BackgroundTraumatic brain injury (TBI) is a critical public health and socioeconomic problem throughout the world. Inflammation-induced secondary injury is one of the vital pathogenic parameters of TBI. Molecular signaling cascades of pyroptosis, a specific type of cellular necrosis, are key drivers of TBI-induced inflammation.MethodsIn this study, mice with genetically ablated caspase-1 (caspase-1−/−) were subjected to controlled cortical impact injury in vivo, and primary neuron deficient in caspase-1 through siRNA knockdown and pharmacologic inhibition was stimulated by mechanical scratch, equiaxial stretch, and LPS/ATP in vitro. We evaluated the effects of caspase-1 deficiency on neurological deficits, inflammatory factors, histopathology, cell apoptosis, and pyroptosis.ResultsDuring the acute post-injury period (0–48 h) in vivo, motor deficits, anti-inflammatory cytokines (TGF-β and IL-10), pro-inflammatory cytokines (IFN-γ, IL-1β, and IL-18), and blood lactate dehydrogenase (LDH), as well as pyroptosis-related proteins (caspase-1, caspase-1 fragments, caspase-11 and GSDMD), were increased. Caspase-1 was activated in the cortex of TBI mice. Inflammatory activation was more profound in injured wild-type mice than in caspase-1−/− mice. In vitro, mechanical scratch, equiaxial stretch, and LPS/ATP-induced neuron pyroptosis, apoptosis, LDH release, and increased expression of inflammatory factors. The effects of mechanical and inflammatory stress were reduced through inhibition of caspase-1 activity through siRNA knockdown and pharmacologic inhibition.ConclusionCollectively, these data demonstrate that pyroptosis is involved in neuroinflammation and neuronal injury after TBI, and ablation of caspase-1 inhibits TBI-induced pyroptosis. Our findings suggest that caspase-1 may be a potential target for TBI therapy.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1083-y) contains supplementary material, which is available to authorized users.
Glial fibrillary acidic protein (GFAP) is one of the best markers for the activation of astrocytes (AS) following injury or stress in the central nervous system (CNS). The purpose of this study was to examine the expression of GFAP and 14-3-3ε in rat AS subjected to hypoxia. We established primary cultures of AS from cerebral cortex of neonatal Sprague-Dawley rats as a model of glucose deficiency and hypoxia/ischemia-reperfusion. We analyzed the activated astrocyte markers GFAP and 14-3-3ε by western blot analysis and found that both increased over time, starting at 4 h and reaching the highest level at 72 h, at the end of the experiment. GFAP and 14-3-3ε protein localization by double-labeling immunofluorescence showed elevated expression and co-localization in the cytoplasm of AS. GFAP and 14-3-3ε expression remained elevated in AS 72 h after stress conditions, which is possibly related to the excessive activation and dysfunction of the CNS in chronic injuries.
The lower lumbar motion segments L4-5 and L5-S1 showed larger AP and PD translations, respectively, than the higher vertebral motion segments during the weight-lifting motion. The data provide insight into the physiological motion characteristics of the lumbar spine and potential mechanical mechanisms of lumbar disease development.
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