title: 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.
abstract: 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.
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China.
authors: Chi
authors: C
authors: Zhang
authors: Department of Neurosurgery, 101th Hospital of PLA, Rescue Center of Craniocerebral Injuries of PLA, Wuxi, Jiangsu 214044, PR China.
authors: Jie
authors: J
authors: Zhu
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Lanzhou General Hospital of Lanzhou Military Command, Lanzhou, Gansu 730050, PR China.
authors: Jing
authors: J
authors: Zhang
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China.
authors: Haoyu
authors: H
authors: Li
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China.
authors: Zijin
authors: Z
authors: Zhao
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China.
authors: Yiwei
authors: Y
authors: Liao
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China.
authors: Xiangyu
authors: X
authors: Wang
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China.
authors: Jun
authors: J
authors: Su
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China.
authors: Shushan
authors: S
authors: Sang
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China. Electronic address: yuanxianruicsu@hotmail.com.
authors: Xianrui
authors: X
authors: Yuan
authors: Department of Neurosurgery, Xiangya Hospital, Central-South University, Changsha, Hunan 410008, PR China. Electronic address: liuqcsu@hotmail.com.
authors: Qing
authors: Q
authors: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001930:Brain Injuries / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014635:Valproic Acid / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D014635:Valproic Acid; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Akt; Extracellular signal-regulated kinase; Neuroprotective effect; Rat; Traumatic brain injury; Valproic acid