Mild hypothermia protects hippocampal neurons from oxygen-glucose deprivation injury through inhibiting caspase-3 activation |
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| Institution: | 1. Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China;2. Hospital of South China Agricultural University, Guangzhou, China;3. The Eastern Hospital of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;4. Zengcheng District People''s Hospital of Guangzhou, Guangzhou, China;1. University of Medicine and Pharmacy, Craiova, Romania;2. Department of Psychiatry, Aging & Psychiatric Disorders Group, University of Medicine Rostock, Germany;3. Division of Physiology and Fundamental Neuroscience, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania;4. Neuroscience and Pharmacology, Panum, University of Copenhagen, Copenhagen, Denmark;1. Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan;2. Department of Orthopaedic Surgery, Kobe Kaisei Hospital, Kobe, Japan;3. Human and Artificial Intelligent Systems, University of Fukui Graduate School of Engineering, Fukui, Japan;1. SDSU/UCSD Joint Doctoral Program in Clinical Psychology, 6330 Alvarado Court, Ste. 103, San Diego, CA 92120-4913, USA;2. Department of Cognitive Science, University of California, San Diego, La Jolla, CA 92093-0515, USA;3. Department of Radiology, University of California School of Medicine, San Diego, 200 West Arbor Drive, San Diego, CA 92103-8224, USA;4. Departments of Neurology, Child & Adolescent Psychiatry, New York University Langone Medical Center, 577 First Avenue, New York, NY 10016, USA;5. Department of Neurology, University of California School of Medicine, San Diego, La Jolla, CA 92093-0935, USA;6. Center for Human Development, University of California, San Diego, La Jolla, CA 92093-0115, USA;1. Department of Physiology, Kangwon National University School of Medicine, Chuncheon 200-701, South Korea;2. Department of Immunology, Lab of Dendritic Cell Differentiation and Regulation, College of Medicine, Konkuk University, Chungju 380-701, South Korea;3. Department of Biomedical Engineering, and Center for Marine-Integrated Biomedical Technology (BK21 Plus), Pukyong National University, Busan 608-737, South Korea;4. Department of Bio-health Technology, Kangwon National University, Chuncheon 200-701, South Korea;5. Department of Microbiology, Inje University College of Medicine, Busan 614-735, South Korea |
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| Abstract: | Mild hypothermia (MH) is thought to be one of the most effective therapeutic methods to treat hypoxic-ischemic encephalopathy (HIE) after cardiac arrest (CA). However, its precise mechanisms remain unclear. In this research, hippocampal neurons were cultured and treated with mild hypothermia and Ac-DEVD-CHO after oxygen-glucose deprivation (OGD). The activity of caspase-3 was detected, in order to find the precise concentration of Ac-DEVD-CHO with the same protective role in OGD injury as MH treatment. Western blot and immunofluorescence staining were conducted to analyze the effects of MH and Ac-DEVD-CHO on the expressions of caspase-3, caspase-8, and PARP. The neuronal morphology was observed with an optical microscope. The lactic acid dehydrogenase (LDH) release rate, neuronal viability, and apoptotic rate were also detected. We found that MH (32 °C) and Ac-DEVD-CHO (5.96 μMol/L) had equal effects on blocking the activation of caspase-3 and the OGD-induced cleavage of PARP, but neither had any effect on the activation of caspase-8, which goes on to activate caspase-3 in the apoptotic pathway. Meanwhile, both MH and Ac-DEVD-CHO had similar effects in protecting cell morphology, reducing LDH release, and inhibiting OGD-induced apoptosis in neurons. They also similarly improved neuronal viability after OGD. In conclusion, caspase-3 serves as a key intervention point of the key modulation site or regulatory region in MH treatment that protects neuronal apoptosis against OGD injury. Inhibiting the expression of caspase-3 had a protective effect against OGD injury in MH treatment, and caspase-3 activation could be applied to evaluate the neuroprotective effectiveness of MH on HIE. |
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| Keywords: | Mild hypothermia Ac-DEVD-CHO Oxygen-glucose deprivation Caspase-3 |
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