Evidence map›Paper›PMID 36165953›Full record

ArticleSleep2022

Dual orexin antagonist normalized sleep homeostatic drive, enhanced GABAergic inhibition, and suppressed seizures after traumatic brain injury.

Sruthi R Konduru, Jesse R Isaacson, Danny J Lasky, Zihao Zhou, Rohan K Rao, Swati S Vattem, Sophie J Rewey, Mathew V Jones, Rama K Maganti

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Sleep, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 13 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Sruthi R KonduruDepartment of Neurology, Wayne State University, Detroit, MI, USA.
Jesse R IsaacsonDepartment of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Danny J LaskyDepartment of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.ORCID 0000-0002-1814-5713
Zihao ZhouRock Bridge High School, Columbia, MO, USA.
Rohan K RaoRock Bridge High School, Columbia, MO, USA.
Swati S VattemDepartment of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Sophie J ReweyDepartment of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Mathew V JonesDepartment of Neuroscience, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.ORCID 0000-0002-4655-8777
Rama K MagantiDepartment of Neurology, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
University of Wisconsin–Madison · USWayne State University · US

Funding

Sleep deprivation-induced seizure exacerbation: Targeting tonic inhibition as a therapeutic strategyR21NS104612 · NINDS · UNIVERSITY OF WISCONSIN-MADISON · PI MAGANTI, RAMA · 2018 to 2019
$408k
Department of Defense PRMRP:161864NIH HHS R21NS104612-01A1
6 · The paper itself

Abstract

STUDY

objectivesTraumatic brain injury (TBI) can result in posttraumatic epilepsy (PTE) and sleep disturbances. We hypothesized that treatment with sleep aids after TBI can ameliorate PTE.

methodsCD-1 mice underwent controlled cortical impact (CCI), sham injury, or no craniotomy. Sham and CCI groups underwent a monthlong daily treatment with sleep aids including a dual orexin antagonist (DORA-22) or THIP (gaboxadol) or a respective vehicle starting on the day of CCI. We performed continuous EEG (electroencephalography) recordings at week 1 and months 1, 2, and 3 for ~1 week each time. Seizure analysis occurred at all-time points and sleep analysis occurred in week 1 and month-1/2 in all groups. Subsets of CCI and sham groups were subjected to voltageclamp experiments in hippocampal slices to evaluate GABAergic synaptic inhibition.

resultsDORA-22 treatment suppressed seizures in month 1-3 recordings. TBI reduced the amplitude and frequency of miniature inhibitory synaptic currents (mIPSCs) in dentate granule cells and these changes were rescued by DORA-22 treatment. Sleep analysis showed that DORA-22 increased nonrapid eye movement (NREM) sleep during lights-off whereas THIP increased REM sleep during lights-on in week 1. Both treatments displayed subtle changes in time spent in NREM or REM at month-1/2 as well. TBI not only increased normalized EEG delta power (NΔ) at week-1 and month-1 but also resulted in the loss of the homeostatic diurnal oscillation of NΔ, which was restored by DORA-22 but not THIP treatment.

conclusionsDual orexin antagonists may have a therapeutic potential in suppressing PTE potentially by enhancing GABAergic inhibition and impacting sleep homeostatic drive.

Indexed as

Brain Injuries, TraumaticAnimalsElectroencephalographyMiceOrexin Receptor AntagonistsSeizuresSleepOrexin Receptor AntagonistsNREM delta powerposttraumatic epilepsysleep disordersTBI

Identifiers

PMID36165953
PMCPMC9742898
OpenAlexW4297262624

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.