Biomol Ther.  2017 Jul;25(4):383-389. 10.4062/biomolther.2015.180.

Neuroprotection of Dexmedetomidine against Cerebral Ischemia-Reperfusion Injury in Rats: Involved in Inhibition of NF-κB and Inflammation Response

• Wang L
• Liu H
• Zhang L
• Wang G
• Zhang M
• Yu Y

• KMID: 2386904
• DOI: http://doi.org/10.4062/biomolther.2015.180

Abstract

Dexmedetomidine is an α2-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of 1 μg/kg load dose, followed by 0.05 μg/kg/min infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-1β, interleukin-6 and tumor nevrosis factor-α as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κBp65, inhibitor of κBα and phosphorylated of κBα in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-κB pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.

Keyword

Cerebral ischemia-reperfusion; Dexmedetomidine; Inflammation; Inducible nitric oxide synthase; Cyclooxygenase-2; Nuclear factor-κB

MeSH Terms

Animals
Brain Edema
CA1 Region, Hippocampal
Cyclooxygenase 2
Cytokines
Dexmedetomidine*
Heart
Hippocampus
Infarction, Middle Cerebral Artery
Inflammation*
Interleukin-6
Kidney
Neuroprotection*
Nitric Oxide Synthase Type II
Rats*
Rats, Sprague-Dawley
Reperfusion
Reperfusion Injury*
RNA, Messenger
Cyclooxygenase 2
Cytokines
Dexmedetomidine
Interleukin-6
Nitric Oxide Synthase Type II
RNA, Messenger