Early axonal and glial pathology in fetal sheep brains with leukomalacia induced by repeated umbilical cord occlusion

We conducted a chronic preparation experiment involving near term fetal she ep to evaluate the contribution of umbilical cord occlusion to fetal brain injury. In experimental groups (n = 11),complete cord occlusion for 3 min f ollowed by 5 min release, repeated 5 times were performed at 3 days after i nitial surgery. Instrumental cases without cord occlusion (n = 3) and unins trumental twins (n = 6) were also examined as controls. Multiple necrotic f oci predominantly in the periventricular white matter were found in the fet al brains examined at 1-3 days after cord occlusion. To estimate the contri bution of early axonal and,glial reaction to brain injury the following imm unohistochemical study was performed. In the lesions, coagulation necrosis, axonal swellings and microglial activation were demonstrated with amyloid precursor protein or ionized calcium binding adapter molecule 1 immunohisto chemistry. The induction of tumor necrosis factor alpha and inducible nitri c oxide synthase were also detected immunohistochemically in the microglia at 1 and 3 days after cord occlusion. In contrast, the reaction of glial fi brillary acidic protein positive astrocytes was faint at I day after occlus ion, but the induction of cyclooxygenase-2 was observed. These findings sug gest the glial reaction of cytokines and free radicals induced by fetal hyp oxia may contribute to the occurrence of brain injury. (C) 1999 Elsevier Sc ience B.V, All rights reserved.