**5.1 DHA and endogenous neuroprotective signaling**

In addition to its function as a unique building block of cell membranes, DHA is also a precursor for docosanoids and other bioactive endogenous derivatives in the neural tissue [37]. The number of recently identified DHA derivatives in neural tissue is increasingly growing and includes neuroprotectin D1 (NPD1), synaptamide, endocannabinoid epoxides, and elovanoids [38–40]. Collectively, the potent bioactive properties of these DHA derivatives contribute to preservation of normal neuronal function, tissue homeostasis, and neuronal survival [37–41]. In addition, the DHA derivatives exert a range of potent neuroprotective properties that include inhibition of proinflammatory gene expression and leukocyte infiltration. A striking hallmark of the DHA derivatives is their ability to potentiate microglial polarization from a proinflammatory phenotype to a surveillance-repair state and reduce NF-kB-mediated expression of inflammatory cytokines in the brain. Moreover, DHA derivatives contribute to BBB integrity and are neurogenic and synaptogenic [38, 42]. Thus, the DHA derivatives seem to be key mediators of the resolution of inflammation and recovery of homeostasis in the CNS microenvironment.
