Abstract:

Acquired neurological injuries initiate a pathological cascade of secondary injury processes, including inflammation, which continue for days to weeks following injury. Injury-induced neuroinflammation acts as a host defense mechanism contributing to the neutralization of the insult (removing offending factors) and restoring structure and function of the brain (establish homeostasis). The timing of these protective functions of the immune response is vital, since chronic inflammation has been associated with progressive cell loss and neurotoxicity. A separate sub-class of lipid mediators, termed specialized pro-resolving mediators (SPMs), functions to resolve inflammation. Endogenous SPMs, notably those derived from omega-3 fatty acids, may represent a valuable target in shifting the balance of neuroinflammatory processes from inflammation-driving to inflammation-resolving conditions in the injured CNS. Enthusiasm for a therapeutic approach involving SPMs comes from the natural routes of administration, such as dietary supplementation of their metabolic precursors, exogenous SPMs, and adjunctive interventions focused on increasing the availability of SPMs after injury. SPMs provide a cellular target for therapeutic approaches to limit secondary injury processes after acquired neurological injury. The potent anti-inflammatory properties of SPMs in peripheral diseases and the therapeutic efficacy of their fatty acid precursors in neurological disease provide a sound basis for further exploration of their neuroprotective efficacy in acquired neurological injury. Of particular value to the clinical problems of stroke and TBI are therapies which are rapid and accessible. The endogenous nature of SPMs makes them promising candidates for readily accessible therapies, which could shift the inflammatory balance toward resolution of cellular pathophysiology and limit the extent of injury.