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Major advances in understanding the cellular mechanisms of brain injury have presented a host of potential targets for intervention. This is particularly true of hypoxic-ischemic injury, the most important form of perinatal brain injury. As the window for effective clinical intervention may be particularly narrow in the fetus and newborn because of the often-delayed and subtle presentation of the onset of the insult, recent focus has been on defining and countering the more delayed mechanisms of brain injury. Recent insights into the mechanisms of oligodendrocyte injury and the role of inflammatory substances in perinatal brain injury are also discussed.