2P-S3-2

PATHOGENESIS AND PREVENTION OF PERIVENTRICULAR LEUKOMALACIA AND PONTOSUBICULAR NECROSIS

Takashima S
National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan

Fetal and neonatal hypoxic-ischemic encephalopathy is an important cause of cerebral palsy and intellectual impairment. There are several types of perinatal brain damage as to its localized distribution due to kinds of hypoxic-ischemic causes and brain maturity. Their pathogenesis may be different in each type. Periventricular leukomalacia (PVL) occurs in the deep white matter of preterm infants, and ponto- subicular necrosis (PSN) in the pontine nuclei and subiculum of preterm and term neonate brains.

In the pathogenesis on PVL, the development of cerebral vasculature and the differentiation of glial cells in deep white matter is very important as predisposing factors. As causal factors, the cerebral hypoperfusion in perinatal period causes axonal damage, release glutamate, increase cytokine in microglia and nerve growth factor in astrocyte, and finally induces plasticity in neurons and oligodendrocytes. These cellar reactivation after PVL may be important to determine effective time of treatment and rehabilitation.

In neuropathology of neonates, there is another important lesion, PSN, which is characterized by neuronal karyorrhexis in the pontine nucleus and subiculum of perinatal brains aged from 28 weeks of gestation to 2 months after birth. This PSN has rather the characters of apoptosis such as karyorrhexis, cellular atrophy and few glial reaction. The developmental discrepancy between neurons exhibiting late maturation and vessels showing an early increase in the basis pontis and subiculum may predispose fetuses and neonates to the production of PSN. As causal factors, ischemia, hyperogygenemia and hypocarbia are reported. Nestin, abundant in multipotential stem cells, is reactivated in sur- rounding cells of the subacute and chronic lesions. Thus, local plasticity may be activated both in necrotic and apoptotic cell death, and important for treatment.