Dexmedetomidine ameliorates acute brain injury induced by myocardial ischemia-reperfusion via upregulating the HIF-1 pathway.

Abstract

Neurological complications after myocardial ischemia/reperfusion (IR) injury remain high and seriously burden patients and their families. Dexmedetomidine (Dex), an α2 agonist, is endowed with analgesic-sedative and anti-inflammatory effects. Therefore, our study aims to explore the mechanism and effect of Dex on brain damage following myocardial IR injury. C57BL/6 mice were randomly divided into Sham, IR, and IR + Dex groups, and myocardial IR models were established. The impact of Dex on brain injury elicited by myocardial IR was assessed via enzyme-linked immunosorbent assay (ELISA) for inflammatory factors in serum and brain; Evans blue for blood-brain barrier (BBB) permeability; Hematoxylin-eosin (H&E) staining for pathological injury in brain; Immunofluorescence for microglia activation in brain; Morris water maze for cognitive dysfunction; Western blot for the expression level of HIF-1α, Occludin, Cleaved caspase-3, NF-κB p65 and p-NF-κB p65 in brain. In addition, HIF-1α knockout mice were used to verify whether the neuroprotective function of Dex is associated with the HIF-1 pathway. Dex was capable of reducing myocardial IR-induced brain damage including inflammatory factor secretion, BBB disruption, neuronal edema, microglial activation, and acute cognitive dysfunction. However, the protective role of Dex was attenuated in HIF-1α knockout mice. Dex protects against myocardial IR-induced brain injury, and the neuroprotection of Dex is at least partially dependent on the activation of the HIF-1 pathway.