Neuroprotective Effects of Pretreatment with Propofol in LPS-Induced BV-2 Microglia Cells: Role of TLR4 and GSK-3β

Abstract

Surgery often leads to neuroinflammation, which mainly acts as the activation of microglia cells. Propofol is always used for induction and maintenance of anesthesia prior to surgical trauma, whereas whether or not it could attenuate neuroinflammation used prophylactically is not well defined. In the present study, we incubated BV-2 microglia cells with 1 μg/ml lipopolysaccharide (LPS) to mimic neuroinflammation in vitro. Firstly, cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and the data indicated that propofol would not reduce cell viability unless its concentration reached 300 μM. Secondly, BV-2 microglia cells were pretreated with 30 μM propofol (clinically relevant concentration), and then stimulated with LPS. The results showed that the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-10 was considerably increased by LPS, but the change could be markedly attenuated by pretreatment with propofol. Meanwhile, pretreatment with propofol inhibited LPS-induced augmentation of toll-like receptor 4 (TLR4) expression at both mRNA and protein levels and further upregulated LPS-induced inactivation of glycogen synthase kinase-3β (GSK-3β) in BV-2 microglia cells. These results indicated, at least in part, that pretreatment with propofol can protect BV-2 microglia cells against LPS-induced inflammation. Downregulation of TLR4 expression and inactivation of GSK-3β may be involved in its protective effect.

Propofol Protects Against Focal Cerebral Ischemia via Inhibition of Microglia-Mediated Proinflammatory Cytokines in a Rat Model of Experimental Stroke

“…These findings provided evidence for suppressive effects of propofol on microglial activation and release of proinflammatory cytokines in vivo in rats after ischemic stroke. Our current data are supported by recent in vitro studies showing that propofol dramatically reduced levels of proinflammatory cytokines TNF-α, IL-1β and IL-6, and activation of microglia induced by lipopolysaccharide [11,38] or extracellular pressure [39]. Taken together, these observations demonstrate that the beneficial effects of propofol on infarct volume and neurological outcome are associated with inhibition of microglia activation and suppression of the exaggerated production of proinflammatory cytokines in ischemic brain early after ischemic stroke.…”

Protective Effects of Pretreatment with Oleanolic Acid in Rats in the Acute Phase of Hepatic Ischemia-Reperfusion Injury: Role of the PI3K/Akt Pathway

“…Glycogen synthase kinase (GSK-3 β ) activity has recently been identified in a number of studies as crucial in the regulation of the inflammatory response [11, 12]. Its inactivation is also involved in indirubin-3′-oxime-induced protection against hepatic IR injury in rats [13].…”

Pyrrolidine dithiocarbamate attenuates surgery-induced neuroinflammation and cognitive dysfunction possibly via inhibition of nuclear factor κB

“…These results suggest that propofol-based general anesthesia at surgical anesthesia level for 2 h did not cause cognitive impairment and neuroinflammation. Interestingly, propofol has been shown to reduce lipopolysaccharide-induced proinflammatory cytokine production in microglial and macrophage cultures (Wu et al, 2009; Gui et al, 2012). It is not known whether propofol anesthesia has partly inhibited surgery-induced neuroinflammation in our study.…”