Abstract
Previous studies have reported the possible neuroprotective effects of xenon treatment. The purpose of this study was to define the range of effective xenon ratio, most effective xenon ratio, and time-window for intervention in the kainic acid (KA) – induced status epilepticus (SE) rat model. Different ratios of xenon (35% xenon, 21% oxygen, 44% nitrogen, 50% xenon, 21% oxygen, 29% nitrogen, 70% xenon, 21% oxygen, and 9% nitrogen) were used to treat the KA-induced SE. Our results confirmed the anti-seizure role of 50 and 70% xenon mixture, with a stronger effect from the latter. Further, 70% xenon mixture was dispensed at three time points (0 min, 15 min delayed, and 30 min delayed) after KA administration, and the results indicated the anti-seizure effect at all treated time points. The results also established that the neuronal injury in the hippocampus and entorhinal cortex (EC), assessed using Fluoro-Jade B (FJB) staining, were reversed by the xenon inhalation, and within 30 min after KA administration. Our study, therefore, indicates the appropriate effective xenon ratio and time-window for intervention that can depress seizures. The prevention of neuronal injury and further reversal of the loss of effective control of depress network in the hippocampus and EC may be the mechanisms underlying the anti-seizure effect of xenon.
Highlights
Available anti-epileptic interventions such as anti-epileptic drugs, resection, and deep brain stimulation have a limited efficacy (Wang et al, 2015; Falcicchia et al, 2018; Kaur et al, 2019)
The rats in 50 or 70% xenon inhalation groups showed significantly attenuated seizure stage from the second 5 min onward as compared with the control group treated with 21% oxygen, 79% nitrogen (P = 0.006 and P < 0.001, respectively, Figure 1A)
The results showed that the cumulative generalized seizures duration was significantly reduced after 50 or 70% xenon treatment (KA, 53.3 min; 50% xenon, 34.6 min; 70% xenon, 3.4 min; P < 0.001 and 0.001, Figure 1B)
Summary
Available anti-epileptic interventions such as anti-epileptic drugs, resection, and deep brain stimulation have a limited efficacy (Wang et al, 2015; Falcicchia et al, 2018; Kaur et al, 2019). Most patients with epilepsy depend on anti-epileptic drugs to control seizures. These possess a few drawbacks such as drug resistance that influence about one-third of the individuals (Schmidt and Löscher, 2005). The surgical treatment of epilepsy is not suitable for all refractory epilepsy cases (Wiebe et al, 2001; McIntosh et al, 2004). As the recently established epileptic therapy, deep brain stimulation could control a part of refractory epilepsy cases; it has a few drawbacks such as selection of stimulation region and parameters for different types of epilepsy (Cohen-Gadol et al, 2003; Theodore and Fisher, 2004) and some other complications (Lesser, 2000; Smyth et al, 2003). It is important to develop therapies that can depress seizures and reduce the epileptic brain injury
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