Evidence map›Paper›PMID 39463282›Full record

ArticleJournal of neurotrauma2025

A Combination of Low Doses of Lithium and Valproate Improves Cognitive Outcomes after Mild Traumatic Brain Injury.

John B Redell, Mark E Maynard, Michael J Hylin, Kimberly N Hood, Andrea Sedlock, Dragan Maric, Jing Zhao, Anthony N Moore, Badrinath Roysam, Shibani Pati and 1 more

Abstract read
In one paragraph

Article in Journal of neurotrauma, 2025. 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
–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

2 citing papers in PubMed.

  1. Article
  2. Article
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

11 authors.

John B RedellDepartment of Neurobiology and Anatomy, The University of Texas McGovern Medical School, Houston, Texas, USA.
Mark E MaynardDepartment of Electrical and Computer Engineering, University of Houston, Houston, Texas, USA.
Michael J HylinDepartment of Neurobiology and Anatomy, The University of Texas McGovern Medical School, Houston, Texas, USA.ORCID 0000-0002-8600-3047
Kimberly N HoodDepartment of Neurobiology and Anatomy, The University of Texas McGovern Medical School, Houston, Texas, USA.
Andrea SedlockFlow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bethesda, Maryland, USA.
Dragan MaricFlow and Imaging Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH), Bethesda, Maryland, USA.
Jing ZhaoDepartment of Neurobiology and Anatomy, The University of Texas McGovern Medical School, Houston, Texas, USA.
Anthony N MooreDepartment of Neurobiology and Anatomy, The University of Texas McGovern Medical School, Houston, Texas, USA.
Badrinath RoysamDepartment of Electrical and Computer Engineering, University of Houston, Houston, Texas, USA.
Shibani PatiDepartments of Pathology and Laboratory Medicine, UCSF, San Francisco, California, USA.
Pramod K DashDepartment of Neurobiology and Anatomy, The University of Texas McGovern Medical School, Houston, Texas, USA.

Funding

Comprehensive Quantitative Profiling of Cellular Alterations Caused by InjuryR01NS109118 · NINDS · UNIVERSITY OF HOUSTON · PI DASH, PRAMOD K, REDELL, JOHN B · 2019 to 2023
$3.2M
NINDS NIH HHS R01 NS109118
6 · The paper itself

Abstract

The prevalence of mild traumatic brain injury (mTBI) is high compared with moderate and severe TBI, comprising almost 80% of all brain injuries. mTBI activates a complex cascade of biochemical, molecular, structural, and pathological changes that can result in neurological and cognitive impairments. These impairments can manifest even in the absence of overt brain damage. Given the complexity of changes triggered by mTBI, a combination of drugs that target multiple TBI-activated cascades may be required to improve mTBI outcomes. It has been previously demonstrated that cotreatment with the U.S. Food and Drug Administration (FDA)-approved drugs lithium plus valproate (Li + VPA) for 3 weeks after a moderate-to-severe controlled cortical impact injury reduced cortical tissue loss and improved motor function. Since both lithium and valproate can exhibit toxicity at high doses, it would be beneficial to determine if this combination treatment is effective when administered at low doses and for a shorter duration, and if it can improve cognitive function, after a mild diffuse TBI. In the present study, we tested if the combination of low doses of lithium (1 mEq/kg or 0.5 mEq/kg) plus valproate (20 mg/kg) administered for 3 days after a mild fluid percussion injury can improve hippocampal-dependent learning and memory. Our data show that the combination of low-dose Li + VPA improved spatial learning and memory, effects not seen when either drug was administered alone. In addition, postinjury Li + VPA treatment improved recognition memory and sociability and reduced fear generalization. Postinjury Li + VPA also reduced the number of anti-ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia counted using a convolutional neural network, indicating a reduction in neuroinflammation. These findings indicate that low-dose Li + VPA administered acutely after mTBI may have translational utility to reduce pathology and improve cognitive function.

Indexed as

Brain ConcussionCognitionCognitive DysfunctionValproic AcidAnimalsDose-Response Relationship, DrugDrug Therapy, CombinationMaleRatsTreatment OutcomeValproic Acidcombination therapyconcussionconvolutional neural networkfluid percussion injurylearning and memoryneuroinflammation

Identifiers

PMID39463282
PMCPMC11971536

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.