Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms
Ethyl pyruvate (EP) is protective in experimental models of many illnesses. This study investigates whether EP can protect against neonatal hypoxic-ischemic (H-I) brain injury. Pre-treatment with EP significantly reduced brain damage at 7 days post-H-I, with 50 mg/kg EP achieving over 50% recovery i...
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| Format: | Article |
| Language: | English |
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Elsevier
2010-03-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109003659 |
| _version_ | 1818417590842687488 |
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| author | Hongxia Shen Xiaoming Hu Can Liu Suping Wang Wenting Zhang Hui Gao R. Anne Stetler Yanqin Gao Jun Chen |
| author_facet | Hongxia Shen Xiaoming Hu Can Liu Suping Wang Wenting Zhang Hui Gao R. Anne Stetler Yanqin Gao Jun Chen |
| author_sort | Hongxia Shen |
| collection | DOAJ |
| description | Ethyl pyruvate (EP) is protective in experimental models of many illnesses. This study investigates whether EP can protect against neonatal hypoxic-ischemic (H-I) brain injury. Pre-treatment with EP significantly reduced brain damage at 7 days post-H-I, with 50 mg/kg EP achieving over 50% recovery in tissue loss compared to vehicle-treated animals. Delayed treatment with EP until 30 min after H-I was still neuroprotective. EP-afforded brain protection, together with neurological function improvement, was observed up to 2 months after H-I. We further demonstrated an inhibitory effect of EP on cell death, both in an in vivo model of H-I and in in vitro neuronal cultures subjected to OGD, by reducing calpain activation and calcium dysregulation. Moreover, EP exerted an anti-inflammatory effect in microglia by inhibiting NF-κB activation and subsequent release of inflammatory mediators. Taken together, our results suggest that EP confers potent neuroprotection against neonatal H-I brain injury via its anti-cell death and anti-inflammatory actions. EP is a potential novel therapeutic agent for neonatal H-I brain injury. |
| first_indexed | 2024-12-14T12:09:12Z |
| format | Article |
| id | doaj.art-77fc890b98b840489a5c0b2aa3939514 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-14T12:09:12Z |
| publishDate | 2010-03-01 |
| publisher | Elsevier |
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| series | Neurobiology of Disease |
| spelling | doaj.art-77fc890b98b840489a5c0b2aa39395142022-12-21T23:01:48ZengElsevierNeurobiology of Disease1095-953X2010-03-01373711722Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanismsHongxia Shen0Xiaoming Hu1Can Liu2Suping Wang3Wenting Zhang4Hui Gao5R. Anne Stetler6Yanqin Gao7Jun Chen8State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences Fudan University, Shanghai 200032, ChinaDepartment of Neurology, University of Pittsburgh School of Medicine Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center Veterans Affairs Pittsburgh Health Care System Pittsburgh, PA 15260, USAState Key Laboratory of Medical Neurobiology and Institute of Brain Sciences Fudan University, Shanghai 200032, ChinaDepartment of Neurology, University of Pittsburgh School of Medicine Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center Veterans Affairs Pittsburgh Health Care System Pittsburgh, PA 15260, USAState Key Laboratory of Medical Neurobiology and Institute of Brain Sciences Fudan University, Shanghai 200032, ChinaState Key Laboratory of Medical Neurobiology and Institute of Brain Sciences Fudan University, Shanghai 200032, ChinaDepartment of Neurology, University of Pittsburgh School of Medicine Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center Veterans Affairs Pittsburgh Health Care System Pittsburgh, PA 15260, USAState Key Laboratory of Medical Neurobiology and Institute of Brain Sciences Fudan University, Shanghai 200032, China; Department of Neurology, University of Pittsburgh School of Medicine Pittsburgh, PA 15213, USA; Corresponding authors. J. Chen is to be contacted at Department of Neurology, S-507, Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Y. Gao, State Key Laboratory of Medical Neurobiology, Fudan University School of Medicine, Shanghai 200032, China.State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences Fudan University, Shanghai 200032, China; Department of Neurology, University of Pittsburgh School of Medicine Pittsburgh, PA 15213, USA; Geriatric Research, Educational and Clinical Center Veterans Affairs Pittsburgh Health Care System Pittsburgh, PA 15260, USA; Corresponding authors. J. Chen is to be contacted at Department of Neurology, S-507, Biomedical Science Tower, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Y. Gao, State Key Laboratory of Medical Neurobiology, Fudan University School of Medicine, Shanghai 200032, China.Ethyl pyruvate (EP) is protective in experimental models of many illnesses. This study investigates whether EP can protect against neonatal hypoxic-ischemic (H-I) brain injury. Pre-treatment with EP significantly reduced brain damage at 7 days post-H-I, with 50 mg/kg EP achieving over 50% recovery in tissue loss compared to vehicle-treated animals. Delayed treatment with EP until 30 min after H-I was still neuroprotective. EP-afforded brain protection, together with neurological function improvement, was observed up to 2 months after H-I. We further demonstrated an inhibitory effect of EP on cell death, both in an in vivo model of H-I and in in vitro neuronal cultures subjected to OGD, by reducing calpain activation and calcium dysregulation. Moreover, EP exerted an anti-inflammatory effect in microglia by inhibiting NF-κB activation and subsequent release of inflammatory mediators. Taken together, our results suggest that EP confers potent neuroprotection against neonatal H-I brain injury via its anti-cell death and anti-inflammatory actions. EP is a potential novel therapeutic agent for neonatal H-I brain injury.http://www.sciencedirect.com/science/article/pii/S0969996109003659Neonatal hypoxia-ischemiaNeuroprotectionCell deathInflammationMicrogliaCalpain |
| spellingShingle | Hongxia Shen Xiaoming Hu Can Liu Suping Wang Wenting Zhang Hui Gao R. Anne Stetler Yanqin Gao Jun Chen Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms Neurobiology of Disease Neonatal hypoxia-ischemia Neuroprotection Cell death Inflammation Microglia Calpain |
| title | Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms |
| title_full | Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms |
| title_fullStr | Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms |
| title_full_unstemmed | Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms |
| title_short | Ethyl pyruvate protects against hypoxic-ischemic brain injury via anti-cell death and anti-inflammatory mechanisms |
| title_sort | ethyl pyruvate protects against hypoxic ischemic brain injury via anti cell death and anti inflammatory mechanisms |
| topic | Neonatal hypoxia-ischemia Neuroprotection Cell death Inflammation Microglia Calpain |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109003659 |
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