Cardiac Arrest (CA) in infants and children is secondary to asphyxia in a majority of cases.
The Mioara Manole Laboratory has developed an animal model in immature rats that mimics pediatric asphyxial CA. In this model the lab has identified pathologic alterations of CBF post-resuscitation that are region- and insult duration-dependent: (i) cortical hypoperfusion after insults of moderate duration (in-hospital CA model), (ii) generalized hypoperfusion after insults of prolonged duration (out-of-hospital CA model). The lab has reported that CBF-directed therapies improved neurological outcome in our model. Thus, CBF dysregulation after pediatric asphyxial CA is an important target for novel therapies.
The lab's long-term research goal is to elucidate key vascular pathways involved in pathologic cerebral blood flow (CBF) dysregulation after pediatric asphyxial CA and to develop therapeutic strategies that prevent CBF dysregulation and secondary neuronal damage. Essential in maintaining neuronal function during this critical period of secondary insults are metabolites that alter both CBF and neuronal survival, such as eicosanoid metabolites of arachidonic acid. The goal of the current projects is to elucidate mechanisms through which eicosanoid metabolites of cytochrome (CYP) 4A/4F and 2C/2J produce CBF dysregulation and neurotoxicity after pediatric CA and to develop innovative therapies that target these pathways.