Project description:Inflammation after injury of the central nervous system (CNS) is increasingly viewed as a therapeutic target. However, comparative studies in different CNS compartments are sparse. To date only few studies based on immunohistochemical data and all referring to mechanical injury have directly compared inflammation in different CNS compartments. These studies revealed that inflammation is more pronounced in spinal cord than in brain. Therefore, it is unclear whether concepts and treatments established in the cerebral cortex can be transferred to spinal cord lesions and vice versa or whether immunological treatments must be adapted to different CNS compartments. By use of transcriptomic and flow cytometry analysis of equally sized photothrombotically induced lesions in the cerebral cortex and the spinal cord, we could document an overall comparable inflammatory reaction and repair activity in brain and spinal cord between day 1 and day 7 after ischemia. However, remyelination was increased after cerebral versus spinal cord ischemia which is in line with increased remyelination in grey matter in previous analyses and was accompanied by microglia dominated inflammation opposed to monocytes/macrophages dominated inflammation after spinal cord ischemia. Interestingly remyelination could be reduced by microglia and not hematogenous macrophage depletion. Our results show that despite different cellular composition of the postischemic infiltrate the inflammatory response in cerebral cortex and spinal cord are comparable between day 1 and day 7. A striking difference was higher remyelination capacity in the cerebral cortex, which seems to be supported by microglia dominance.
Project description:Microglia are considered both pathogenic and protective during recovery from demyelination, but their precise role remains ill-defined. Here, using an inhibitor of colony stimulating factor 1 receptor (CSF1R), PLX5622, and mice infected with a neurotropic coronavirus (mouse hepatitis virus, strain JHMV), we show that depletion of microglia after clearance of virus infection resulted in impaired myelin repair and prolonged clinical disease. Microglia were required only during the early stages of remyelination. Notably, large deposits of extracellular vesiculated myelin and cellular debris were detected in the spinal cords of PLX5622-treated and not control mice, which correlated with decreased numbers of oligodendrocytes in demyelinating lesions in drug-treated mice. Further, gene expression analyses demonstrated differential expression of genes involved in myelin debris clearance, lipid and cholesterol recycling, and promotion of oligodendrocyte function. The results also demonstrate that microglial function could not be compensated by infiltrating macrophages. Together, these results demonstrate key roles for microglia in debris clearance and the initiation of remyelination following infection with a neurotropic coronavirus but are not necessary during later stages of remyelination.
Project description:profiling gene transcription in a mouse model of permanent focal cerebral ischemia that was induced by middle cerebral artery occlusion (MCAO)
Project description:We obtained the profiles of neuronal phosphoproteome after cerebral ischemia and reperfusion by isolating mice hippocampus. Hippocampus combined from either nine sham or nine focal cerebral ischemia 1.5 h and reperfusion 24 h (IR) mice were lysed, digested, labeled with different TMT tags, then pooled and analyzed by LC/LC-MS/MS. In total, we quantified 7,865 phosphopeptides,179 phosphorylation sites of 129 proteins were upregulated and 843 phosphorylation sites of 494 proteins were downregulated in hippocampus during cerebral ischemia 2 h compare with sham operation.
Project description:To reveal the effects of Buyang Huanwu Decoction on circRNA-miRNA-mRNA transcriptional network of rats with cerebral ischemia, explore its molecular mechanism for the treatment of cerebral ischemia.
Project description:To reveal the molecular signatures of XingNaoKaiQiao acupuncture on the Cerebral cortex of rats with cerebral ischemia/reperfusion injury, we performed bulk RNA sequencing.
Project description:To reveal the alterations of mRNA profile in cerebral ischemia-reperfusion injury in rat. The SD rats were used to established the middle cerebral artery occlusion and reperfusion (MCAO/R) model. RNA-seq were performed to identify differences in gene expression.
Project description:Background and Purpose: Long noncoding RNAs (lncRNAs) are an emerging class of genomic regulatory molecules reported in neurodevelopment and many diseases. Despite extensive studies have identified lncRNAs and discovered their functions in CNS diseases, the function of lncRNAs in ischemia stroke remains poorly understood. Method: Ischemia was induced by transient middle cerebral artery occlusion. Expression profiles of lncRNAs, miRNAs and mRNAs after ischemia stroke were obtained using high throughput sequencing technology. A correlation network was constructed to predict lncRNA functions. LncRNA-miRNA-mRNA network was constructed to discover ceRNAs. Results: 1924 novel lncRNAs were identified, indicating that the ischemia stroke has a complex effect on lncRNAs. The top 10 regulated lncRNAs was validated by qRT-PCR. We have also predicted function of lncRNAs, and subjected them to gene co-expression network analysis, revealing the involvement of lncRNAs in many important biological process including injury and repair that are implicated in the regulation of ischemia stroke. Furthermore, lncRNAs mediated SMD (Staufen1-mediated mRNA decay) was analyzed and ceRNA (competitive endogenous RNAs) network was constructed in ischemia stroke. Conclusions: This study reports the genome-wide lncRNA profiles in ischemia stroke using high throughput sequencing and constructs a systematic lncRNA-miRNA-mRNA network which reveals a complex functional noncoding RNA regulatory network in ischemia stroke.
Project description:The transcriptomes of focal region in C57BL/6 mice after photothrombotic cerebral ischemia stroke generated by RNA-sequencing, using Illumina
Project description:This project included a normal control group, a model group, a cerebral ischemia group, and an acylcarnitine group, using ICR mice, and the mice were modeled for cerebral ischemia, and their brain tissues were taken to perform proteome analysis against ischemic stroke