Dexmedetomidine confers neuroprotection against transient global cerebral ischemia/reperfusion injury in rats: Anti-inflammatory effect through inactivation of the TLR-4/NF-κB pathway

Abstract

Group C underwent transient global ischemia(10 min)

Group D received DXM 30 min before ischemia

Group R received resatorvid, a selective TLR-4 antagonist, 30 min before ischemia

and Group RD received resatorvid and DXM 30 min before ischemia. The numbers of necrotic and apoptotic cells and the levels of TLR-4, NF-κB, and caspase-3 were assessed 1 day after ischemia, and pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin 6 (IL-6) were measured before ischemia and 2,6, and 24 h thereafter. Results:The necrotic and apoptotic cell counts and levels of TLR-4, NF-κB, and caspase-3 were higher in Group C than in other groups. TNF-α were higher in Group C than in other groups 2 h afterischemia,whereas IL-6 were higher in Group C 6 h after ischemia. IL-1βwas higher in Group C than in Group D 6 and 24 h after ischemia. Conclusions: Our findings suggest that the anti-inflammatory action of DXM via inactivation of the TLR-4/NF-κB pathway, in part, may explain DXM-induced neuroprotection after cerebral ischemia.

Objective: Dexmedetomidine (DXM) has anti-inflammatory effects, which is considered an important mechanism of DXM-induced neuroprotectionfrom cerebral ischemia/reperfusion injury. We determined whetherthe anti-inflammatory effects of DXM are associated with inhibition of the toll-like receptor (TLR)-4/nuclear factor kappa B (NF-κB) pathway in a rat model of transient global cerebral ischemia/reperfusion injury. Methods: Fifty rats were randomly assigned to one of five groups (10 rats/group): Group S received no treatment