title: PD98059 Protects Brain against Cells Death Resulting from ROS/ERK Activation in a Cardiac Arrest Rat Model.
abstract: The clinical and experimental postcardiac arrest treatment has not reached therapeutic success. The present study investigated the effect of PD98059 (PD) in rats subjected to cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). Experimental rats were divided randomly into 3 groups: sham, CA, and PD. The rats except for sham group were subjected to CA for 5 min followed by CPR operation. Once spontaneous circulation was restored, saline and PD were injected in CA and PD groups, respectively. The survival rates and neurologic deficit scores (NDS) were observed, and the following indices of brain tissue were evaluated: ROS, MDA, SOD, p-ERK1/2/ERK1/2, caspase-3, Bax, Bcl-2, TUNEL positive cells, and double fluorescent staining of p-ERK/TUNEL. Our results indicated that PD treatment significantly reduced apoptotic neurons and improved the survival rates and NDS. Moreover, PD markedly downregulated the ROS, MDA, p-ERK, and caspase-3, Bax and upregulated SOD and Bcl-2 levels. Double staining p-ERK/TUNEL in choroid plexus and cortex showed that cell death is dependent on ERK activation. The findings in present study demonstrated that PD provides neuroprotection via antioxidant activity and antiapoptosis in rats subjected to CA/CPR.
authors.affiliation: Department of Physiology, Pre-Clinical Science, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Phuong Anh
authors.initials: PA
authors.lastname: Nguyen Thi
authors.affiliation: Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Meng-Hua
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Nuo
authors.initials: N
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Diseases, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Zhuo
authors.affiliation: Department of Physiology, Pre-Clinical Science, Guangxi Medical University, Nanning, Guangxi 530021, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xie
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000494:pharmacology*; D006323:Heart Arrest / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D005419:Flavonoids; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one