Abstract
Ischemic stroke, characterized by the disturbance of the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity. However, there is no effective pharmacotherapy for ischemic injury. Currently, combined treatment is highly recommended for this devastating injury. In the present study, we investigated neuroprotective effects of the combination of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) and Lyciumbarbarum polysaccharide (LBP) on cortical neurons using an in vitro ischemic model. Our study demonstrated that treatment with docosahexaenoic acid (DHA), a major component of the ω-3 PUFAs family, significantly inhibited the increase of intracellular Ca2+ in cultured wild type (WT) cortical neurons subjected to oxygen-glucose deprivation/reperfusion (OGD/R) injury and promoted their survival compared with the vehicle-treated control. The protective effects were further confirmed in cultured neurons with high endogenous ω-3 PUFAs that were isolated from fat-1 mice, in that a higher survival rate was found in fat-1 neurons compared with wild-type neurons after OGD/R injury. Our study also found that treatment with LBP (50 mg/L) activated Trk-B signaling in cortical neurons and significantly attenuated OGD/R-induced cell apoptosis compared with the control. Notably, both combining LBP treatment with ω-3 PUFAs administration to WT neurons and adding LBP to fat-1 neurons showed enhanced effects on protecting cortical neurons against OGD/R injury via concurrently regulating the intracellular calcium overload and neurotrophic pathway. The results of the study suggest that ω-3 PUFAs and LBP are promising candidates for combined pharmacotherapy for ischemic stroke.
Highlights
Ischemic stroke, characterized by the disturbance of the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity [1]
We investigated the neuroprotective effects of ω-3 PUFAs, Lyciumbarbarum polysaccharide (LBP) and the combination of ω-3 PUFAs and LBP on rescuing cortical neurons from oxygen-glucose deprivation/reperfusion (OGD/R) and determined their distinguishing mechanisms of action through activating Trk B receptor and reducing intracellular Ca2+ overload
Consistent with previous reports, the Fluo-4 fluorescence intensity was decreased by Intriguingly, our data demonstrated that combined use of LBP with exogenous docosahexaenoic acid (DHA) could further exogenous2+DHA treatment compared with wild type (WT) OGD/R neurons
Summary
Ischemic stroke, characterized by the disturbance of the blood supply to the brain, is a severe worldwide health threat with high mortality and morbidity [1]. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been demonstrated to elicit therapeutic effects in a variety of neurological disorders including ischemic stroke [5,6,7,8,9,10]. They are essential fatty acids for human beings, which can maintain cellular membrane structural and functional integrity. We investigated the neuroprotective effects of ω-3 PUFAs, LBP and the combination of ω-3 PUFAs and LBP on rescuing cortical neurons from OGD/R and determined their distinguishing mechanisms of action through activating Trk B receptor and reducing intracellular Ca2+ overload
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