Evidence map›Paper›PMID 24937045›Full record

ArticleNeuropharmacology2014

The fatty acid amide hydrolase inhibitor PF-3845 promotes neuronal survival, attenuates inflammation and improves functional recovery in mice with traumatic brain injury.

Flaubert Tchantchou, Laura B Tucker, Amanda H Fu, Rebecca J Bluett, Joseph T McCabe, Sachin Patel, Yumin Zhang

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

Article in Neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
10.1field-weighted citation impact, top 1% 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

57 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. The effect of traumatic brain injury on learning and memory: A synaptic focus.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025
    Review
  5. Cannabinoids: Role in Neurological Diseases and Psychiatric Disorders.International journal of molecular sciences · 2024
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Administration of ΔCannabis and cannabinoid research · 2022
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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

7 authors at 2 institutions in 1 country.

Flaubert TchantchouDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Laura B TuckerDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Amanda H FuDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Rebecca J BluettDepartments of Psychiatry and Molecular Physiology & Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Joseph T McCabeDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Sachin PatelDepartments of Psychiatry and Molecular Physiology & Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Yumin ZhangDepartment of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA; Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. Electronic address: yumin.zhang@usuhs.edu.
Uniformed Services University of the Health Sciences · USVanderbilt University Medical Center · US

Funding

Substrate-selective inhibition of COX-2 to target affective disordersR01MH100096 · NIMH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PATEL, SACHIN · 2013 to 2018
$2.4M
Stress adaptations in endocannabinoid signaling in the amygdalaK08MH090412 · NIMH · VANDERBILT UNIVERSITY · PI PATEL, SACHIN · 2010 to 2014
$842k
NIMH NIH HHS K08 MH090412NIMH NIH HHS MH090412NIMH NIH HHS MH100096NIMH NIH HHS R01 MH100096
6 · The paper itself

Abstract

Traumatic brain injury (TBI) is the leading cause of death in young adults in the United States, but there is still no effective agent for treatment. N-arachidonoylethanolamine (anandamide, AEA) is a major endocannabinoid in the brain. Its increase after brain injury is believed to be protective. However, the compensatory role of AEA is transient due to its rapid hydrolysis by the fatty acid amide hydrolase (FAAH). Thus, inhibition of FAAH can boost the endogenous levels of AEA and prolong its protective effect. Using a TBI mouse model, we found that post-injury chronic treatment with PF3845, a selective and potent FAAH inhibitor, reversed TBI-induced impairments in fine motor movement, hippocampus dependent working memory and anxiety-like behavior. Treatment with PF3845 inactivated FAAH activity and enhanced the AEA levels in the brain. It reduced neurodegeneration in the dentate gyrus, and up-regulated the expression of Bcl-2 and Hsp70/72 in both cortex and hippocampus. PF3845 also suppressed the increased production of amyloid precursor protein, prevented dendritic loss and restored the levels of synaptophysin in the ipsilateral dentate gyrus. Furthermore, PF3845 suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 and enhanced the expression of arginase-1 post-TBI, suggesting a shift of microglia/macrophages from M1 to M2 phenotype. The effects of PF3845 on TBI-induced behavioral deficits and neurodegeneration were mediated by activation of cannabinoid type 1 and 2 receptors and might be attributable to the phosphorylation of ERK1/2 and AKT. These results suggest that selective inhibition of FAAH is likely to be beneficial for TBI treatment.

Indexed as

AmidohydrolasesAnimalsAnxietyBrainBrain InjuriesCaspase 3Disease Models, AnimalExtracellular Signal-Regulated MAP KinasesFatty Acid Amide HydrolasesMaleMemory DisordersMice, Inbred C57BLMotor ActivityNeuroimmunomodulationNeuroprotective AgentsPiperidinesAmidohydrolasesCasp3 protein, mouseCaspase 3Extracellular Signal-Regulated MAP KinasesFatty Acid Amide HydrolasesNeuroprotective AgentsPF 3845PiperidinesProto-Oncogene Proteins c-aktPyridinesReceptor, Cannabinoid, CB1Receptor, Cannabinoid, CB2AEAFAAH inhibitionInflammationNeuroprotectionTBI

Identifiers

PMID24937045
PMCPMC4437642
OpenAlexW1982946237

What OpenQuestion holds

Textmetadata
LicenceTDM
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.