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.