Exploring the Mechanism on the Medullary Visceral Zone Inhibiting the Cholinergic Anti-inflammatory Pathway Induced by Sepsis

Inflammatory storm is an important pathological mechanism of multiple organ dysfunction, and it is associated with most deaths in septic patients, deserving to be studied. Recent findings have confirmed that the Medullary Visceral Zone (MVZ) regulates inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP), but how sepsis affects the MVZ and leads to uncontrolled inflammation remain unclear. The current study reported that sepsis induced MVZ to inhibit CAP which underlies the inflammation storm. Our studies have shown that the rat models of sepsis prepared by cecal ligation and puncture had a higher inflammatory level, higher mortality, and higher Murine Sepsis Score. In septic rats, some indicators of heart rate variability (HRV) such as SDNN, HF band, RMSSD, SD1, and SD2 significantly reduced. In MVZ of septic rats, many cholinergic and catecholaminergic neurons showed apoptotic, with low expressions of tyrosine hydroxylase and choline acetyltransferase. The α7nAChR agonist GTS-21 can improve these pathologies, while the α7nAChR antagonist MLA is the opposite. Our study demonstrates for the first time that cholinergic and catecholaminergic neurons in MVZ went through significant apoptosis and inactiveness in sepsis, which contributes to the inhibition of CAP and acceleration of the inflammation storm in early sepsis. Intervening with CAP has a significant effect on the activity and apoptosis of MVZ neurons while altering systemic inflammation and immunity; in addition, for the first time, we confirmed that some indicators of HRV such as SDNN, HF band, RMSSD, SD1, and SD2 can reflect the activity of CAP, but the CAP interference had little effect on these indicators.