Introduction: The number of stroke patients arriving at hospital within a therapeutic timeframe is increasing, enabling earlier and more successful intervention with thrombolysis and thrombectomy. Despite promising animal data, no neuroprotectants have translated into clinical practice. Brain tissue contains a high amount of polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA), an omega-3 fatty acid essential for normal brain growth and cognitive function. As DHA plays a critical role in neuronal survival and synaptic function, and is also a potent modulator of brain inflammation, it is a strong candidate for a successful neuroprotectant in stroke.
Aims: We therefore aimed to summarise the current evidence for omega-3 fatty acids as a treatment for experimental acute ischaemic stroke.
Methods: A systematic literature review of papers reporting omega-3 administration in animal models of acute stroke was conducted using the CAMARADES systematic review facility (SyRF). 1173 titles were screened, 168 abstracts reviewed and data extracted from 15 studies. Data were extracted manually, and collated, organised and analysed within CAMARADES. Measures of study quality were recorded, reflecting current STAIR recommendations for pre-clinical studies. Pre-defined endpoints extracted included mortality, infarct volume and neurobehavioural score.
Results: DHA reduced infarct volume with an effect size of 48.5%, (95% CI 32.2 - 65.5) compared to control treatments. Neurobehavioural score was improved by 34.8%,( 95% CI 21.8 - 47.7) in DHA treated animals. There was a decrease in mortality of 61% for DHA treated animals (OR 0.39, 95% CI 0.21-0.77(12 studies, no heterogeneity)). All studies used male animals, and no studies co-administered alteplase. Composition of omega-3 preparations was a source of significant heterogeneity (P<0.05). Post hoc analysis showed laboratory group was also a significant source of heterogeneity.
Conclusions: Current evidence suggests that DHA administration significantly improves outcome and decreases mortality in animal models of acute ischaemic stroke, providing support for further translational studies.