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Evaluation of the effects of riluzole on adult spinal cord‐derived neural stem/progenitor cells <i>in vitro</i> and <i>in vivo</i>

2015· article· en· W1887007270 on OpenAlexafffund
Laureen D. Hachem, Andrea J. Mothe, Charles H. Tator

Bibliographic record

VenueInternational Journal of Developmental Neuroscience · 2015
Typearticle
Languageen
FieldMedicine
TopicSpinal Cord Injury Research
Canadian institutionsUniversity of TorontoToronto Western HospitalUniversity Health Network
FundersKrembil FoundationToronto General and Western Hospital FoundationAmerican Association of Neurological Surgeons
KeywordsRiluzolePharmacologyExcitotoxicityNeuroprotectionGlutamate receptorViability assayProgenitor cellEx vivoSpinal cord injurySpinal cordChemistryMedicineStem cellIn vitroBiologyNeuroscienceCell biologyBiochemistryReceptor

Abstract

fetched live from OpenAlex

Riluzole, a sodium/glutamate antagonist, has shown significant neuroprotective effects in experimental models of spinal cord injury (SCI) and is currently under clinical trial for patients with SCI. However, the effect of riluzole on adult spinal cord-derived NSPCs remains unknown. In this study, we examined the effects of riluzole on NSPC survival both in vitro and in vivo. NSPCs harvested from the adult rat spinal cord were exposed to riluzole (1-30 μM) either alone or in combination with hydrogen peroxide or glutamate in vitro. Measures of intracellular reactive oxygen species (ROS), cell viability and proliferation were assessed. To examine the effects of riluzole on transplanted NSPCs in vivo, a rodent clip compression model of SCI was used. One week after injury, NSPCs were transplanted into the spinal cord and rats received either riluzole or vehicle treatment for two weeks (similar to the clinically accepted dosing regimen) at which time cords were processed for analysis. Exposure to riluzole (≥ 10 μM) for more than 48 h in vitro reduced NSPC viability. Riluzole treatment (1-10 μM) did not significantly affect intracellular ROS levels or cell viability in the setting of in vitro oxidative stress. While glutamate (500 μM) exposure for 96 h significantly increased adult NSPC proliferation and survival, this response was not blocked by concurrent treatment with riluzole (1-10 μM) thus supporting the notion that the known anti-glutamatergic properties of riluzole are not mediated through direct inhibition of glutamate receptors. Furthermore, riluzole treatment did not impair the survival of transplanted NSPCs in a rodent model of SCI. These results suggest that although NSPCs may have a narrow tolerance to riluzole treatment in vitro, riluzole does not impair NSPC survival at doses that would be used clinically.

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)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.101
Threshold uncertainty score0.302

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.058
GPT teacher head0.366
Teacher spread0.308 · 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 designBench or experimental
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

Citations9
Published2015
Admission routes2
Has abstractyes

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