concentrations, thus avoiding potential systemic toxicity.
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The ED50 of drugs injected through i.c.v. route is usually around 10-fold less than ED50 of drugs injected through i.p. route.
“Since the ED50 (median effective dose value) of drugs injected through an intracerebroventricular (i.c.v.) route is usually around 10-fold less than the ED50 of drugs injected through an i.p. route to achieve a similar effect on the brain”
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- Authors
- Serralta, A., Barcia, J. A., Ortiz, P., Durán, C., Hernández, M. E., & Alós, M.
- Affiliations
- Hospital Universitari i Politècnic La Fe (ES)
- Hospital General Universitario De Valencia (ES)
- Corresponding author
- Barcia, Juan A.
- Venue
- Epilepsy Research
- Publisher
- Elsevier BV
- Published
- 2006-07
- Volume
- 70
- Issue
- 1
- Pages
- 15-26
- ISSN
- 0920-1211 (ISSN-L)
- OpenAlex
- W2059505070
- Cited by
- 33
- References
- 0
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 1 · 2020: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 2 · 2013: 2 · 2012: 3
- FWCI
- 1.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Epilepsy Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- valproic acid, amygdala kindling, intracerebroventricular infusion, osmotic minipump, anticonvulsant efficacy, afterdischarge, seizure threshold, drug concentration distribution, cerebrospinal fluid, systemic toxicity
- MeSH terms
- Amygdala, Animals, Anticonvulsants, Cerebral Ventricles, Disease Models, Animal, Dose-Response Relationship, Drug, Epilepsy, Infusions, Parenteral, Injections, Intraventricular, Kindling, Neurologic, Male, Valproic Acid, Rats, Wistar, Rats
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