Role of glial cells in periventricular white matter damage in hypoxic neonatal brains

Periventricular white matter (PWM) damage (PWMD) is a common form of brain injury found in survivors of preterm birth and, is the major determinant of neurological morbidity in premature infants. Among various factors predisposing to PWMD hypoxiaischemia remains as the major contributing factor. Hallmark events of PWMD include death of oligodendrocytes, degeneration of axons, hypomyelination, microglial activation and astrogliosis. Activation of microglia and astrocytes in the developing PWM, in response to hypoxic insults, results in excess production of glutamate, free radicals, cytokines along with vascular changes such as increased permeability which are implicated in the pathogenesis of PWMD. In addition, deficiency of antioxidant enzymes in oligodendrocyte progenitor cells renders them highly susceptible to hypoxic damage. The death of oligodendrocytes in hypoxic PWM may result in myelination disturbances. Though the multi-factorial pathogenesis of PWMD is not fully understood, the cross talk between the glial cells reviewed in this chapter could shed some light on the mechanisms mediating oligodendrocyte death in hypoxic PWM.