Neuroinflammation lipid mediators are bioactive lipid molecules derived from the enzymatic breakdown of membrane phospholipids that act as signaling molecules to initiate, propagate, or resolve the inflammatory response within the central nervous system. This class includes pro-inflammatory eicosanoids, such as prostaglandins and leukotrienes, and anti-inflammatory, pro-resolving mediators (SPMs), like resolvins and protectins. The balance between these opposing lipid signals dictates the trajectory of neuroinflammation and its impact on neuronal survival.
Origin
This term stems from the convergence of neuroimmunology and lipid biochemistry, defining the role of lipids in the brain’s immune response. The concept of ‘mediators’ emphasizes their active, signaling role in cellular communication. In the context of hormonal health, systemic endocrine signals, such as glucocorticoids and adipokines, significantly modulate the enzymatic pathways that produce these lipid mediators, thereby linking peripheral metabolic state to central nervous system inflammation.
Mechanism
The mechanism begins with the activation of phospholipase A2 (PLA2) in response to cellular stress, releasing arachidonic acid (AA) from membrane phospholipids. AA is then metabolized by cyclooxygenases (COX) and lipoxygenases (LOX) into pro-inflammatory eicosanoids that exacerbate inflammation. Conversely, omega-3 fatty acids are metabolized into specialized pro-resolving mediators (SPMs) that actively terminate the inflammatory response and promote tissue repair. The shift in the enzymatic balance between these two pathways determines whether neuroinflammation becomes chronic and damaging or is effectively resolved.
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