Protective Effects of N-Oleoylglycine in a Mouse Model of Mild Traumatic Brain Injury

Fabiana Piscitelli*, Francesca Guida, Livio Luongo, Fabio Arturo Iannotti, Serena Boccella, Roberta Verde, Anna Lauritano, Roberta Imperatore, Reem Smoum, Luigia Cristino, Aron H. Lichtman, Linda A. Parker, Raphael Mechoulam, Sabatino Maione, Vincenzo Di Marzo

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Traumatic brain injury (TBI) is one of the main causes of death in young people for which currently no efficacious treatment exists. Recently, we have reported that mice with mild-TBI with a specific injury in the insula showed elevated levels of a little investigated N-acyl amino acid, N-oleoylglycine (OlGly). N-acyl amino acids have recently experienced an increased interest because of their important biological activities. They belong to the endocannabinoidome family of lipids with structural similarities with the endocannabinoids (eCBs). The aim of this study was to test the neuroprotective and antihyperalgesic actions of OlGly in a model of mouse mild-TBI (mTBI) and its effect on levels of eCBs and N-acylethanolamines at the end of treatment. Following mTBI, mice were administered a daily injection of OlGly (10-50-100 mg/kg i.p.) for 14 days. Treatment with OlGly normalized motor impairment and behavior in the light/dark box test, ameliorated TBI-induced thermal hyperalgesia and mechanical allodynia, and normalized aggressiveness and depression. Moreover, levels of eCBs and some N-acylethanolamines underwent significant changes 60 days after TBI, especially in the prefrontal cortex and hypothalamus, and OlGly reversed some of these changes. In conclusion, our findings reveal that OlGly ameliorates the behavioral alterations associated with mTBI in mice, while concomitantly modulating eCB and eCB-like mediator tone.

Original languageAmerican English
Pages (from-to)1117-1128
Number of pages12
JournalACS Chemical Neuroscience
Issue number8
StatePublished - 15 Apr 2020

Bibliographical note

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© 2020 American Chemical Society.


  • N-acylethanolamines
  • N-oleoylglycine
  • behavior
  • endocannabinoids
  • mTBI
  • neuroprotection


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