The Neuroprotective Effects of Administration of Methylprednisolone in Cardiopulmonary Resuscitation in Experimental Cardiac Arrest Model Publisher Pubmed



Memary E^{1, 2} ; Imani A³ ; Arhamidolatabadi A^{2, 8} ; Fadavi P^{1, 2} ; Aghajani M³ ; Mohebzadeh F⁴ ; Shahverdishahraki M^{5, 6} ; Dabbagh A^{1, 2} ; Mirkheshti A¹ ; Shirian S^{5, 7} Show Affiliations
Source: Cellular and Molecular Neurobiology Published:2023

Abstract

Although advances in diagnosis and treatment of cardiac arrest (CA) could improve neurological outcomes after cardiopulmonary resuscitation (CPR), survival rate and neurological outcome after CA and CPR remain poor. This study aimed to investigate the effect of epinephrine (EP) alone and EP in combination with methylprednisolone (MP) (EP + MP) on some the apoptotic and anti-apoptotic genes and proteins levels expression of the cerebral cortex as well as neuronal death in a CA rat model. Forty-five male Sprague Dawley rats were randomly divided into three groups including the hypoxic CA + EP, hypoxic CA + EP + MP, and sham groups using a simple randomization procedure. In both hypoxic CA groups, CA was induced by asphyxia and immediately after confirmation of CA, the treatment strategies including chest compression or cardiac massage simultaneously with ventilation, and administration of EP alone (20 mg/kg, every 3 min) and EP (20 mg/kg, every 3 min) + 30 (mg/kg) of MP were done. The sham group only received anesthetic drugs without CA. Some neurological outcomes were investigated using histopathological, immunohistochemical, molecular, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assays at 5 and 48 h post-CPR. The data obtained showed the highest up-regulation of apoptotic genes and proteins expression, the lowest expression of anti-apoptotic gene and protein expression, the most DNA fragmentation and histopathological changes belonged to the EP group on 48 h post-CPR. While mild and intermediate histopathological changes, DNA fragmentation and apoptotic activity was detected in theEP alone and EP + MP groups at 5 h and 48 h post-CPR, respectively. As a novel finding, the present study showed that EP + MP protects neurons from death provoked/induced by hypoxia and reperfusion injury in an experimental model of CA through up and down-regulation of pro- (caspases 3 and 8) and anti-apoptotic (BCL2) molecules, respectively. Graphical Abstract: [Figure not available: see fulltext.] © 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.