Vascular, Axonal and Glial Pathogenesis of Periventricular Leukomalacia in Fetuses and Neonates

Periventricular leukomalacia (PVL) in prematurely born infants is an important cause of cerebral palsy and intellectual impairment. In the pathogenesis of PVL, both the developing vasculature and differentiating glial progenitor cells within the deep white matter are susceptible to ischemia and very important as predisposing factors. Axonal swellings, which occur as the first signs of PVL, are found in fetuses as well as neonates, and cellular activation secondary to intrauterine infection may also predispose to PVL. Causal factors include cerebral hypoperfusion in the perinatal period, which leads to axonal damage, glutamate release, elevated production of cytokines in microglia and nerve growth factor in astrocytes, and finally an increased plasticity in neurons and oligodendrocytes. Cellular reactivities such as nestin expression following PVL may represent important indicators for determining the effective time for treatment and rehabilitation.