Genzo Marumo

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 sheep to evaluate the contribution of umbilical cord occlusion to fetal brain injury. In experimental groups (n = 11), complete cord occlusion for 3 min followed by 5 min release, repeated 5 times were performed at 3 days after initial surgery. Instrumental cases without cord occlusion (n = 3) and uninstrumental twins (n = 6) were also examined as controls. Multiple necrotic foci predominantly in the periventricular white matter were found in the fetal brains examined at 1-3 days after cord occlusion. To estimate the contribution of early axonal and glial reaction to brain injury the following immunohistochemical study was performed. In the lesions, coagulation necrosis, axonal swelling and microglial activation were demonstrated with amyloid precursor protein or ionized calcium binding adapter molecule 1 immunohistochemistry. The induction of tumor necrosis factor alpha and inducible nitric oxide synthase were also detected immunohistochemically in the microglia at 1 and 3 days after cord occlusion. In contrast, the reaction of glial fibrillary acidic protein positive astrocytes was faint at 1 day after occlusion, but the induction of cyclooxygenase-2 was observed. These findings suggest the glial reaction of cytokines and free radicals induced by fetal hypoxia may contribute to the occurrence of brain injury.

Generation of Periventricular Leukomalacia by Repeated Umbilical Cord Occlusion in Near-Term Fetal Sheep and Its Possible Pathogenetical Mechanisms

Periventricular leukomalacia (PVL) is a major cause of cerebral palsy. However, pathogenetic mechanisms of PVL have not been fully understood. Although it has been postulated that umbilical cord compression is related to the development of PVL, no animal experiments clearly demonstrated an association of umbilical cord occlusion with ‘periventricular’ white matter lesions. The purpose of this study is to determine whether umbilical cord occlusions could produce periventricular white matter lesions in fetal sheep and to examine how changes in fetal cardiovascular and metabolic variables are related to the induction of brain damage. Fourteen near-term fetal sheep underwent umbilical cord occlusion (3-min total cord occlusions 5 times at 5-min intervals). Dissections performed 24 h after cord occlusion revealed that periventricular white matter lesions were produced in 7 out of 14 sheep fetuses. According to the pattern of brain damage, we classified the fetal sheep into three groups: 5 fetuses with dominant lesions in the periventricular white matter (group I), 4 fetuses with brain lesions in the cerebral cortex and thalamus (group II) and 5 fetuses with no or minimal brain lesions (group III). Group I showed higher blood pressure and higher plasma lipid peroxide levels before cord occlusion compared to the other groups, while group II showed systemic hypotension during cord occlusion. No significant differences in changes in pH, PaCO2, PaO2 and heart rate were found between the three groups. It is speculated that PVL might be produced by an association of preexisting chronic circulatory instability with an acute episode of severe repetitive cord occlusion.

A case of fetal vesicoallantoic cyst in the umbilical cord.

A vesicoallantoic cyst in the umbilical cord was detected by fetal ultrasonography at 16 weeks of gestation. The blood flow through the umbilical vessels was evaluated with periodic color Doppler ultrasonographic examinations because compression by the cyst may cause reduction in blood flow and lead to fetal death. After disappearance of the cyst, the infant was delivered vaginally. Retrograde cystography revealed a narrow channel between the bladder and the navel, confirming patent urachus, which was resected without any complications.

Visualization of the endometrium by intrauterine sonography.

Thirty‐five women with normal menstrual cycles underwent transvaginal and high‐frequency (15‐ or 20‐MHz) intrauterine sonographic examinations for the assessment of the endometrium. Five sonographic patterns of endometrium were recognized by both sonographic techniques, but the pattern visualized differed between techniques in 9 women (26%). The higher resolution of intrauterine sonography provided more detail of the endometrium. Our preliminary experience indicates that high‐frequency intrauterine sonography enables more detailed visualization of changes in the endometrium during the menstrual cycle than does transvaginal sonography.