COVID-19-Induced Stroke and the Potential of Using Mesenchymal Stem Cells-Derived Extracellular Vesicles in the Regulation of Neuroinflammation.

Ischemic stroke (IS) is a known neurological complication of COVID-19 infection, which is associated with high mortality and disability. Following IS, secondary neuroinflammation that occurs can play both harmful and beneficial roles and lead to further injury or repair of damaged neuronal tissue, respectively. Since inflammation plays a pivotal role in the pathogenesis of COVID-19-induced stroke, targeting neuroinflammation could be an effective strategy for modulating the immune responses following ischemic events. Numerous investigations have indicated that the application of mesenchymal stem cells-derived extracellular vesicles (MSC-EVs) improves functional recovery following stroke, mainly through reducing neuroinflammation as well as promoting neurogenesis and angiogenesis. Therefore, MSC-EVs can be applied for the regulation of SARS-CoV-2-mediated inflammation and the management of COVID-19- related ischemic events. In this study, we have first described the advantages and disadvantages of neuroinflammation in the pathological evolution after IS and summarized the characteristics of neuroinflammation in COVID-19-related stroke. Then, we have discussed the potential benefit of MSC-EVs in the regulation of inflammatory responses after COVID-19-induced ischemic events.

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

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.