Evidence map›Paper›PMID 38443709›Full record

ArticleNeurocritical care2024

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study.

Matthew C Culkin, Priyanka Bele, Anastasia P Georges, Patricia Santos, Grace Niziolek, Lewis J Kaplan, Douglas H Smith, Jose L Pascual

Abstract read
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In one paragraph

Article in Neurocritical care, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

2 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
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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

8 authors at 1 institution in 1 country.

Matthew C CulkinDivision of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, SICU Administration Office - 5 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Priyanka BeleDivision of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, SICU Administration Office - 5 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Anastasia P GeorgesCenter for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Patricia SantosDivision of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, SICU Administration Office - 5 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Grace NiziolekDivision of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, SICU Administration Office - 5 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Lewis J KaplanDivision of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, SICU Administration Office - 5 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104, USA.
Douglas H SmithCenter for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jose L PascualDivision of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, SICU Administration Office - 5 Founders Pavilion, 3400 Spruce Street, Philadelphia, PA, 19104, USA. jose.pascual@pennmedicine.upenn.edu.ORCID 0000-0002-1613-7912
University of Pennsylvania · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEarly posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery.

methodsCD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60 mg/kg). At 48 h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia Neurological Test scores and animal weight changes at 24 h and 48 h after injury.

resultsI + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24 h and 48 h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I + TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group.

conclusionsOnly higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

Indexed as

Antifibrinolytic AgentsBlood-Brain BarrierBrain Injuries, TraumaticDose-Response Relationship, DrugTranexamic AcidAnimalsCapillary PermeabilityDisease Models, AnimalLeukocyte RollingLeukocytesMaleMiceAntifibrinolytic AgentsTranexamic AcidBlood–brain barrierDosingLeukocytesPermeabilityTBITranexamic acid

Identifiers

PMID38443709
OpenAlexW4392448424

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.