Hypothalamic CRH Neurons Modulate Sevoflurane Anesthesia and The Post-anesthesia Stress Responses

Kavli Affiliate: Wei Min

| Authors: Shan Jiang, Lu Chen, Wei-Min Qu, Zhi-Li Huang and Chang-Rui Chen

| Summary:

General anesthesia is a fundamental process required to undertake safely and humanely a high fraction of surgeries and invasive diagnostic procedures. However, the undesired stress response associated with general anesthesia (GA) causes delayed recovery and even increased morbidity in the clinic. Here, a core hypothalamic ensemble, corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (PVHCRH neurons) is discovered, which regulates the anesthetic effects and post-anesthesia stress response of sevoflurane GA. Chemogenetic activation of these neurons delay the induction of and accelerated emergence from sevoflurane GA, whereas chemogenetic inhibition of PVHCRH neurons accelerates induction and delays awakening. Moreover, optogenetic stimulation of PVHCRH neurons induce rapid cortical activation during both the steady and deep sevoflurane GA state with burst-suppression oscillations. Interestingly, chemogenetic inhibition of PVHCRH neurons relieve the sevoflurane GA-elicited stress response (e.g., excessive self-grooming and elevated corticosterone level). These findings identify PVHCRH neurons modulate states of anesthesia in sevoflurane GA, being a part of anesthesia regulatory network of sevoflurane.

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