title: Serine-threonine protein kinase activation may be an effective target for reducing neuronal apoptosis after spinal cord injury.
abstract: The signaling mechanisms underlying ischemia-induced nerve cell apoptosis are poorly understood. We investigated the effects of apoptosis-related signal transduction pathways following ischemic spinal cord injury, including extracellular signal-regulated kinase (ERK), serine-threonine protein kinase (Akt) and c-Jun N-terminal kinase (JNK) signaling pathways. We established a rat model of acute spinal cord injury by inserting a catheter balloon in the left subclavian artery for 25 minutes. Rat models exhibited notable hindlimb dysfunction. Apoptotic cells were abundant in the anterior horn and central canal of the spinal cord. The number of apoptotic neurons was highest 48 hours post injury. The expression of phosphorylated Akt (p-Akt) and phosphorylated ERK (p-ERK) increased immediately after reperfusion, peaked at 4 hours (p-Akt) or 2 hours (p-ERK), decreased at 12 hours, and then increased at 24 hours. Phosphorylated JNK expression reduced after reperfusion, increased at 12 hours to near normal levels, and then showed a downward trend at 24 hours. Pearson linear correlation analysis also demonstrated that the number of apoptotic cells negatively correlated with p-Akt expression. These findings suggest that activation of Akt may be a key contributing factor in the delay of neuronal apoptosis after spinal cord ischemia, particularly at the stage of reperfusion, and thus may be a target for neuronal protection and reduction of neuronal apoptosis after spinal cord injury.
authors.affiliation: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Mu
authors.initials: M
authors.lastname: Jin
authors.affiliation: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Wei-Ping
authors.identifier: 0000-0002-8948-5432
authors.initials: WP
authors.lastname: Cheng
authors.affiliation: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Jia-Kai
authors.identifier: 0000-0001-7737-8114
authors.initials: JK
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Si-Yu
authors.initials: SY
authors.lastname: Hou
authors.affiliation: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Xiu-Hua
authors.initials: XH
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China.
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Liu
keywords: c-Jun N-terminal kinase; cell apoptosis; extracellular signal-regulated kinase; ischemic spinal cord injury; nerve regeneration; neural regeneration; neurological function; serine-threonine protein kinase