Continuous bilateral infusion of vigabatrin into the subthalamic nucleus: Effects on seizure threshold and GABA metabolism in two rat models
Open accessAbstract
The subthalamic nucleus (STN) plays a crucial role as a regulator of basal ganglia outflow but also influences the activity of cortical and limbic structures, so that it is widely used as a therapeutic target in different brain diseases, including epilepsy. In addition to electrical stimulation of the STN, targeted delivery of anti-seizure drugs to the STN may constitute an alternative treatment approach in patients with pharmacoresistant epilepsy. In the present experimental study, we investigated the anti-seizure and adverse effects of chronic infusion of vigabatrin into the STN of rats. Vigabatrin is a clinically approved anti-seizure drug, which acts by increasing brain GABA levels by irreversibly inhibiting GABA-aminotransferase (GABA-T). Based on functional and neurochemical effects of acute STN microinjection, doses for continuous infusion were calculated and administered, using an innovative drug infusion technology. Bilateral infusion of only 10μg/day vigabatrin over 3weeks into the STN resulted in an almost complete inhibition of GABA-T and 4-fold increase in GABA in the target region, which was associated with a significant increase in seizure threshold, determined once weekly by i.v. infusion of pentylenetetrazole (PTZ). Lower doses or unilateral infusion were less effective, both on PTZ seizures and on kindled seizures. Bilateral infusion into substantia nigra pars reticulata was less effective and more toxic than STN infusion. In part of the rats, tolerance to t…
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Intracerebral injections are clinically feasible and are performed in a variety of clinical scenarios and preclinical settings.
“Intracerebral injections are clinically feasible, and are performed in a variety of clinical scenarios (17–23), as well as in various preclinical settings (4, 24–27).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [25]
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Policy: NIH to balance sex in cell and animal studies
Clayton, J. A., & Collins, F. S. (2014) · Nature · doi:10.1038/509282a · Cited by 1,816 · see citing works
Serralta, A., Barcia, J. A., Ortiz, P., Durán, C., Hernández, M. E., & Alós, M. (2006) · Epilepsy Research · doi:10.1016/j.eplepsyres.2006.02.003 · Cited by 33 · cited 2× · see citing works
“infusion of valproate exerted significant anti-seizure effects in the kindling model (Serralta et al., 2006).”
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Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection
Tuma, J., Chen, Y.-J., Collins, M. G., Paul, A., Li, J., Han, H., Sharma, R., Murthy, N., & Lee, H. Y. (2023) · Biochemistry · doi:10.1021/acs.biochem.3c00371 · Cited by 65 · see citing works
- Authors
- Gey, L., Gernert, M., & Löscher, W.
- Affiliations
- University of Veterinary Medicine Hannover, Foundation (DE)
- Corresponding author
- Gernert, Manuela
- Löscher, Wolfgang
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 91
- Pages
- 194-208
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2295790987
- Cited by
- 21
- References
- 2
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 5 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 1
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Deutsche Forschungsgemeinschaft (GE 1103/7-2)
- Konrad-Adenauer-Stiftung
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Keywords
- vigabatrin, subthalamic nucleus, GABA metabolism, seizure threshold, drug-resistant epilepsy, kindled seizures, pentylenetetrazole-induced seizures, substantia nigra pars reticulata, drug tolerance, targeted drug delivery, basal ganglia
- MeSH terms
- Animals, Basal Ganglia, Disease Models, Animal, Electric Stimulation, Female, gamma-Aminobutyric Acid, Microinjections, Pentylenetetrazole, Seizures, Substantia Nigra, Rats, Wistar, Subthalamic Nucleus, Vigabatrin
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