Dexmedetomidine post-conditioning attenuates cerebral ischemia following asphyxia cardiac arrest through down-regulation of apoptosis and neuroinflammation in rats

Guangqian Li,Pan Gu,Dan Fan,Leiqian Leiqian

doi:10.1186/s12871-021-01394-7

Abstract

BackgroundNeuroprotection strategies after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) remain key areas of basic and clinical research. This study was designed to investigate the neuroprotective effects of dexmedetomidine following resuscitation and potential mechanisms.MethodsAnesthetized rats underwent 6-min asphyxia-based cardiac arrest and resuscitation, after which the experimental group received a single intravenous dose of dexmedetomidine (25 μg/kg). Neurological outcomes and ataxia were assessed after the return of spontaneous circulation. The serum levels and brain expression of inflammation markers was examined, and apoptotic cells were quantified by TUNEL staining.ResultsNeuroprotection was enhanced by dexmedetomidine post-conditioning after the return of spontaneous circulation. This enhancement was characterized by the promotion of neurological function scores and coordination. In addition, dexmedetomidine post-conditioning attenuated the serum levels of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α at 2 h, as well as interleukin IL-1β at 2, 24, and 48 h. TUNEL staining showed that the number of apoptotic cells in the dexmedetomidine post-conditioning group was significantly reduced compared with the control group. Further western blot analysis indicated that dexmedetomidine markedly reduced the levels of caspase-3 and nuclear factor-kappa B (NF-κB) in the brain.ConclusionsDexmedetomidine post-conditioning had a neuroprotective effect against cerebral injury following asphyxia-induced cardiac arrest. The mechanism was associated with the downregulation of apoptosis and neuroinflammation.

Highlights

Neuroprotection strategies after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) remain key areas of basic and clinical research
Recent developments in cardiopulmonary resuscitation (CPR) techniques and postresuscitation care have improved the chances of survival, there are still high rates of death and disability following the restoration of spontaneous circulation (ROSC), mainly due to cerebral injury [3,4,5].Survivors of CA suffer from painful sequelae, including anoxic brain injury, myocardial dysfunction and the systemic ischemia/reperfusion response, which are described as post cardiac arrest syndrome (PCAS)
During the development of PCAS, the systemic ischemia/reperfusion response can trigger a systemic inflammatory cascade, which is the typical pathological process of CA and contributes to the forming of multiple organ dysfunction disease (MODS). This process is similar to the systemic inflammation response syndrome (SIRS), since proinflammatory factors such as Tumor necrosis factor alpha (TNF-α), IL-1βand Nuclear factor-kappa B (NF-κB) can be viewed as injury biomarkers in PCAS [6].The brain consumes the largest amount of oxygen of all organs, and is highly susceptible to disruptions of blood flow

Summary

Introduction

Neuroprotection strategies after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) remain key areas of basic and clinical research. Recent developments in cardiopulmonary resuscitation (CPR) techniques and postresuscitation care have improved the chances of survival, there are still high rates of death and disability following the restoration of spontaneous circulation (ROSC), mainly due to cerebral injury [3,4,5].Survivors of CA suffer from painful sequelae, including anoxic brain injury, myocardial dysfunction and the systemic ischemia/reperfusion response, which are described as post cardiac arrest syndrome (PCAS). During the development of PCAS, the systemic ischemia/reperfusion response can trigger a systemic inflammatory cascade, which is the typical pathological process of CA and contributes to the forming of multiple organ dysfunction disease (MODS) This process is similar to the systemic inflammation response syndrome (SIRS), since proinflammatory factors such as TNF-α, IL-1βand NF-κB can be viewed as injury biomarkers in PCAS [6].The brain consumes the largest amount of oxygen of all organs, and is highly susceptible to disruptions of blood flow. Because of the high incidence of CA and the complex etiology of cerebral ischemia-reperfusion injury, it is urgent to find a therapeutic strategy to attenuate post-CA brain injury

Methods

Results

Discussion

Conclusion