Early immunohistochemical detection of axonal damage and glial activation in extremely immature brains with periventricular leukomalacia.

Extremely low birth weight (ELBW) infants, who died at 12 hours to 7 days after birth, with periventricular leukomalacia (PVL), were examined by means of neuropathological and immunohistochemical methods. Fourteen infants without PVL were used as controls. Anti-beta-amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba1) antibodies were used as markers for axonal damage, reactive astrocytes and activated microglia, respectively. Thirteen of 14 ELBW infants with PVL showed a widespread distribution of leukomalacia and 10 showed postnatal-onset of leukomalacia. In 12 of the 14 infants with PVL, regions of APP-reactive axons were found multifocally in the cerebral white matter, but 8 of them did not show coagulation necrosis on HE staining. GFAP-positive cells and Iba1-positive cells were markedly found in the white matter of all cases with PVL and slightly in all 14 controls. These results indicated that in ELBW infants, the distribution and formation of PVL foci are widespread and characteristic and so may involve motor and intellectual abilities in ELBW infants. Therefore, the perinatal management to maintain an appropriate cerebral circulation and oxygenation may be very important.