Microglial activation-induced
neuroinflammation is closely related to the development of
sepsis-associated encephalopathy. Accumulating evidence suggests that changes in the metabolic profile of microglia is crucial for their response to
inflammation.
Propofol is widely used for sedation in mechanically ventilated patients with
sepsis. Here, we investigate the effect of
propofol on
lipopolysaccharide-induced
neuroinflammation, neuronal
injuries, microglia metabolic reprogramming as well as the underlying molecular mechanisms. The
neuroprotective effects of
propofol (80 mg/kg) in vivo were measured in the
lipopolysaccharide (2 mg/kg)-induced
sepsis in mice through behavioral tests, Western blot analysis and immunofluorescent staining. The anti-inflammatory effects of
propofol (50 μM) in microglial cell cultures under
lipopolysaccharide (10 ng/ml) challenge were examined with Seahorse XF Glycolysis Stress test, ROS assay, Western blot, and immunofluorescent staining. We showed that
propofol treatment reduced microglia activation and
neuroinflammation, inhibited neuronal apoptosis and improved
lipopolysaccharide-induced
cognitive dysfunction.
Propofol also attenuated
lipopolysaccharide-stimulated increases of
inducible nitric oxide synthase,
nitric oxide,
tumor necrosis factor-α, interlukin-1β and COX-2 in cultured BV-2 cells.
Propofol-treated microglia showed a remarkable suppression of
lipopolysaccharide-induced HIF-1α, PFKFB3, HK2 expression and along with downregulation of the ROS/PI3K/Akt/mTOR signaling pathway. Moreover,
propofol attenuated the enhancement of mitochondrial respiration and glycolysis induced by
lipopolysaccharide. Together, our data suggest that
propofol attenuated inflammatory response by inhibiting metabolic reprogramming, at least in part, through downregulation of the ROS/PI3K/Akt/mTOR/HIF-1α signaling pathway.