title: Combination of mild hypothermia with neuroprotectants has greater neuroprotective effects during oxygen-glucose deprivation and reoxygenation-mediated neuronal injury.
abstract: Co-treatment of neuroprotective reagents may improve the therapeutic efficacy of hypothermia in protecting neurons during ischemic stroke. This study aimed to find promising drugs that enhance the neuroprotective effect of mild hypothermia (MH). 26 candidate drugs were selected based on different targets. Primary cultured cortical neurons were exposed to oxygen-glucose deprivation and reoxygenation (OGD/R) to induce neuronal damage, followed by either single treatment (a drug or MH) or a combination of a drug and MH. Results showed that, compared with single treatment, combination of MH with brain derived neurotrophic factor, glibenclamide, dizocilpine, human urinary kallidinogenase or neuroglobin displayed higher proportion of neuronal cell viability. The latter three drugs also caused less apoptosis rate in combined treatment. Furthermore, co-treatment of those three drugs and MH decreased the level of reactive oxygen species (ROS) and intracellular calcium accumulation, as well as stabilized mitochondrial membrane potential (MMP), indicating the combined neuroprotective effects are probably via inhibiting mitochondrial apoptosis pathway. Taken together, the study suggests that combined treatment with hypothermia and certain neuroprotective reagents provide a better protection against OGD/R-induced neuronal injury.
authors.affiliation: 1] Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China [2] Department of Neurology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Gao
authors.affiliation: 1] Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China [2] Department of Neurology, the 421 Hospital, Guangzhou, Guangdong, P. R. China.
authors.forename: Jian-Ou
authors.initials: JO
authors.lastname: Huang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Hu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
authors.forename: Shu-Zhen
authors.initials: SZ
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
authors.forename: Kai-Bin
authors.initials: KB
authors.lastname: Huang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, P. R. China.
authors.forename: Su-Yue
authors.initials: SY
authors.lastname: Pan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003080:Cold Temperature; D003131:Combined Modality Therapy; D003470:Culture Media / Q000737:chemistry; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D005914:Globins / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency; D007610:Kallikreins / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D000078787:Neuroglobin; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015427:Reperfusion Injury / Q000628:therapy
chemical_list: D003470:Culture Media; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D016291:Dizocilpine Maleate; D005914:Globins; D007610:Kallikreins; D005947:Glucose; D010100:Oxygen; D002118:Calcium