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

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.

Retracted: Protective effects of Progranulin against focal cerebral ischemia‐reperfusion injury in rats by suppressing endoplasmic reticulum stress and NF‐κB activation in reactive astrocytes

“…After ischemia, blood reperfusion involved in the ischemic region leads to more severe damage and malfunctions in the tissues and is a major cause of cerebral ischemiareperfusion (I/R) injury. 1 Reperfusion may reduce infarction volume while improving patients' conditions initially, however reperfusion occurring after a long period of ischemia is likely to be the cause of a higher infarction volume and in turn aggravate the initial injury. 2 The Qing Shu, Hua Fan, and Shi-Jun Li authors contributed equally.…”

Dexmedetomidine protects mice against myocardium ischaemic/reperfusion injury by activating an AMPK/PI3K/Akt/eNOS pathway

“…Renal IRI up‐regulated the expression of TNF‐α, IL‐1β, ICAM‐1, HMGB1 and TLR4, which were alleviated by the treatment with Dex . It was also reported that Dex reduced focal cerebral ischaemia‐reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators as well as oxidative products . In an animal model of spinal cord ischaemia‐reperfusion injury, the numbers of proinflammation cytokines of the Dex group were decreased, whereas anti‐inflammation cytokines increased .…”

The Role of Noncoding RNAs in Brain Cells during Rat Cerebral Ischemia

“…An increase of the mRNA level of the gene for INOS, encoding an enzyme for the synthesis of NO, also participating in the development of the inflammatory response in the lesion, was also noted [22,25]. In the ischemia-reperfusion model, it was also shown that cytokines (IL-1β, IL6), adhesion molecules (ICAM1, E-selectin, MMP-9), MAPK kinase, and c-fos transcription factors were involved in the development of inflammation [17,20,23,[26][27][28][29]. Wang et al studied the molecular mechanism of ischemia-reperfusion pathogenesis using genome-wide transcriptome analysis (RNA-Seq) in the hippocampus of rats at 24 h after tMCAO.…”

“…In particular, activation of the transcription factor Nf-κb was shown. An increase of the mRNA level of Cox2, which encodes one of the key enzymes for the synthesis of the pro-inflammatory prostaglandin E2 (PGE2), was accompanied by an increase in the level of the corresponding protein, not only at the source but also in adjacent regions, and accompanied by increased concentration of PGE2 [20][21][22]. At the same time, as a result of the opening of the blood-brain barrier in brain sections, extensive leucocyte infiltration was observed [21,23,24].…”