Protective role of isoflurane pretreatment in rats with focal cerebral ischemia and the underlying molecular mechanism

Abstract

Abstract. Inflammation and immunity are important in the pathogenesis of cerebral ischemia. Toll-like receptor 4 (TLR4) is involved in the inflammatory responses of injured brain tissues. Emerging studies have focused on the effect of isoflurane (ISO) pretreatment on cerebral ischemia, however, the association between ISO pretreatment and TLR4 during cerebral ischemia remains to be elucidated. In the present study, the protective role of ISO pretreatment in rats with focal cerebral ischemia reperfusion was investigated and the molecular mechanism was discussed. Using a middle cerebral artery occlusion (MCAO) model, triphenyltetrazolium chloride staining was utilized to measure the infarct volume and brain edema and immunofluorescence staining was used to detect the MCAO-induced TLR4 expression and localization. Western blot analyses were conducted to quantify the protein expression levels of TLR4, myeloid differentiation primary response 88 (MyD88) and nuclear factor (NF)-κB in ischemic brain tissue at different time points. The results demonstrated that, following ISO pretreatment, the neurological deficits, brain edema and cerebral infarct size caused by ischemia/reperfusion were attenuated. The astrocyte and microglial activation in the brain tissue was decreased. In addition, the expression levels of TLR4, MyD88 and NF-κB were decreased. The present study indicated that ISO pretreatment may protect the brain from ischemic damage by downregulating the expression levels of TLR4, MyD88 and NF-κB.

Lack of Specific Involvement of (+)-Naloxone and (+)-Naltrexone on the Reinforcing and Neurochemical Effects of Cocaine and Opioids

“…Both ketamine and isoflurane have been reported to impact neuro-inflammation, with acute and long-lasting effects (Lockwood et al, 1993;Miyazaki et al, 1997;Wu et al, 2008;Xiang et al, 2014;Xiao et al, 2015;Zhao et al, 2011). Further, changes in glutamate, GABA, and calcium ++ oscillation signaling have been reported after isoflurane anesthesia (Miyazaki et al, 1997;Xiang et al, 2014;Zhao et al, 2011).…”

Isoflurane preconditioning inhibits the effects of tissue-type plasminogen activator on brain endothelial cell in an in vitro model of ischemic stroke

“…Moreover, isoflurane may transiently hamper the progression and delay the onset of cerebral infarct 26. In addition, isoflurane pretreatment reduces neurological deficits, brain edema, and cerebral infarct size after ischemia/reperfusion 11. We determined in the previous study that isoflurane post-treatment has a protective effect on tPA-exaggerated brain injury 1; however, the protective mechanisms of isoflurane against tPA-induced injury after ischemic insult were not elucidated.…”

“…Many experimental studies have demonstrated that isoflurane provides protective effects in many organs after ischemic reperfusion injury 8-10. Isoflurane pretreatment reduced neurological deficits, brain edema, and infarction volume in ischemic animal model 11. Furthermore, isoflurane preconditioning attenuates inflammation and injury by decreasing pro-apoptotic factors and increasing anti-apoptotic factors 12.…”

Isoflurane preconditioning provides neuroprotection against stroke by regulating the expression of the TLR4 signalling pathway to alleviate microglial activation

“…In particular, Toll-like receptor 4 (TLR4) is expressed primarily in microglia151617. We and other studies have reported that TLR4 can induce microglial activation and cytokine production in brain injury, trauma and neurodegenerative diseases1819. Moreover, Hara et al reported that TLR4 knockout (KO) mice had significantly smaller infarct volumes and better neurobehavioural recovery at 24 h after I/R injury compared with wild-type mice.…”