Intravenous Treatment with a Long-Chain Omega-3 Lipid Emulsion Provides Neuroprotection in a Murine Model of Ischemic Stroke – A Pilot Study

Abstract

Single long-chain omega-3 fatty acids (e.g. docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA)) are known for their neuroprotective properties associated with ischemic stroke. This pilot study aimed to test the effectiveness of an acute treatment with a long-chain omega-3 lipid emulsion (Omegaven 10%®, OGV) that contains fish oil (DHA 18 mg/ml; EPA 21 mg/ml) and α-tocopherol (0.2 mg/ml) in a transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in mice. For this purpose, female CD-1 mice were anesthetized and subjected to 90 minutes of MCAO. To reflect a clinically relevant situation for an acute treatment, either after induction of stroke or after reperfusion, a single dose of OGV was injected intravenously into the tail vein (5 ml/kg b.w.). A neurological severity score was used to assess motor function and neurological outcome. Stroke-related parameters were determined 24 hours after MCAO. Microdialysis was used to collect samples from extracellular space of the striatum. Mitochondrial function was determined in isolated mitochondria or dissociated brain cells. Inflammation markers were measured in brain homogenate. According to control experiments, neuroprotective effects could be attributed to the long-chain omega-3 content of the emulsion. Intravenous injection of OGV reduced size and severity of stroke, restored mitochondrial function, and prevented excitotoxic glutamate release. Increases of pro-inflammatory markers (COX-2 and IL-6) were attenuated. Neurological severity scoring and neurochemical data demonstrated that acute OGV treatment shortly after induction of stroke was most efficient and able to improve short-term neurological outcome, reflecting the importance of an acute treatment to improve the outcome. Summarising, acute treatment of stroke with a single intravenous dose of OGV provided strong neuroprotective effects and was most effective when given immediately after onset of ischemia. As OGV is an approved fishoil emulsion for parenteral nutrition in humans, our results may provide first translational data for a possible early management of ischemic stroke with administration of OGV to prevent further brain damage.

Lipid Emulsion Improves Functional Recovery in an Animal Model of Stroke

“…The protective roles of fatty acids have received much attention in studies regarding stroke. Different compositions of lipid emulsions, such as omega-3, have been reported to provide neuroprotection against ischemic stroke injuries [ 48 ]. Emulsions of n-3 fatty acids have been shown to effectively reduce infarction volume and inflammation in the ischemic brain in neonatal mice [ 49 ].…”

Aneurysmal Subarachnoid Hemorrhage and Resolution of Inflammation

“…The effects of omega-3 FAs (or specific derivatives) in neural tissue have been widely examined in experimental ischemiareperfusion models [55,68,69]. These studies have consistently shown that omega-3 FAs significantly reduce cerebral infarction volume by around 40-50% and are associated with a drastic decrease in the neuroinflammatory response [70,71]. Interestingly, the long-term neurobehavioral recovery in experimental models of ischemic stroke is associated with neuroprotective effects of DHA on both gray and white matter [55].…”

“…Interestingly, the long-term neurobehavioral recovery in experimental models of ischemic stroke is associated with neuroprotective effects of DHA on both gray and white matter [55]. It is noteworthy that one of these studies used a specific FOLE that is widely approved for clinical use [70].…”

Docosahexaenoic Acid has stem cell-specific effects in the SVZ and restores olfactory neurogenesis and function in the aging brain

“…DHA is important for normal brain development (for review see McCann and Ames, 2005;Heird and Lapillonne, 2005) and its deficiency has been found to result in loss of visual and cognitive abilities in rodents and humans (reviewed in McCann &Ames, 2005 andInnis, 2003). Conversely, dietary supplementation of DHA during infancy may improve cognitive development in humans (Birch et al 2000, Willatts et al, 1998 and may have preventative and ameliorative effects on cognitive function in aged, diseased (i.e., Alzheimer's and Parkinson's Diseases), or injured (i.e., stroke and traumatic brain injury) adult brain (reviewed in Johnson &Danquor, 2006;Arsenault et al, 2011;Calon, et al 2004, Bousquet, et al, 2011, Belayev et al, 2009Berressem et al, 2016, Bailes & Mills, 2010Wu et al, 2011). DHA has been implicated in age-related brain function because declines in both brain and blood DHA levels have been correlated with the onset of dementia and cognitive decline (Weiser, et al, 2016;Mohajeri et al, 2015;Yurko-Mauro, et al, 2010).…”