title: Protection against Oxygen-Glucose Deprivation/Reperfusion Injury in Cortical Neurons by Combining Omega-3 Polyunsaturated Acid with Lyciumbarbarum Polysaccharide.
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 Ca(2+) 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. zhe.shield@gmail.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. dierwu@gmail.com.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Cardiac Surgery II, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. jianpingyao@163.com.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Yao
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China. liliyao71@163.com.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. hzj609@163.com.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. pengli@umac.mo.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. jianbowan@umac.mo.
authors.forename: Jian-Bo
authors.initials: JB
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. chengweihe@umac.mo.
authors.forename: Chengwei
authors.initials: C
authors.lastname: He
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao 999078, China. huanxingsu@umac.mo.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Su
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency; D052139:Intracellular Calcium-Sensing Proteins / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D020813:Receptor, trkB / Q000187:drug effects; D015427:Reperfusion Injury / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy
chemical_list: D015820:Cadherins; D004365:Drugs, Chinese Herbal; D052139:Intracellular Calcium-Sensing Proteins; D018696:Neuroprotective Agents; C502406:fat1 protein, mouse; C500223:lycium barbarum polysaccharide; D004281:Docosahexaenoic Acids; D020813:Receptor, trkB; D005947:Glucose; D010100:Oxygen
keywords: Ca2+; DHA; LBP; OGD/R; Trk-B; cortical neurons; neuroprotection