Brain-Targeting Form of Docosahexaenoic Acid for Experimental Stroke Treatment: MRI Evaluation and Anti-Oxidant Impact

Abstract

Epidemiologic studies report cardiovascular protection conferred by omega-3 fatty acids, in particular docosahexaenoic acid (DHA). However, few experimental studies have addressed its potential in acute stroke treatment. The present study used multimodal MRI to assess in vivo the neuroprotection conferred by DHA and by a brain-targeting form of DHA-containing lysophosphatidylcholine (AceDoPC) in experimental stroke. Rats underwent intraluminal middle cerebral artery occlusion (MCAO) and were treated at reperfusion by intravenous injection of i) saline, ii) plasma from donor rats, iii) DHA or iv) AceDoPC, both solubilized in plasma. Twenty-four hours after reperfusion, animals underwent behavioral tests and were sacrificed. Multiparametric MRI (MRA, DWI, PWI, T2-WI) was performed at H0, during occlusion, and at H24, before sacrifice. Brain tissue was used for assay of F(2)-isoprostanes as lipid peroxidation markers. Initial lesion size and PWI/DWI mismatch were comparable in the four groups. Between H0 and H24, lesion size increased in the saline group (mean ± s.d.: +18% ± 20%), was stable in the plasma group (-3% ± 29%), and decreased in the DHA (-17% ± 15%, P=0.001 compared to saline) and AceDoPC (-34% ± 27%, P=0.001 compared to saline) groups. Neuroscores in the AceDoPC group tended to be lower than in the other groups (P=0.07). Treatments (pooled DHA and AceDoPC groups) significantly decreased lipid peroxidation as compared to controls (pooled saline and vehicle) (P=0.03). MRI-based assessment demonstrated the neuroprotective effect of DHA in the MCAO model. Results further highlighted the therapeutic potential of engineered brain-targeting forms of omega-3 fatty acids for acute stroke treatment.

Dietary Omega-6/Omega-3 and Endocannabinoids: Implications for Brain Health and Diseases

“…A possibility to bypass this issue would be to accelerate the bioavailability of PUFAs to the brain, by direct injection of free or esterified PUFAs into the brain. A preclinical study in rat demonstrated that an injection of DHA can reduce seizure score within one hour or one day, where three months are needed to reach the same result through the diet [167][168][169]. These promising results could be applied in the future to humans to reduce damages following stroke or reduce seizure events, but further investigations are needed before such clinical trials.…”

AceDoPC, a structured phospholipid to target the brain with docosahexaenoic acid

“…When pooling the DHA and AceDoPC r groups it appeared that a significant lowering of oxidative stress occurred, although this was not significant for each group alone. However, the values in the AceDoPC r group were lower than in D102, page 2 of 3 the DHA group (Chauveau et al, 2011). Altogether, these results show that AceDoPC r was more efficient than nonesterified DHA to protect the brain in a post-stroke situation.…”

“…Each rat was injected with one micromole of either DHA, or AceDoPC (both bound to rat plasma), as compared to the vehicle (rat plasma), or saline, one hour after stroke induction. The post-stroke brain lesions, assessed by magnetic resonance imaging, significantly decreased in both the DHA and AceDoPC r groups, compared to controls, but such a decrease was higher in the AceDoPC r group (Chauveau et al, 2011).…”

Specific uptake of DHA by the brain from a structured phospholipid, AceDoPC®

“…The lesion sizes due to the initial stroke were stable in rats receiving the plasma alone as a control, while they decreased in rats receiving nonesterified DHA or AceDoPC ® , the decrease being higher in rats receiving AceDoPC ® . Neuroscores also tended to be improved in the AceDoPC ® group (Chauveau et al, 2011). The mechanism of neuroprotection observed remains to be clarified but a reduction of oxidative stress has been suggested.…”