Omega-3 fatty acids and acute neurological trauma: a perspective on clinical translation

Abstract

Acute neurological trauma remains one of the clinical areas with the most significant unmet needs worldwide. In the central nervous system, acute trauma has two stages: the primary injury and the secondary injury. The former is irreversible, and is a direct consequence of the impact. In the aftermath of the injury, a complex series of processes exacerbate the injury and amplify tissue damage. Some of these processes are local, others involve a systemic response. It is these processes which ultimately determine the clinical outcome. The aim of the treatments is a) to confer neuroprotection and b) to promote neuroregeneration. The results reported so far with omega-3 fatty acids in animal models of neurotrauma suggest that these compounds have the potential to offer a novel therapeutic approach and target both protection and regeneration. They lead to increased neuronal and glial survival, they can limit the damaging neuroinflammation and they can also protect neurites. Long chain omega-3 fatty acids such as eicosapentaenoic acid and docosahexaenoic acid have a complex pharmacodynamics, which leads potentially to the activation of a multitude of targets, including voltage and ligand-gated ion channels, transcription factors and G-protein coupled receptors. They can produce tissue-specific metabolites which have intrinsic activity, either on the same or on different cellular targets. The apparent large therapeutic window of omega-3 fatty acids is an advantage in the context of trauma, with patients in an unstable state, with multiple injuries. The specific use of omega-3 fatty acids in spinal cord injury and peripheral nerve injury will be discussed, focusing on issues which need to be addressed in order to translate successfully to the clinic the efficacy reported in the initial proof of concept animal studies.