Abstract
Xenon has been shown to have neuroprotective effects and is clinically used as a favorable safe inhalation anesthetic. We previously confirmed the neuroprotective effects of xenon treatment in epileptic animals. However, the mechanism underlying these protective effects remains unclear. We aimed to assess the effects of xenon inhalation on autophagy in neuronal injury induced by acute generalized seizures. Kainic acid (KA) was injected into the lateral ventricle of male Sprague–Dawley rats to induce acute generalized seizures. Next, the rats were treated via inhalation of a 70% xenon/21% oxygen/9% nitrogen mixture for 60 min immediately after KA administration. The control group was treated via inhalation of a 79% nitrogen/21% oxygen mixture. Subsequently, two inhibitors (3-methyladenine or bafilomycin A1) or an autophagy inducer (rapamycin) were administered, respectively, before KA and xenon administration to determine the role of autophagy in the protective effects of xenon. The levels of apoptosis, neuronal injury, and autophagy were determined in all the rats. Xenon inhalation significantly attenuated the severity of the seizure-induced neuronal injury. Increased autophagy accompanied this inhibitive effect. Autophagy inhibition eliminated these xenon neuroprotective effects. A simulation of autophagy using rapamycin recapitulated xenon’s protective effects on KA-induced acute generalized seizures in the rats. These findings confirmed that xenon exerts strong neuroprotective effects in KA-induced acute generalized seizures. Further, they indicate that increased autophagy may underlie the protective effects of xenon. Therefore, xenon and autophagy inducers may be useful clinical options for their neuroprotective effects in epileptic seizures.
Highlights
Epilepsy is a common neurological disease that affects 0.5–1% of the worldwide population with potentially serious consequences, including neuronal injury and cognitive defects
We found that xenon treatment significantly attenuated kainic acid (KA)-induced changes in apoptosis-related proteins
Consistent with this, xenon treatment significantly attenuated the increased number of positive Fluoro-Jade B (FJB) signals in the CA3 and pyriform cortex (PC) after KA administration (n = 5 per group, Figures 1G,H). These findings indicate that xenon inhalation could prevent apoptosis and neuronal injury associated with KA-induced acute generalized seizures
Summary
Epilepsy is a common neurological disease that affects 0.5–1% of the worldwide population with potentially serious consequences, including neuronal injury and cognitive defects. There are currently available drug and surgical treatment options for epilepsy and associated cognitive defects They have several limitations, including drug resistance, serious side effects, and recrudescence (Schmidt and Löscher, 2005; Chen et al, 2018). Xenon is clinically used as a safe anesthetic agent and is popular due to having almost no side effects. It has been recently receiving increased attention due to its superior neuroprotective effects, which have been confirmed in Alzheimer’s disease (Lavaur et al, 2016a,b) and in ischemia/reperfusion injury (Cattano et al, 2011; Yang T. et al, 2012; Yang et al, 2014; Metaxa et al, 2014). Further studies are required to explore the underlying mechanisms of xenon treatment effects and reveal potential targets for neuronal protection in epilepsy and seizure
Sign-in/Register to view highlights & summary 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.
