%0 Journal Article
%T The Role of Cytokines and Inflammatory Cells in Perinatal Brain Injury
%A Ryan M. McAdams
%A Sandra E. Juul
%J Neurology Research International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/561494
%X Perinatal brain injury frequently complicates preterm birth and leads to significant long-term morbidity. Cytokines and inflammatory cells are mediators in the common pathways associated with perinatal brain injury induced by a variety of insults, such as hypoxic-ischemic injury, reperfusion injury, toxin-mediated injury, and infection. This paper examines our current knowledge regarding cytokine-related perinatal brain injury and specifically discusses strategies for attenuating cytokine-mediated brain damage. 1. Introduction Preterm birth affects 12.5% of pregnancies in the United States [1, 2] and is the leading cause of neonatal morbidity and mortality, accounting for nearly half of the long-term neurologic morbidity in children [3]. The majority of premature infants in developed countries survive; however, 5¨C10% of survivors develop cerebral palsy (CP), and 40¨C50% develop cognitive and behavioral deficits [4, 5]. The prolonged vulnerability of the developing white and gray matter to excitotoxic, oxidative, and inflammatory forms of injury is a major factor in the pathogenesis of perinatal brain injury. While acute catastrophic brain injuries sometime occur (e.g., severe intraparenchymal hemorrhage), injury to white and gray matter regions is most often the cumulative result of metabolic, infectious and/or inflammatory, and hypoxic-ischemic insults over time [6]. For example, early respiratory compromise and systemic hypotension can precipitate glutamate, free radical, and cytokine toxicity to developing oligodendrocytes and neurons. The clinical course might be further complicated by late-onset or necrotizing enterocolitis (NEC). These sequential events result in different topographic patterns of injury based on developmental and genetic susceptibilities. Although there has been much focus on white matter injury (WMI) in premature infants, gray matter abnormalities in cortical and deep nuclear structures, and cerebellar injuries are also common and likely contribute to development of cognitive delay, psychomotor delay, and CP [7]. A variety of inciting events such as hypoxic-ischemia, infection, and/or inflammation, can stimulate a cascade of secondary responses, including fluid-electrolyte imbalance, regional blood flow alterations, calcium-mediated cellular injury, free-radical generation, oxidative and nitrosative stress, glutamate-induced excitotoxicity, disturbances in proinflammatory cytokine production, mitochondrion function, and apoptotic cell death [6, 8]. These disturbances result in activation of inflammatory cells involved in the
%U http://www.hindawi.com/journals/nri/2012/561494/