Effects of sevoflurane on rats with ischemic brain injury and the role of the TREK-1 channel

Abstract

The purpose of this investigation was to determine the effects of sevoflurane on rats with ischemic brain injury and to determine the potential role of the TREK-1 channel in this process. Normal rats were randomly divided into three groups: Sham operation, sevoflurane anesthesia or chloral hydrate anesthesia group, an additional group of TREK-1 knockout rats were also studied. Semi-quantitative PCR and western blot analysis confirmed the lack of TREK-1 expression in the brain of TREK-1 knockout rats. The thread-tie method was used to establish middle cerebral artery occlusion (MCAO) model to induce cerebral ischemic brain injury. All rates were treated for 4 days prior to ischemia (for 2 h) followed by a 24 h reperfusion period. Physiological indexes of rats in each group both prior to and after surgery showed no statistical difference (P>0.05). Neurological function was scored both before (no statistical difference) and after surgery where it was found to be significantly better (lower score) in the sevoflurane anesthesia group than in chloral hydrate anesthesia and TREK-1 knockout groups (P<0.01). The area of cerebral infarction was measured by triphenyl tetrazolium chloride staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to detect the apoptosis of brain cells. TTC staining showed different degrees of cerebral infarction in the various groups; the area of cerebral infarction in sevoflurane anesthesia group was significantly lower than that in chloral hydrate anesthesia and TREK-1 knockout groups (P<0.01). TUNEL assay showed that the number of TUNEL-positive cells was significantly lower in sevoflurane anesthesia group than in TREK-1 knockout and chloral hydrate anesthesia groups (P<0.01). In conclusion, results from this investigation showed that sevoflurane can protect the nerve function of rats with cerebral ischemic brain injury possibly by affecting the expression of proteins involved in the TREK-1 signaling pathway.

A study of optimal concentration range and time window of sevoflurane preconditioning for brain protection in MCAO rats

“…There are several mechanisms of brain protection for sevoflurane preconditioning, such as by inhibition of oxygen free radicals [11], anti-inflammation [15], activation of antioxidant enzymes [11], reduction of expression of apoptosis-related proteins [16], regulation of TREK-1 [9] and TREK-2 channel [8], inhibition of thioredoxin [17], etc. However, this study is limited as it considered only the concentration and time window of sevoflurane preconditioning, but the specific mechanism is not studied, which is also our future research direction.…”

“…However, due to very narrow time window for anticoagulant therapy, many patients miss the best time for effective treatment. Therefore, several recent studies have focused on neuroprotection strategies of stroke [8,9]. These therapeutic approaches have important clinical and social significances in effectively studying the prevention and treatment measures of perioperative stroke.…”

“…Preconditioning is an important biological phenomenon that often occurs under non-lethal conditions, such as high temperatures, exercise, systemic or ischemia, inflammation or general anesthesia [9,10]. This is defined as delivering a stimulus below the threshold for tissues or organs to develop tolerance to induce subsequent stimuli above the threshold.…”

18F‑fluorodeoxyglucose positron emission tomography for the detection of inflammatory lesions of the arterial vessel walls in Wistar rats

“…After micro-PET imaging, rats were intraperitoneally injected with chloral hydrate (400 mg/kg) for anesthesia ( 14 , 15 ), and euthanized by cardiac perfusion with normal saline and 4% paraformaldehyde. Death was confirmed by cardiac and respiratory arrest.…”

Role of TREK-1 in Health and Disease, Focus on the Central Nervous System

“…Recently, in vitro and in vivo preconditioning with sevoflurane was shown to provide neuroprotection through activation of TREK-1 channels (Tong et al, 2014). Rats treated with the anesthetic sevoflurane after MCAO display neuroprotection which seems to be mediated by TREK-1 channels (Table 3; Pan et al, 2017).…”