Original articleHypothermia induced by anesthesia regulates various signals expressions in the hippocampus of animals
Introduction
General anesthesia plays an important role in various medical procedures. However, it is not free of problems. General anesthesia is reported to induce learning deficits and influence memory [1], [2]. In addition, it induces pernicious effects on the neurogenesis of hippocampus [3]. General anesthesia causes severe complications, known as molecular events in central nervous system (CNS). Additionally, general anesthesia leads to the alterations of numerous genes expression in different regions of brain [4]. Nevertheless, it is still not fully understood of anesthesia-caused molecular changes.
Various studies reported that hypothermia could result in memory disruption in various organisms including rodents [5]. For instance, cooling leads to memory loss in rats [6]. Several studies indicated that protein synthesis, transcriptions or translation are involved in hypothermia-induced memory disruption [7], [8]. However, the molecular mechanism about how hypothermia induces memory dysfunction is not understood fully. And hypothermia is a common complication of anesthesia, which could result in negative outcomes. Anesthetic agents affect hypothermia through reducing the hypothalamic thermoregulatory set point for shivering and through increasing the core-to-peripheral heat redistribution by vasodilation, which is a main cause of hypothermia in the short surgical protocols [9], [10]. Isoflurane is a commonly used inhalant anesthetic. The advantages of inhalant agents involve their low blood gas solubility, resulting in both rapid induction of and recovery from anesthesia, minimal hepatic metabolism, and precise control of anesthetic depth [11], [12]. Isoflurane has been reported to reduce adenosine triphosphate (ATP) levels in vitro, which might be associated with hypothermia, as well as the complications induced by hypothermia to organisms [13].
Here in our study, we found that in vivo, during isoflurane anesthesia treatment for short time under hypothermic conditions, FGF2 and Arc were down-regulated, GFAP, Iba1 and p-eEF2 were up-regulated, and p-p38, p-ERK1/2 and p-JNK were all decreased. And in vitro, hypothermic incubation of cells further proved our supposing that hypothermia might be a direct factor, leading to the reduction of FGF2 and Arc, augment of GFAP, Iba1 and p-eEF2, as well as the decreasing of MAPKs family members. Together, our study supplied new molecular insights into the regulation of a variety of signals by anesthesia-induced hypothermia.
Section snippets
Animals and treatment
14-16-week-old male Fisher 344 rats were obtained from the Ninth People’s Hospital Animal Center (Shanghai, China). And 12-week-old C57BL/6J mice were purchased from Animal Experiment Center of Nanjing Medical University (Nanjing, China). Before the experiments, all rats were required to adapt to the environment for a week. All procedures were carried out in line with the Regulations of Experimental Animal Administration issued by the Ministry of Science and Technology of the People’s Republic
The effect of isoflurane anesthesia on cellular stress-related genes expression
Isoflurane is widely used for inhalational anesthesia both in humans and animals [15]. Rats were treated with 1 minimum alveolar concentration isoflurane, which is a clinically relevant concentration allowing spontaneous ventilation. And the hemodynamic parameters in rodents are not influenced in the absence or presence of temperature maintaining [16]. In the end of the isoflurane treatment, significant hypothermia was observed without warming devices (29.2 ± 1.3 °C). Here, we analyzed different
Discussion
Inhalation of anesthetic isoflurane has been suggested to trigger the neurotoxicity related to neuropathogenesis and damage [24]. According to studies before, hypothermia has been classified into the mild (34.5–36.5 °C), the moderate (34.5–32 °C), the marked (28–32 °C), and the profound hypothermia (<28 °C) [25]. Mild hypothermia is reported as a neuroprotective strategy, which might be effective to treat brain injuries [26]. Hypothermia could reduce the metabolic rate, which is then likely to
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Auricular transcutaneous vagus nerve stimulation improves memory persistence in naïve mice and in an intellectual disability mouse model
2020, Brain StimulationCitation Excerpt :In agreement, previous studies have revealed the modulation of memory function using invasive and non-invasive approaches of VNS in animal models and in humans [16–18], but, to the best of our knowledge non-invasive transcutaneous approaches had not been assessed in mouse models. We run atVNS under normothermic conditions and using a low dose of isoflurane to prevent alterations in hippocampal signaling pathways relevant for cognition [19,20]. Our anesthesia conditions revealed no alteration of memory performance compared to non-anesthetized mice, ruling out this step as a potential bias in our behavioral results.