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The effect of Glibenclamide on somatosensory evoked potentials after cardiac arrest in rats

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Abstract

Background

Science continues to search for a neuroprotective drug therapy to improve outcomes after cardiac arrest (CA). The use of glibenclamide (GBC) has shown promise in preclinical studies, but its effects on neuroprognostication tools are not well understood. We aimed to investigate the effect of GBC on somatosensory evoked potential (SSEP) waveform recovery post CA and how this relates to the early prediction of functional outcome, with close attention to arousal and somatosensory recovery, in a rodent model of CA.

Methods

Sixteen male Wistar rats were subjected to 8-min asphyxia CA and assigned to GBC treatment (n = 8) or control (n = 8) groups. GBC was administered as a loading dose of 10 μg/kg intraperitoneally 10 min after the return of spontaneous circulation, followed by a maintenance dosage of 1.6 μg/kg every 8 h for 24 h. SSEPs were recorded from baseline until 150 min following CA. Coma recovery, arousal, and brainstem function, measured by subsets of the neurological deficit score (NDS), were compared between both groups. SSEP N10 amplitudes were compared between the two groups at 30, 60, 90, and 120 min post CA.

Results

Rats treated with GBC had higher sub-NDS scores post CA, with improved arousal and brainstem function recovery (P = 0.007). Both groups showed a gradual improvement of SSEP N10 amplitude over time, from 30 to 120 min post CA. Rats treated with GBC showed significantly better SSEP recovery at every time point (P < 0.001 for 30, 60, and 90 min; P = 0.003 for 120 min). In the GBC group, the N10 amplitude recovered to baseline by 120 min post CA. Quantified Cresyl violet staining revealed a significantly greater percentage of damage in the control group compared with the GBC treatment group (P = 0.004).

Conclusions

Glibenclamide improves coma recovery, arousal, and brainstem function after CA with decreased number of ischemic neurons in a rat model. GBC improves SSEP recovery post CA, with N10 amplitude reaching the baseline value by 120 min, suggesting early electrophysiologic recovery with this treatment. This medication warrants further exploration as a potential drug therapy to improve functional outcomes in patients after CA.

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Funding

The work was supported by R01HL118084 and R01NS110387 from the United States National Institutes of Health (both to XJ). XJ was partially supported by the National Institutes of Health RO1 NS117102 (to XJ).

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Authors and Affiliations

  1. Program in Trauma, Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA

    Brittany Bolduc Lachance & Neeraj Badjatia

  2. Department of Neurosurgery, University of Maryland School of Medicine, 685 West Baltimore Street, MSTF Building 823, Baltimore, MD, 21201, USA

    Zhuoran Wang & Xiaofeng Jia

  3. Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD, USA

    Xiaofeng Jia

  4. Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA

    Xiaofeng Jia

  5. Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Xiaofeng Jia

  6. Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Xiaofeng Jia

Authors
  1. Brittany Bolduc Lachance
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  2. Zhuoran Wang
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  3. Neeraj Badjatia
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  4. Xiaofeng Jia
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Contributions

Brittany Bolduc Lachance analyzed the data and wrote the article and worked on the revision, Zhuoran Wang performed the in vivo study and related in vitro study. Neeraj Badjatia provided critical appraisal. Xiaofeng Jia conceived the original idea, designed the experiments, revised, and finalized the article. The authors read and approved the final manuscript.

Corresponding author

Correspondence to Xiaofeng Jia.

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The authors declare no conflict of interest.

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Experimental protocols were approved by the University of Maryland Baltimore Institutional Animal Care and Use Committee.

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Lachance, B.B., Wang, Z., Badjatia, N. et al. The effect of Glibenclamide on somatosensory evoked potentials after cardiac arrest in rats. Neurocrit Care 36, 612–620 (2022). https://doi.org/10.1007/s12028-021-01350-w

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  • DOI: https://doi.org/10.1007/s12028-021-01350-w

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