Anti-Inflammatory and Antioxidant Effects of ω-3 Polyunsaturated Fatty Acids on Astrocytes and Their Implications for the Blood–Brain Barrier’s Integrity and Function

TL;DR

This paper reviews how ω-3 fatty acids reduce inflammation and protect the blood-brain barrier by modulating astrocyte activity.

Contribution

The paper highlights novel mechanisms by which ω-3 PUFAs preserve BBB integrity through astrocyte phenotype modulation.

Findings

ω-3 PUFAs suppress astrocyte activation and promote a protective A2 phenotype.

They activate Nrf2/ARE and Wnt/β-catenin pathways while inhibiting NF-κB and JAK/STAT3.

These effects help maintain blood-brain barrier function during inflammation.

Abstract

Impaired blood–brain barrier (BBB) integrity is a common hallmark of neurological disorders associated with neuroinflammation, neurodegeneration and aging. The function of the BBB relies heavily on the interaction between astrocytes and endothelial cells, the most closely connected elements of the neurovascular unit. Under inflammatory conditions, astrocytes can undergo a range of metabolic changes, becoming pro-inflammatory and harmful to endothelial cells. Upon activation, astrocytes secrete a plethora of inflammatory mediators that severely disrupt the barrier function of the BBB. ω-3 polyunsaturated fatty acids (PUFAs), mainly docosahexaenoic and eicosapentaenoic acids, exhibit protective anti-inflammatory and antioxidant effects demonstrated in various neurological disorders. This review focused on the role of ω-3 PUFAs and their oxidative derivatives, specialized pro-resolving mediators, in preserving the BBB’s integrity via suppression of astrocytes’ activation or even promotion of their transition from an A1 to an A2 phenotype. We considered mainstream mechanisms of the anti-inflammatory and antioxidant effects of ω-3 PUFAs on reactive astrocytes, such as stimulation of the Nrf2/ARE and Wnt/β-catenin signaling pathways, inhibition of NF-κB/matrix metalloproteinase activity and the JAK/STAT3 signaling axis, as well as the contribution of ω-3 PUFA-activated GPCRs and PPAR transcriptional factors, particularly regarding the role of these mechanisms in preserving the BBB’s integrity.

Figures