Abstract:Traumatic brain injury (TBI) is a kind of disease with high morbidity, mortality, and disability, and its pathogenesis is still unclear. Research shows that nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) activation in neurons and astrocytes is involved in neuroinflammatory cascades after TBI. What is more, polydatin (PD) has been shown to have a protective effect on TBI-induced neuroinflammation, but the mechanisms remain unclear. Here, we speculated that PD could all… Show more
“…This suggests that SIRT1 inhibits value addition and phenotypic transformation of microglia, thereby reducing the enhancement in SAE. NLRP3 can worsen brain injury by causing neuroinflammation and damaging mitochondria (137). NLRP3 becomes activated during SAE through a multi-pathway mechanism, and it can affect the progression of SAE by promoting microglial activation.…”
Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis, which is characterized by cognitive dysfunction, a poor prognosis, and high incidences of morbidity and mortality. Substantial levels of systemic inflammatory factors induce neuroinflammatory responses during sepsis, ultimately disrupting the central nervous system's (CNS) homeostasis. This disruption results in brain dysfunction through various underlying mechanisms, contributing further to SAE’s development. Microglia, the most important macrophage in the CNS, can induce neuroinflammatory responses, brain tissue injury, and neuronal dysregulation, resulting in brain dysfunction. They serve an important regulatory role in CNS homeostasis and can be activated through multiple pathways. Consequently, activated microglia are involved in several pathogenic mechanisms related to SAE and play a crucial role in its development. This article discusses the role of microglia in neuroinflammation, dysfunction of neurotransmitters, disruption of the blood-brain barrier (BBB), abnormal control of cerebral blood flow, mitochondrial dysfunction, and reduction in the number of good bacteria in the gut as main pathogenic mechanisms of SAE, and focuses on studies targeting microglia to ameliorate SAE to provide a theoretical basis for targeted microglial therapy for SAE.
“…This suggests that SIRT1 inhibits value addition and phenotypic transformation of microglia, thereby reducing the enhancement in SAE. NLRP3 can worsen brain injury by causing neuroinflammation and damaging mitochondria (137). NLRP3 becomes activated during SAE through a multi-pathway mechanism, and it can affect the progression of SAE by promoting microglial activation.…”
Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis, which is characterized by cognitive dysfunction, a poor prognosis, and high incidences of morbidity and mortality. Substantial levels of systemic inflammatory factors induce neuroinflammatory responses during sepsis, ultimately disrupting the central nervous system's (CNS) homeostasis. This disruption results in brain dysfunction through various underlying mechanisms, contributing further to SAE’s development. Microglia, the most important macrophage in the CNS, can induce neuroinflammatory responses, brain tissue injury, and neuronal dysregulation, resulting in brain dysfunction. They serve an important regulatory role in CNS homeostasis and can be activated through multiple pathways. Consequently, activated microglia are involved in several pathogenic mechanisms related to SAE and play a crucial role in its development. This article discusses the role of microglia in neuroinflammation, dysfunction of neurotransmitters, disruption of the blood-brain barrier (BBB), abnormal control of cerebral blood flow, mitochondrial dysfunction, and reduction in the number of good bacteria in the gut as main pathogenic mechanisms of SAE, and focuses on studies targeting microglia to ameliorate SAE to provide a theoretical basis for targeted microglial therapy for SAE.
Spinal cord injury (SCI) is one of the most devastating central lesions, and mitochondrial function plays an important role in secondary injury after SCI. Polydatin (PD) is a natural glycosylated precursor of resveratrol, showing mitochondrial preservation effects in the central nervous system. This study aimed to identify the hub target genes of PD on mitochondrial membrane potential (MMP) in SCI. A comprehensive analysis was performed on SCI-related genes, MMP-related genes, and PD targets screening from public databases. Differential expression analysis was conducted to identify differentially expressed genes (DEGs) in SCI. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were employed to assess pathway enrichment. Protein-protein interaction (PPI) network analysis and molecular docking were conducted to identify key genes and evaluate the binding affinity between PD and hub genes. A total of 16,958 SCI-related genes, 2,786 MMP-related genes, 318 PD-related target genes, and 7229 DEGs were identified. Intersection analysis revealed 46 genes common to all four categories. GSEA and GSVA analysis identified significant enrichment of pathways associated with suppressed and activated SCI biological processes. The PPI network analysis identified seven core hub genes: <i>EGFR, SRC, VEGFA, STAT3, ERBB2, TP53,</i> and <i>RHOA.</i> Molecular docking revealed strong binding affinities between PD and <i>ERBB2, EGFR</i>, and <i>RHOA</i>. The findings based on computational investigation from public databases suggest that PD may have therapeutic potential for SCI by modulating MMP. These results contribute to the understanding of SCI pathogenesis and the development of novel therapeutic strategies.
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