The Study on Neural Remodeling of Medullary Visceral Zone in Early Sepsis and Interfered by Cholinergic Anti-Inflammatory Pathway ​

BackgroundStudies including our own have shown that the Medullary Visceral Zone (MVZ) can effectively regulate systemic inflammation and immunity through the Cholinergic Anti-inflammatory Pathway (CAP). Sepsis usually causes neuroinflammation in the Central Nervous System (CNS), which will inevitably affect the structure and function in related brain areas such as MVZ, whether the intervention of CAP can affect the structure and function of the MVZ in sepsis needs to be further verified. Methods64 adults, specific pathogens free Sprague-Dawley male rats were used in this study. The septic models were prepared by cecum ligation and puncture (CLP) method, GTS-21 (a selective α7 nicotinic acetylcholine receptor agonist which can mimic CAP’s activation) and MLA (a powerful and selective nicotine acetylcholine receptor antagonist which can mimic CAP’s blocking) were used to interfere CAP. The pathological changes, apoptosis, the expressions of Tyrosine Hydroxylase (TH) and Choline acetyltransferase (CHAT), the expression levels of GAP-43 mRNA, Olig-2 mRNA, VEGF mRNA, GFAP mRNA, MMP-9 mRNA in MVZ were analyzed among different groups. ResultsIn this study, we found that sepsis induced apoptosis and functional suppression of catecholaminergic and cholinergic neurons and gliosis in MVZ, up-regulated key genes’ expressions such as GAP-43 mRNA，GFAP mRNA，VEGF mRNA，MMP-9 mRNA, down-regulated the expression of Olig-2 mRNA. GTS-21, a selective α7 nicotinic acetylcholine receptor agonist, obviously mitigated the above changes; whereas, methyllycaconitine (MLA), a powerful and selective nicotine acetylcholine receptor antagonist, significantly aggravated these changes. ConclusionsOur research shows that activating CAP can effectively mitigate the neural remodeling and neuronal suppression induced by early sepsis in MVZ, the mechanism may involve with its control of systemic and local inflammation. This study reveals that MVZ and CAP may be potential targets to curb the inflammatory storm in early sepsis.