Evidence map›Paper›PMID 39400809›Full record

ArticleAdvances in experimental medicine and biology2024

Monoacylglycerol Lipase Inhibition Using ABX-1431 Attenuates Cerebral Ischaemia Early After Traumatic Brain Injury.

Denis E Bragin, Olga A Bragina, Dan P Covey, Alex O Trofimov, Edwin M Nemoto, Andrew R Mayer

Abstract read
In one paragraph

Article in Advances in experimental medicine and biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed.

  1. Review
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

6 authors.

Denis E BraginLovelace Biomedical Research Institute, Albuquerque, NM, USA. dbragin@lrri.org.
Olga A BraginaLovelace Biomedical Research Institute, Albuquerque, NM, USA.
Dan P CoveyLovelace Biomedical Research Institute, Albuquerque, NM, USA.
Alex O TrofimovPrivolzhsky Research Medical University, Nizhny Novgorod, Russia.
Edwin M NemotoDepartment of Neurology, University of New Mexico School of Medicine, Albuquerque, NM, USA.
Andrew R MayerLovelace Biomedical Research Institute, Albuquerque, NM, USA.

Funding

University of New Mexico (UNM) Center for Brain Recovery and RepairP20GM109089 · NIGMS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI SHUTTLEWORTH, CLAUDE W · 2015 to 2024
$22.7M
Pilot Project Program (PPP)P30GM122734 · NIGMS · THE MIND RESEARCH NETWORK · PI MAYER, ANDREW ROBERT · 2018 to 2022
$7.0M
Brain Injury Treatment by Modulation of Hemodynamics With Blood Soluble Drag Reducing MoleculesR01NS112808 · NINDS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI BRAGIN, DENIS E. · 2019 to 2023
$2.1M
The mechanisms of cerebral microcirculation response to transcranial stimulation.R21AG089266 · NIA · LOVELACE BIOMEDICAL RESEARCH INSTITUTE · PI BRAGINA, OLGA A · 2024 to 2024
$597k
Stroke Treatment by Modulation of Hemodynamics with Drag Reducing MoleculesR21NS091600 · NINDS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI BRAGIN, DENIS E. · 2015 to 2016
$423k
NIA NIH HHS R21 AG089266NIGMS NIH HHS P20 GM109089NIGMS NIH HHS P30 GM122734NINDS NIH HHS R01 NS112808NINDS NIH HHS R21 NS091600
6 · The paper itself

Abstract

An early event in the pathology of traumatic brain injury (TBI) is a reduction in cerebral blood flow (CBF), which exacerbates secondary injury development and inhibits brain recovery. The endogenous cannabinoid system signalling (eCBs) might be critical in TBI recovery due to modulating synaptic activity and exerting neuroprotective and anti-inflammatory effects. In the brain, eCBs predominantly occur at cannabinoid receptor type 1 via the eCB 2-arachidonoylglycerol (2-AG). The aim of this work was to test the efficacy of potentiating 2-AG signalling by monoacylglycerol lipase (MAGL) inhibition using ABX-1431 immediately following TBI. Laser speckle contrast imaging (LSCI) was used to create a high-resolution map of regional cerebral blood flow (CBF) over the pericontusion cortical surface. In-vivo two-photon laser scanning microscopy (2PLSM) was used to monitor cerebral microcirculation (i.v. fluorescein isothiocyanate dextran, FITC) and mitochondrial respiration and brain tissue oxygen supply (nicotinamide adenine dinucleotide autofluorescence, NADH) during 4 hours after CHI. After baseline imaging, male C57BL/6 J mice (10-12 weeks, >28 g) were subjected to a modified moderate Shohami weight-drop closed-head injury (CHI) followed by i.p. injection of ABX-1431 (5 mg/kg) or vehicle 30 min after the insult (10 mice per group). Differences between groups and between time points were determined using two-way repeated measures (ANOVA) for multiple comparisons and post hoc testing with the statistical significance level set at p < 0.05. Optical imaging revealed that CHI caused a decrease in regional CBF, arteriole diameters (vasospasm), and blood flow volume, leading to capillary microthrombosis and a reduction in capillary flow velocity. Compromised cerebral microcirculation led to the development of tissue hypoxia. ABX-1431 application, in a ~30-minute delay, mitigated the development of microvascular dysfunction, microthrombosis formation, and tissue hypoxia compared to the saline control group (p < 0.05, starting 1 hour after CHI). Therefore, MAGL inhibition by ABX-1431 attenuates cerebral ischaemia early after TBI. The observed 2-AG-mediated cerebrovascular relaxation might involve both a direct inhibition of smooth muscle contractility and a release of vasodilator mediator(s) from the endothelium.

Indexed as

Brain Injuries, TraumaticBrain IschemiaCerebrovascular CirculationMonoacylglycerol LipasesAnimalsArachidonic AcidsBenzodioxolesDisease Models, AnimalEndocannabinoidsEnzyme InhibitorsGlyceridesMaleMiceMice, Inbred C57BLPiperidines1,1,1,3,3,3-hexafluoropropan-2-yl 4-(bis(benzo(d)(1,3)dioxol-5-yl)(hydroxy)methyl)piperidine-1-carboxylateArachidonic AcidsBenzodioxolesEndocannabinoidsEnzyme InhibitorsGlyceridesglyceryl 2-arachidonateMonoacylglycerol LipasesPiperidinesDrag-reducing polymersIschaemiaSepsis

Identifiers

PMID39400809
PMCPMC12484365

What Socratic holds

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Read underepoch 390

Registered trials

None linked

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 Socratic graph.