Journal of neurotrauma
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Journal of neurotrauma · Apr 2022
Association between serum calcium level and hemorrhagic progression in patients with traumatic intraparenchymal hemorrhage: Investigating the mediation and interaction effects of coagulopathy.
In this study, we investigate the association of serum calcium with coagulopathy and hemorrhagic progression contusion (HPC) in patients with traumatic intraparenchymal hemorrhage (tIPH), and further explore the interaction and mediation effect between serum calcium and coagulopathy on HPC. We conducted retrospective analyses of patients with tIPH admitted to the First Affiliated Hospital of Wenzhou Medical University between January 2016 to December 2019. The clinical data, coagulation parameters, and serum calcium levels were collected for further analysis. ⋯ Moreover, comparable results were held using corrected calcium, as well. Admission serum calcium level is associated with the HPC for patients with tIPH and this relationship is partially mediated by coagulopathy, but no significant interaction is detected. Further studies are needed to validate the findings and explore its mechanisms.
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Journal of neurotrauma · Apr 2022
Dysfunctional ER-mitochondrion coupling is associated with ER stress-induced apoptosis and neurological deficits in a rodent model of severe head injury.
Cellular homeostasis requires critical communications between the endoplasmic reticulum (ER) and mitochondria to maintain the viability of cells. This communication is mediated and maintained by the mitochondria-associated membranes and may be disrupted during acute traumatic brain injury (TBI), leading to structural and functional damage of neurons and supporting cells. To test this hypothesis, we subjected male C57BL/6 mice to severe TBI (sTBI) using a controlled cortical impact device. ⋯ This enhanced coupling correlated closely with increases in the expression of the Ca2+ regulatory proteins (inositol 1,4,5-trisphosphate receptor type 1 [IP3R1], voltage-dependent anion channel 1 [VDAC1], glucose-regulated protein 75 [GRP75], Sigma 1 receptor [Sigma-1R]), production of ROS, degree of ER stress, levels of UPR, and release of proinflammatory cytokines. Further, the neurological function of sTBI mice was significantly improved by silencing the gene for the ER-mitochondrion tethering factor PACS2, restoring the IP3R1-GRP75-VDAC1 axis of Ca2+ regulation, alleviating mitochondria-derived oxidative stress, suppressing inflammatory response through the PERK/eIF2α/ATF4/CHOP pathway, and inhibiting ER stress and associated apoptosis. These results indicate that dysfunctional ER-mitochondrion coupling might be primarily involved in the neuronal apoptosis and neurological deficits, and modulating the ER-mitochondrion crosstalk might be a novel therapeutic strategy for sTBI.