Interactions Among Nerve Regeneration, Angiogenesis, and the Immune Response Immediately After Sciatic Nerve Crush Injury in Sprague-Dawley Rats

Abstract

To preliminarily explore the primary changes in the expression of genes involved in peripheral nerve processes, namely, regeneration, angiogenesis, and the immune response, and to identify important molecular therapeutic targets, 45 Sprague-Dawley (SD) rats were randomly divided into a control group and an injury group. In the injury group, tissue samples were collected at 4 and 7 days after the injury for next-generation sequencing (NGS) analysis combined with gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and Venn diagram construction to identify the differentially expressed mRNAs (DEmRNAs) associated with regeneration, angiogenesis, and the immune response of the nerve. The expression of genes in the distal and proximal ends of the injured nerve after injury was analyzed by qRT-PCR. NGS revealed that compared with the control group, the injury group had 4020 DEmRNAs 4 days after injury and 3278 DEmRNAs 7 days after injury. A bioinformatics analysis showed that C-C chemokine receptor type 5 (CCR5), Thy1 cell surface antigen (Thy1), Notch homolog 1 (Notch1), and semaphorin 4A (Sema4A) were all associated with regeneration, angiogenesis, and the immune response of the nerve at both 4 and 7 days after injury, but qPCR revealed no significant difference in the expression of Thy1 (P = 0.29) or Sema4A (P = 0.82) in the proximal end, whereas a significant difference was observed in CCR5 and Notch1 (P < 0.05). The trend in the Notch1 change was basically consistent with the RNA-seq result after injury, which implied its indispensable role during endothelial cell proliferation and migration, macrophage recruitment, and neurotrophic factor secretion.

The basolateral amygdala-anterior cingulate pathway contributes to depression-like behaviors and comorbidity with chronic pain behaviors in male mice

“…Here, using gene-network theory, we prioritized Sema4a as one of the most prominently upregulated genes in a myelin-enriched gene module strongly affected by BLA–ACC activation. Previous reports had shown that increased Sema4a function contributes to the broad loss of mature oligodendrocytes and demyelination observed in neurological and autoimmune disorders, such as multiple sclerosis 55 – 58 , 78 . Our results extend these findings in the context of mood regulation, and involve a milder and possibly more localized dysregulation of Sema4a within the ACC.…”

The basolateral amygdala-anterior cingulate pathway contributes to depression and its comorbidity with chronic pain

“…Here, using gene network theory, we prioritized Sema4a as one of the most prominently upregulated genes in a myelin-enriched gene module strongly affected by BLA-ACC activation. Previous reports have shown that increased Sema4a function contributes to the broad and profound loss of mature oligodendrocytes and demyelination observed in neurological and autoimmune disorders, such as multiple sclerosis [52][53][54][55]72 . Our results extend these findings to a milder and more localized dysregulation of Sema4a signaling in the ACC, in the context of mood regulation.…”

Cysteine–Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice

“…Furthermore, CCR5 has been correlated with obesity, adipose tissue inflammation, and insulin resistance in both animal and human studies [ 18 , 19 ], and acute exercise may upregulate CCR5 expression in the skeletal muscles of patients with PCOS [ 20 ]. A recent study also revealed that CCR5 is associated with the regeneration, angiogenesis, and immune response of nerves from four to seven days after injury [ 21 ]. Further, the autosomal recessive deficiencies of CCR5 underlie resistance to HIV-1 [ 22 ].…”