Propofol ameliorates ischemic brain injury by blocking TLR4 pathway in mice

Ischemic brain injury is one of the most serious perioperative complications. However, effective preventative methods have not yet been established. This study aimed to investigate whether propofol has neuroprotective effects against ischemic brain injury, with a specific focus on Toll-like receptor 4 (TLR4). Focal brain ischemia was induced via a combination of left common carotid artery occlusion and distal left middle cerebral artery coagulation in mice. Either propofol (10 mg/kg) or vehicle was intravenously injected 10 min prior to the induction of brain ischemia in wild-type and TLR4 knockout mice. Infarct volume, pro-inflammatory cytokine expression, inflammatory cell infiltration, and neurobehavioral function were assessed. Propofol administration significantly reduced infarct volume in wild-type mice (26.9 +/- 2.7 vs 15.7 +/- 2.0 mm(3) at day 7), but not in TLR4 knockout mice. Compared with the control mice, the propofol-treated wild-type mice exhibited lower levels of IL-6 (0.57 +/- 0.23 vs 1.00 +/- 0.39 at 24 h), and smaller numbers of TLR4-expressing microglia in the penumbra (11.7 +/- 3.1 vs 25.1 +/- 4.7 cells/0.1 mm(2)). In conclusion, propofol administration prior to ischemic brain insult attenuated brain injury by blocking the TLR4-dependent pathway and suppressing pro-inflammatory cytokine production.