Pathophysiology of an hypoxic-ischemic insult during the perinatal period

Hypoxia-ischemia is a leading cause of morbidity and mortality in the perinatal period with an incidence of 1/4000 live births. Biochemical events such as energy failure, membrane depolarization, brain edema, an increase of neurotransmitter release and inhibition of uptake, an increase of intracellular Ca(2+), production of oxygen-free radicals, lipid peroxidation, and a decrease of blood flow are triggered by hypoxia-ischemia and may lead to brain dysfunction and neuronal death. These abnormalities can result in mental impairments, seizures, and permanent motor deficits, such as cerebral palsy. The physical and emotional strain that is placed on the children affected and their families is enormous. The care that these individuals need is not only confined to childhood, but rather extends throughout their entire life span, so it is very important to understand the pathophysiology that follows a hypoxic-ischemic insult. This review will highlight many of the mechanisms that lead to neuronal death and include the emerging area of white matter injury as well as the role of inflammation and will provide a summary of therapeutic strategies. Hypothermia and oxygen will also be discussed as treatments that currently lack a specific target in the hypoxic/ischemic cascade.