Omega-3 Polyunsaturated Fatty Acids Protect Neurological Function After Traumatic Brain Injury by Suppressing Microglial Transformation to the Proinflammatory Phenotype and Activating Exosomal NGF/TrkA Signaling

Abstract

The transformation of microglia to a pro-in ammatory phenotype at the site of traumatic brain injury (TBI) drives the progression of secondary neurodegeneration and irreversible neurological impairment.Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to suppress this phenotype transformation, thereby reducing neuroin ammation following TBI, but the molecular mechanisms are unknown. We found that Omega-3 PUFA suppressed the expression of disintegrin metalloproteinase (ADAM17), the enzyme required to convert tumor necrosis factor-a (TNF-α) to the soluble form, thereby inhibiting the TNF-α/NF-κB pathway both in vitro and in a mouse model of TBI. Omega-3 PUFA also prevented the reactive transformation of microglia and promoted the secretion of microglial exosomes containing nerve growth factor (NGF), activating the neuroprotective NGF/TrkA pathway both in culture and TBI model mice. Moreover, Omega-3 PUFA suppressed the pro-apoptotic NGF/P75NTR pathway at the TBI site and reduced apoptotic neuronal death, brain edema, and disruption of the blood-brain barrier. Finally, Omega-3 PUFA preserved sensory and motor function as assessed by two broad-spectrum test batteries. The bene cial effects of Omega-3 PUFA were blocked by an ADAM17 promotor and by a NGF inhibitor, con rming the pathogenic function of ADAM17 and the central neuroprotective role of NGF.Collectively, these ndings provide a strong experimental basis for Omega-3 PUFA as a potential clinical treatment for TBI.

Conservative Management of Acute Sports-Related Concussions: A Narrative Review

“…Other nutraceuticals that have been shown to significantly decrease CGRP in human trials for migraines include melatonin [133] and curcumin (turmeric) [134]. Preclinical data show that omega oils prevent the neuroinflammatory changes in microglia to a pro-inflammatory phenotype, activate neuroprotective cytokines, and mitigate TBIrelated blood-brain barrier disruption [135,136].…”