Abstract
Background17AAG has been extensively studied for its antitumor effects that protect cells from lethal stress by maintaining protein stability. The role of 17AAG in sevoflurane-induced neuronal injury has never been studied. We aim to investigate the effect of 17AAG on sevoflurane-induced neurotoxicity in vivo and in vitro.MethodsSevoflurane-induced hippocampal neuron injury model was established in aged Sprague–Dawley rats. Pretreatment of vehicle or 17AAG was administered prior to sevoflurane inhalation. H4 neuroglioma cells were pretreated with vehicle or 17AAG and exposed to sevoflurane. Apoptosis, oxidative stress, expression of interleukin-6 (IL-6), and activation of the nuclear factor-κB (NF-κB) signaling pathway in H4 cells were examined by Hoechst assay, flow cytometry, Western blot, and immunofluorescent staining. RNA interference against HSPA1A was performed to test the function of HSP70 in neuroprotection.ResultsExogenous 17AAG reduced sevoflurane-induced apoptosis and oxidative stress in rat hippocampal neurons and in H4 cells. In H4 cells, 17AAG suppressed sevoflurane-induced upregulation of IL-6 and activation of NF-κB signaling. 17AAG enhanced sevoflurane-induced upregulation of HSP70 in rat hippocampal neurons and in H4 cells. Conversely, silencing of HSPA1A in H4 cells blocked the cytoprotective effect of 17AAG against sevoflurane-induced apoptosis and oxidative stress, and prevented upregulation of IL-6 and activation of NF-κB signaling.Conclusions17AAG protects against sevoflurane-induced neurotoxicity in vivo and in vitro via HSP70-dependent inhibition of apoptosis, oxidative stress, and pro-inflammatory signaling pathway.
Highlights
17AAG has been extensively studied for its antitumor effects that protect cells from lethal stress by maintaining protein stability
Pretreatment with 17AAG further enhanced the HSP70 induction by nearly two folds (Fig. 4). These results suggest that upregulation of HSP70 may play a critical role in the neuroprotection by 17AAG. 17AAG further upregulated the expression of HSP70, which was initially induced by sevoflurane
HSP70 was required for the cytoprotective effect of 17AAG against sevoflurane‐induced neuronal injury Given the involvement of HSP70 in neuroprotection against sevoflurane injury in vivo and in vitro (Fig. 4), we further investigated the role of HSP70. Small interfering RNA (siRNA) designed against HSPA1A could knock-down HSP70 expression in H4 cells (Fig. 5a–c)
Summary
The role of 17AAG in sevoflurane-induced neuronal injury has never been studied. We aim to investigate the effect of 17AAG on sevoflurane-induced neurotoxicity in vivo and in vitro. Volatile inhalation anesthetics are the most commonly used agents to induce and maintain general anesthesia. Sevoflurane is currently the most commonly used inhalation anesthetic agent in developed nations. Favored for its rapid onset and minimal airway disturbance, sevoflurane has been implicated in emergence delirium [8] and other neurotoxic effects such as anesthesia-induced developmental neurotoxicity (AIDN) [21, 35]. Given that there is no cure or specific treatment for anesthetic neurotoxicity, identifying novel strategy to prevent and treat sevoflurane-induced neuronal injury is a public health need
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
