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Investigating anti-inflammatory and immunomodulatory properties of brivaracetam and lacosamide in experimental autoimmune encephalomyelitis (EAE)

2023· article· en· W4324135647 on OpenAlexafffund
Oumarou Ouédraogo, Renaud Balthazard, Victoria Mamane, Hélène Jamann, Florence Millette, Audrey Daigneault, Nathalie Arbour, Catherine Larochelle

Bibliographic record

VenueEpilepsy Research · 2023
Typearticle
Languageen
FieldMedicine
TopicMultiple Sclerosis Research Studies
Canadian institutionsUniversité de Montréal
FundersCanadian Institutes of Health Research
KeywordsLacosamideExperimental autoimmune encephalomyelitisEpilepsyMedicineImmunologyMultiple sclerosis

Abstract

fetched live from OpenAlex

Inflammation plays a role in drug-resistant epilepsy (DRE). We have previously reported an increased proportion of CD4 T cells displaying a pro-inflammatory profile in the peripheral blood of adults with DRE. Specific anti-epileptic drugs (AEDs) exhibit immunomodulatory properties that could increase the risk of infections but also contribute to their beneficial impact on DRE and other neurological diseases. The impact of novel generation AEDs on the profile of immune cells and on neuroinflammatory processes remains unclear. We compared the influence of brivaracetam and lacosamide on the activation of human and murine peripheral immune cells in vitro and in vivo in active experimental autoimmune encephalomyelitis (EAE), a common mouse model of central nervous system inflammation. We found that brivaracetam and lacosamide at 2.5 μg/ml did not impair the survival and activation of human immune cells, but a higher dose of 25 μg/ml decreased mitogen-induced proliferation of CD8 T cells in vitro. Exposure to high doses of brivaracetam, and to a lesser extent lacosamide, reduced the proportion of CD25+ and CD107a+ CD8+ human T cells in vitro, and the frequency of CNS-infiltrating CD8+ T cells at EAE onset and CD11b+ myeloid cells at peak in vivo. Prophylactic administration of brivaracetam or lacosamide did not delay EAE onset but significantly improved the clinical course in the chronic phase of EAE compared to control. Novel generation AEDs do not impair the response to immunization with MOG peptide but improve the course of EAE, possibly through a reduction of neuroaxonal damage.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.592
Threshold uncertainty score0.667

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.002
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.116
GPT teacher head0.371
Teacher spread0.256 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2023
Admission routes2
Has abstractyes

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