ABSTRACT
To understand the effect of AMP-activated protein kinase (AMPK)-SIRT1 (silent information regulator 1)-PPARγ coactivator-1α (PGC1α) signaling pathway on the cognitive function of sevoflurane-anesthetized aged rats. Aged rats were divided into Normal group, Sevo group (Sevoflurane anesthesia), Sevo + AICAR (the AMPK activator) group, Sevo + EX527 group (the AMPK inhibitor), and Sevo + AICAR + EX527 group. The cognitive function of rats was determined by the Morris water maze. Hippocampal neuronal apoptosis was evaluated by TUNEL and Fluoro-Jade C (FJC) staining, and the expression of cleaved caspase-3 was detected by immunohistochemistry. ROS, SOD, and MDA levels and the fluorescence intensity of GFAP in the hippocampus were assayed. The mitochondrial membrane potential (MMP), mitochondrial mass, ATP level, and the expression of AMPK-SIRT1-PGC1α were determined by the corresponding methods. Rats in the Sevo group manifested significant extension in the escape latency, with fewer platform crossings; and meanwhile, the apoptotic rate, the number of FJC-positive cells, and the fluorescence intensity of GFAP of neurons were elevated, with up-regulation of cleaved caspase-3. Moreover, the level of MDA and ROS was increased evidently, with significant down-regulation of SOD activity, ATP, mitochondrial mass and MMP levels, and AMPK, SIRT1 and PGC-1α protein expressions. However, sevoflurane-induced changes above were improved after the administration of AICAR, and EX527 could reverse AICAR-induced improvements in Sevo-anesthetized aged rats. Activating AMPK-SIRT1-PGC1α pathway can improve the cognitive function and mitigate the neuronal injury in Sevo-anesthetized aged rats by antagonizing the oxidative stress and maintaining the mitochondrial function.
Subject(s)
Aging/physiology , Anesthetics, Inhalation/pharmacology , Cognition , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Protein Kinases/metabolism , Sevoflurane/pharmacology , Sirtuin 1/metabolism , AMP-Activated Protein Kinase Kinases , Aminoimidazole Carboxamide/analogs & derivatives , Aminoimidazole Carboxamide/pharmacology , Anesthetics, Inhalation/adverse effects , Animals , Apoptosis , Carbazoles/pharmacology , Hippocampus/drug effects , Hippocampus/growth & development , Hippocampus/metabolism , Hippocampus/physiology , Male , Membrane Potential, Mitochondrial , Oxidative Stress , Protein Kinase Inhibitors/pharmacology , Rats , Rats, Wistar , Ribonucleotides/pharmacology , Sevoflurane/adverse effects , Signal TransductionABSTRACT
OBJECTIVE: To explore the biomechanical effects on adjacent vertebra of thoracolumbar osteoporotic vertebral compression fracture (OVCF) after percutaneous kyphoplasty (PKP) with cement leakage into the disc by using finite element analysis. METHODS: T10-L2 segment data were obtained from computed tomography (CT) scans of an elder female with single T12 OVCF undergoing a cement leakage into the T12-L1 disc after PKP. A three-dimensional finite element Model of thoracolumbar spine (T10-L2) was built in the Mimics and the ABAQUS software. The stress on annulus fiber, nucleus pulposus, endplate and facet joints under axial pressure (0.3, 1.0, 4.0 MPa) were analyzed. RESULTS: The 3D finite element after percutaneous kyphoplasty (PKP) with cement leakage into the disc may be strongly related with the changes of biomechanical effects on adjacent vertebra of thoracolumbar OVCF. Models of thoracolumbar OVCF before and after PVP with a cement leakage into the T12-L1 disc were successfully established. The stresses increased with a rising axial pressure in the model of cement leakage into the disc after PVP, the stress augmentation scope on adjacent end plates(T11 low plate & L1 top plate) and intervertebral disc (T11-12 & T12-L1) increased. The maximal Von Mises stress on adjacent vertebra (T11 & L1) increased while but the maximal Von Mises stress on end vertebra (T10 & L2) decreased. CONCLUSION: Postoperative adjacent vertebral fracture.
Subject(s)
Bone Substitutes , Extravasation of Diagnostic and Therapeutic Materials , Fractures, Compression/surgery , Intervertebral Disc/pathology , Kyphoplasty , Spinal Fractures/surgery , Aged , Biomechanical Phenomena , Female , Finite Element Analysis , Fractures, Compression/etiology , Humans , Osteoporosis/complications , Spinal Fractures/etiologyABSTRACT
OBJECTIVE: To build a three-dimensional finite element model of thoracolumbar spine with osteoporotic vertebral compression fracture (OVCF) and analyze its biomechanical change. METHODS: The T10-L2 segment data were obtained from computed tomography (CT) scans of an elderly female with a single T12 OVCF. A three-dimensional finite element model of thoracolumbar spine was constructed with the MIMICS and ABAQUS software. The model was composed of bony vertebrae, articulating facets, intervertebral disc and associated ligaments. The basic stress analysis of T10-L2 motion segment was made for different material properties of bone, ligaments and facet joints contacting frictional property. The stress on the annulus fiber, nucleus pulposus, endplate and facet joints under axial pressure (0.3 MPa, 1.0 MPa, 4.0 MPa) were analyzed. RESULTS: A three-dimensional finite element model of human T12-L2 motion segment had 617468 elements. And the stress was higher in vertebral body than posterior structure. The distribution of pressure stresses in intervertebral disc was asymmetrical. The stress increased with a rising axial pressure. CONCLUSION: 3D finite element model of thoracolumbar OVCF and adjacent segments are successfully established. The results of stress analysis are both feasible and reliable.
