losartan-potassium and 2-iminobiotin

Perinatal asphyxia is characterized by oxygen deprivation and lack of perfusion in the perinatal period, leading to hypoxic-ischemic encephalopathy and sequelae such as cerebral palsy, mental retardation, cerebral visual impairment, epilepsy and learning disabilities. On cellular level PA is associated with a decrease in oxygen and glucose leading to ATP depletion and a compromised mitochondrial function. Upon reoxygenation and reperfusion, the renewed availability of oxygen gives rise to not only restoration of cell function, but also to the activation of multiple detrimental biochemical pathways, leading to secondary energy failure and ultimately, cell death. The formation of reactive oxygen species, nitric oxide and peroxynitrite plays a central role in the development of subsequent neurological damage. In this review we give insight into the pathophysiology of perinatal asphyxia, discuss its clinical relevance and summarize current neuroprotective strategies related to therapeutic hypothermia, ischemic postconditioning and pharmacological interventions. The review will also focus on the possible neuroprotective actions and molecular mechanisms of the selective neuronal and inducible nitric oxide synthase inhibitor 2-iminobiotin that may represent a novel therapeutic agent for the treatment of hypoxic-ischemic encephalopathy, both in combination with therapeutic hypothermia in middle- and high-income countries, as well as stand-alone treatment in low-income countries.

Topics: Allopurinol; Asphyxia Neonatorum; Biotin; Cerebral Palsy; Clinical Trials as Topic; Epilepsy; Erythropoietin; Female; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Intellectual Disability; Ischemic Postconditioning; Melatonin; Neuroprotective Agents; Pregnancy; Reactive Nitrogen Species; Reactive Oxygen Species

Neonatal encephalopathy (NE) is a major cause of neonatal mortality and morbidity. Therapeutic hypothermia (TH) is standard treatment for newborns at 36 weeks of gestation or greater with intrapartum hypoxia-related NE. Term and late preterm infants with moderate to severe encephalopathy show improved survival and neurodevelopmental outcomes at 18 months of age after TH. TH can increase survival without increasing major disability, rates of an IQ less than 70, or cerebral palsy. Neonates with severe NE remain at risk of death or severe neurodevelopmental impairment. This review discusses the evidence supporting TH for term or near term neonates with NE.

Topics: Anesthetics, Inhalation; Biotin; Central Nervous System Depressants; Cerebral Palsy; Constriction; Erythropoietin; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Intellectual Disability; Melatonin; Stem Cell Transplantation; Survival Rate; Umbilical Cord; Xenon