Role of cytokines in hypoxic periventricular white matter damage in developing brain

Hypoxic-ischemic insults during the perinatal/neonatal period cause damage to the brain particularly the periventricular white matter (PWM) region. Perinatal hypoxia can occur in response to a variety of risk factors such as maternal diabetes, multiple gestation pregnancy or pulmonary and/or cardiac dysfunction in the neonate. Injuries that occur to the developing PWM in response to hypoxia often manifest as severe cognitive and/or motor disturbances over time, and are characterized by death of oligodendrocytes and damage to axons. Such neuropathies are augmented via the production of neuroinflammatory mediators by activated glia as an aftermath of injury. Dysregulated expression of cytokines has been shown to have an important role in mediating hypoxic PWM damage (PWMD). In this chapter, we emphasize on the expression and role of cytokines, especially those which are implicated in hypoxic PWMD, such as interleukin-1β, tumor necrosis factor-α, macrophage colony stimulating factor, interferon-γ, as well as chemokines including monocyte cheomoattractant protein-1. The primary focus of this chapter is on glial cells and the factors that mediate synthesis of cytokines, thereby contributing to neuroinflammatory responses and resulting in death of oligodendrocytes following hypoxic insult.