Periventricular Leukomalacia Neurobiology. Volpe JJ. Boston MA.

Periventricular leukomalacia (PVL) is the major neuropathological form of brain injury in premature infants. The pathogenesis of this lesion relates to 3 major interacting factors: incomplete development of the vascular supply to the cerebral white matter, maturation-dependent impairment in regulation of cerebral blood flow, and vulnerability of oligodendroglial (OL) precursor cells to attack by free-radicals. This free-radical attack is potentiated by increases in local iron concentration as can be seen with intraventricular hemorrhage. Inflammatory cytokines from maternal / fetal infection play a contributory role in the pathogenesis of PVL through a variety of different mechanisms. Increased extracellular glutamate from ishemia / reperfusion is toxic to OL precursor cells due to activation of the AMPA/kainate receptors. Potential preventative interventions include: screening for impaired cerebral autoregulation using near-infrared spectroscopy, use of free-radical scavengers to prevent toxicity by reactive oxygen species, administration of AMPA/kainate receptor antagonists to prevent glutamate-mediated injury, and the use of maternal antibiotics or anti-cytokine agents to prevent toxicity from inflammatory cytokines.