US EPA

1785251 

Journal Article 

Brain damage and hypoxia in an ovine fetal chronic cocaine model 

Laurini, RN; Arbeille, B; Fignon, A; Locatelli, A; Maulik, D; Arbeille, P 

1995 

1 

Journal of Maternal-Fetal Investigation
ISSN: 0939-6322 

DART/TER/95003077 

5 

3 

191 

English 

The objective was to assess the fetal neuropathological findings in pregnant ewes treated with cocaine from day 65 to day 132 of gestation. The study group received daily 140 mg (n = 7) of cocaine intramuscularly and the control group (n = 5) IM placebo. Surgery, hypoxic tests (cord compression (3 mn) - 15 mn resting period-maternal aorta compression (1 mn)) and haemodynamic measurements (cerebral and umbilical Doppler) were carried out at 90 and 134 days of gestation. All pregnancies were interrupted by cesarean section at day 134. Brains were obtained immediately after surgery, samples (cortex, white matter, germinal matrix) were fixed for electron microscopy and the rest immersion-fixed in a buffered formaldehyde-glacial acetic acid solution. Following gross examination standard samples were embedded in paraffin and stained with haematoxylin-eosin and glial fibrillary acidic protein for histology. The main lesions were focal grey matter necrosis, diffuse perivascular oedema and focal perivascular haemorrhages. Electron microscopy was particularly helpful in defining changes of perivascular oedema and neuronal degeneration. In addition preliminary studies showed the presence of pathological gliosis. All these morphological findings were significantly more important in the study group. On the other hand the Doppler investigations of the fetus at 134 day (delivery) showed a reduction of the utero placental flow and a redistribution of the fetal flows toward the brain in response to a moderate hypoxia (blood gazes at 134 day). The fetal weight in the study group was significantly lower than in the control group. The present findings show that repeated cocaine induces a fetal growth retardation with a moderate hypoxia which could be responsible for the brain ischemic lesions. 

Pregnancy; Cocaine/TOXICITY; Fetus/DRUG EFFECTS; Brain/DRUG EFFECTS; Brain/PATHOLOGY; Fetal Anoxia/CHEMICALLY INDUCED; 50-36-2