Pub Med Central
Fernando F. Gonzalez, M.D.a and Donna M. Ferriero, M.D.ab
Neonatal brain injury is an important cause of death and disability, with pathways of oxidant stress, inflammation, and excitotoxicity that lead to damage that progresses over a long period of time. Therapies have classically targeted individual pathways during early phases of injury, but more recent therapies such as growth factors may also enhance cell proliferation, differentiation and migration over time. More recent evidence suggests combined therapy may optimize repair, decreasing cell injury while increasing newly born cells.
Causes of early brain injury include stroke, birth trauma, metabolic or genetic disorders, status epilepticus, and asphyxial events. Perinatal asphyxia presents as encephalopathy, or hypoxic ischemic encephalopathy, occurring in 3 to 5 in 1000 live births , while stroke studies conservatively estimate an incidence of 1 in 4000 live births . It is classically thought that hypoxic-ischemic (HI) injury leads to periventricular white matter damage in premature infants, while term infants develop cortical/subcortical lesions , but more recent evidence suggests that this distinction in injury type may not be so clear . While many suffering from perinatal brain injury die during early life, the majority of survivors exhibit neurological deficits that persist, such as cerebral palsy, mental retardation or epilepsy . Aside from hypothermia, no established therapies exist, and treatment and care for the sequelae of early brain injury requires significant resources. Even after maximal care, there is often little improvement in an individual’s overall abilities, with long-term effects on the family, health care system, and society .