Advanced MRI to assess hippocampal injury after incomplete cerebral ischemia-reperfusion in rats.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate advanced MRI findings in the bilateral hippocampus CA1 region of rats with hemorrhagic shock reperfusion (HSR) and their correlation with histopathological results. Additionally, this study aimed to identify effective MRI examination methods and detection indexes for assessing HSR. METHODS: Rats were randomized into the HSR and the Sham groups with 24 rats in each group. MRI examination included diffusion kurtosis imaging (DKI) and 3-dimensional arterial spin labeling (3D-ASL). Apoptosis and pyroptosis were evaluated directly from tissue. RESULTS: In the HSR group, cerebral blood flow (CBF) was significantly lower than that of the Sham group, while radial kurtosis (Kr), axial kurtosis (Ka), and mean kurtosis (MK) were all higher. In the HSR group, fractional anisotropy (FA) at 12 and 24 hours and radial diffusivity, axial diffusivity (Da), and mean diffusivity (MD) at 3 and 6 hours were lower than in the Sham group. MD and Da at 24 hours in the HSR group were significantly higher. The apoptosis rate and pyroptosis rate were also enhanced in the HSR group. CBF, FA, MK, Ka, and Kr values in the early stage were strongly correlated with apoptosis rate and pyroptosis rate. The metrics were obtained from DKI and 3D-ASL. CONCLUSIONS: Advanced MRI metrics from DKI and 3D-ASL, including CBF, FA, Ka, Kr, and MK values, are useful to evaluate abnormal blood perfusion and microstructural changes in the hippocampus CA1 area in the setting of incomplete cerebral ischemia-reperfusion in rats induced by HSR.

Identification of Osteosarcoma Metastasis-Associated Gene Biomarkers and Potentially Targeted Drugs Based on Bioinformatic and Experimental Analysis.

BACKGROUND: Metastasis is the leading cause of death for patients with osteosarcoma (OS). In the present study, we explore the biomarkers for metastatic OS and provide potential therapeutic approaches. MATERIALS AND METHODS: RNA-Seq data and clinical follow-up information were downloaded from TARGET and GEO databases. A Cox regression model was used to analyze metastatic events. L1000FWD, DGIdb, and CMap databases were used to identify potential drugs related to metastasis. Invasion and migration transwell assays and an adhesion assay were used to identify biological functions of genes. RESULTS: A total of 15 metastasis-related signatures (MRSs) were associated with the prognosis based on the TARGET or GSE21257 cohorts, among which IL10RA and TLR7 genes were especially significant. In the DGIdb drug-gene interaction database, TLR7 and IFNGR1 were found to have potential interactions with drugs. After inhibiting the expression of TLR7, the migration, invasion, and adhesion ability of OS cells were significantly enhanced, which further promoted metastasis. CONCLUSION: We identified a set of MRS that may be related to OS metastases. Among them, TLR7 plays a vital role and may be a potential target for OS metastasis treatment.

Exogenous carbon monoxide protects against mitochondrial DNA­induced hippocampal pyroptosis in a model of hemorrhagic shock and resuscitation.

Carbon monoxide­releasing molecule­3 (CORM­3), which is an exogenous carbon monoxide (CO) compound, slowly releases CO under physiological conditions; this exerts neuroprotective effects against incomplete ischemia/reperfusion injury. The objective of the present study was to investigate whether the administration of CORM­3 protects against nucleotide­binding oligomerization domain­like receptor pyrin domain­3 (NLRP3) inflammasome formation and neuronal pyroptosis in the hippocampus following hemorrhagic shock and resuscitation (HSR). To establish this, an HSR model was created. Hemorrhagic shock was induced in adult male Sprague­Dawley rats under sevoflurane anesthesia by bleeding using a heparinized syringe to maintain a mean arterial pressure of 30±5 mmHg for 60 min. Resuscitation was performed by reperfusion of the blood and, if necessary, administering sterile saline to achieve the baseline arterial pressure. Following resuscitation, CORM­3 (4 mg/kg) was injected via the femoral vein. Neuronal pyroptosis in the hippocampus, mitochondrial morphology, mitochondrial DNA (mtDNA), brain magnetic resonance imaging, expression levels of NLRP3 and the interaction of pro­caspase­1 and apoptosis­associated speck­like protein containing a CARD domain (ASC) were examined 12 h after HSR; locomotor activity was assessed 7 days after HSR. Compared with HSR­treated rats, CORM­3 administration resulted in a lower level of neuronal pyroptosis in the hippocampus, improved mitochondrial morphology, a lower mtDNA level, steadier levels of metabolites, decreased expression levels of NLRP3 and pro­caspase­1 interacting with ASC and enhanced locomotor activity. In conclusion, treatment with CORM­3 ameliorated impairments of locomotor and exploratory activities in a rat model of HSR. The mechanism may be associated with the inhibition of mitochondrial DNA­induced pyroptosis via improvements in cell metabolism.