Vagus Nerve And DVC Is Required For Cholinergic Antiinflammatory Pathway Control Of TNF In Endotoxemia

Some dataes have indicated that Acetylcholine (ACh), the principal neurotransm -itter of the vagus nerves, is a key mediator of the cholinergic anti-inflammatory pathway. Huang Jian have used a method of crushing the vagus nerve to record the frequency of cervical vagal efferent discharge and found the vagal efferent discharge significantly increased after LPS injection. Saddam studies revealed that surgical dissection of the efferent vagus nerve enhanced the production of proinflammatory cytokines and accelerated the development of septic shock. In addition, studies have revealed that electrical stimulation of efferent vagal nerve fibres inhibits inflammation and reduced lethality by suppressing the release of pro-inflammatory cytokines (Boro- vikova, Thomas, Shi Deguang and Hu Sen). The methods of crushing, electrical stimulation and vagotomy were used in the previous studies on the vagus nerves role in regulating inflammation. However, There is no study on the role of the intact vagus efferent nerve in systemic inflammatory response in endotoxemia rats.The vagus efferent nerve and neurotransmitter Ach involved in the anti-inflam- matory response, and this results showed that inflammatory response have activated vagus preganglionic neurons in the DMV. Howerver, how was the inflammatory information relayed to the DMV? the immune information can signal the brain through two pathways:The first, cytokines of the bloodstream passed through the lack of blood-brain barrier of the AP into the brain, then directly transmit to the DMV or indirectly transmit to the DMV by the NTS; The second, cytokine release in the periphery is sensed by receptors located on the vagus nerve. This information is transmitted to the NTS in the brain stem and subsequently to the DMN. It remains unclear whether inflammatory information was transmitted to the brain stem mainly through the lack of blood-brain barrier of the AP or vagus afferent nerve, or both in cholinergic anti-inflammatory pathway.The medulla oblongata internal organs belt contains many different types of active materials such as the catecholamines. A series of research indicated that CA neurons within the MVZ participated in the regulation of the cardiovascular and gastrointestinal function. Fos expression of CA neurons in the MVZ significantly increased during the acute stage of cerebral hemorrhage. The Fos/TH expression in DVC increased under water immersion and restraint stress however, whether CA neurons in NTS, DMV and AP participate in the transmission, analysis and conformity of inflammatory information has not been reported Therefore, This present study was designed to examine the discharge of vagal efferent fibers, levels of TNF-αin the serum and c-Fos/TH expression of DVC in endotoxin-induced inflammation to further explore the function and the mechanism of vagus nerve and DVC in the cholinergic anti-inflammatory pathway.This study was divided into three parts:The first part recorded the vagus nerve discharge, blood pressure, levels of TNF-αin the serum and the c-fos expression of DVC after LPS injection. The experiment was divided into two groups: the LPS group treated with LPS and the CON group treated with saline. Results and conclusions: discharge frequency of the vagal nerve was significantly increased after LPS injected, but there was no significant different on blood pressure before or after LPS injection;compared with the control group, discharge frequency of the vagal nerve, levels of serum TNF-αand c-Fos expression in the NTS, DMV and AP were significantly increased after LPS injected. This experiment showed the vagus nerve, AP and NTS participated in Inflammation.The second part recorded the vagus nerve discharge, blood pressure, level of serum TNF-αand c-fos expression of DVC in LPS-induced inflammation after capsaicin denervation. The experiment was divided into two groups: the CAS group which LPS was intravenous injected after denervation with capsaicin and the LPS group which LPS was intravenous injected. Results and conclusions: discharge frequency of vagal efferent fibers in CAS was significantly increased after LPS injected in CAS group, but not blood pressure; compared with the LPS group, the serum TNF-αlevel was obviously increased in CAS, but c-fos expression in DVC was significantly reduced. The results revealed that the excitability of vagus efferent nerve fibers increased during the endotoxin inflammation, so that the efferent vagus nerve fibers involved in anti-inflammatory response. Peripheral inflammatory information is mainly passed through the vagus afferent nerve to NTS, then transmit to the DMV, and some inflammatory signals can be transmitted through the AP to DMV.The third part, the method of double-target immunological of Fos protein and tyrosine hydroxylase (TH) was used to research the CA neurons activities in the brain stem NTS,DVC and AP during the endotoxin inflammation. The experiment was divided into two groups: the LPS group treated with LPS and the CON group treated with saline.Results and conclusions: compared with the CON group, the majority of the Fos protein activated neuron were CA neuron during the endotoxin inflammation.The results indicated that CA neuron which consisted in NTS,DMV and AP in brainstem involved in the inflammation information of the transfer, analysis and integration in the cholinergic anti-inflammatory pathway during the endotoxin inflammation.