Neuroprotective and anti-apoptotic effects of valproic acid on adult rat cerebral cortex through ERK and Akt signaling pathway at acute phase of traumatic brain injury
| Autor: | Jing Zhang, Haoyu Li, Jie Zhu, Shu-shan Sang, Yiwei Liao, Xianrui Yuan, Zijin Zhao, Jun Su, Qing Liu, Chi Zhang, Xiangyu Wang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
MAPK/ERK pathway Traumatic brain injury Apoptosis Pharmacology Neuroprotection Rats Sprague-Dawley chemistry.chemical_compound Animals Medicine LY294002 Extracellular Signal-Regulated MAP Kinases Molecular Biology Protein kinase B Cerebral Cortex Valproic Acid business.industry Akt/PKB signaling pathway General Neuroscience medicine.disease Rats Neuroprotective Agents chemistry Brain Injuries lipids (amino acids peptides and proteins) Neurology (clinical) Signal transduction business Proto-Oncogene Proteins c-akt Neuroscience Signal Transduction Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 1555:1-9 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2014.01.051 |
| Popis: | Mood stabilizer valproic acid (VPA), a widely used antiepileptic drug that has been demonstrated neuroprotective effect against various insults through multiple signaling pathways. The role of VPA in traumatic brain injury (TBI) remains unclear. In the present study, we investigated the neuroprotective potency of VPA for protection against TBI in adult rats, focusing on studying signaling mediators of two well characterized pro-survival molecules, extracellular signal-regulated protein kinase (ERK) and Akt. We found that treatment of VPA after TBI significantly attenuated brain edema, reduced contusion volume and the rate of neuronal apoptosis. The treatment also partly blocked an increase in capase-3 activity. VPA markedly up-regulated the activity of ERK and Akt expression. Moreover, treatment with either PD98059, an ERK inhibitor and/or LY294002, an Akt inhibitor, attenuated the neuroprotection of VPA against TBI to varying degrees. Taken together, these results demonstrated that treatment with VPA after TBI could be neuroprotective via activation of ERK and Akt signaling pathways. |
| Databáze: | OpenAIRE |
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