Administration of palmitoylethanolamide (PEA) protects the neurovascular unit and reduces secondary injury after traumatic brain injury in mice

Akbar Ahmad, Rosalia Crupi, Daniela Impellizzeri, Michela Campolo, Angela Marino, Emanuela Esposito, Salvatore Cuzzocrea

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) is a major cause of preventable death and morbidity in young adults. This complex condition is characterized by significant blood brain barrier leakage that stems from cerebral ischemia, inflammation, and redox imbalances in the traumatic penumbra of the injured brain. Recovery of function after TBI is partly through neuronal plasticity. In order to test whether treatments that enhance plasticity might improve functional recovery, a controlled cortical impact (CCI) in adult mice, as a model of TBI, in which a controlled cortical impactor produced full thickness lesions of the forelimb region of the sensorimotor cortex, was performed. Once trauma has occurred, combating these exacerbations is the keystone of an effective TBI therapy. The endogenous fatty acid palmitoylethanolamide (PEA) is one of the members of N-acyl-ethanolamines family that maintain not only redox balance but also inhibit the mechanisms of secondary injury. Therefore, we tested whether PEA shows efficacy in a mice model of experimental TBI. PEA treatment is able to reduced edema and brain infractions as evidenced by decreased 2,3,5-triphenyltetrazolium chloride staining across brain sections. PEA-mediated improvements in tissues histology shown by reduction of lesion size and improvement in apoptosis level further support the efficacy of PEA therapy. The PEA treatment blocked infiltration of astrocytes and restored CCI-mediated reduced expression of PAR, nitrotyrosine, iNOS, chymase, tryptase, CD11b and GFAP. PEA inhibited the TBI-mediated decrease in the expression of pJNK and NF-κB. PEA-treated injured animals improved neurobehavioral functions as evaluated by behavioral tests.

Original languageEnglish (US)
Pages (from-to)1310-1321
Number of pages12
JournalBrain, Behavior, and Immunity
Volume26
Issue number8
DOIs
StatePublished - Nov 2012
Externally publishedYes

Fingerprint

Wounds and Injuries
Oxidation-Reduction
Ethanolamines
Chymases
Therapeutics
Tryptases
Neuronal Plasticity
Forelimb
palmidrol
Traumatic Brain Injury
Recovery of Function
Brain Edema
Brain
Brain Ischemia
Blood-Brain Barrier
Astrocytes
Young Adult
Cause of Death
Histology
Theoretical Models

Keywords

  • GFAP
  • Inflammation
  • Mast cells
  • PEA
  • Traumatic brain injury

ASJC Scopus subject areas

  • Immunology
  • Behavioral Neuroscience
  • Endocrine and Autonomic Systems

Cite this

Administration of palmitoylethanolamide (PEA) protects the neurovascular unit and reduces secondary injury after traumatic brain injury in mice. / Ahmad, Akbar; Crupi, Rosalia; Impellizzeri, Daniela; Campolo, Michela; Marino, Angela; Esposito, Emanuela; Cuzzocrea, Salvatore.

In: Brain, Behavior, and Immunity, Vol. 26, No. 8, 11.2012, p. 1310-1321.

Research output: Contribution to journalArticle

Ahmad, Akbar ; Crupi, Rosalia ; Impellizzeri, Daniela ; Campolo, Michela ; Marino, Angela ; Esposito, Emanuela ; Cuzzocrea, Salvatore. / Administration of palmitoylethanolamide (PEA) protects the neurovascular unit and reduces secondary injury after traumatic brain injury in mice. In: Brain, Behavior, and Immunity. 2012 ; Vol. 26, No. 8. pp. 1310-1321.
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