Brain damage and hypoxia in an ovine fetal chronic cocaine model

Objective: To assess the development of brain damage in an ovine fetal chro nic cocaine model. To evaluate the effect of isolated hypoxic tests on this model and to correlate hemodynamic findings (brain-sparing effect) followi ng fetal hypoxia and the occurrence of brain damage. Study design: Fifteen ewes were divided into a control group (n=7) and a cocaine treated group (n =8). From day 65 to day 134 the cocaine treated animals received a daily (5 days per week) intramuscular injection (2 mg/kg cocaine) and the control a nimals a placebo injection (2 mi of isotonic solution). Both groups underwe nt hypoxic tests (cord compression (3 min) and aortic compression (1 min)) at 90 and 134 days. In addition, anesthesia for magnetic resonance imaging (MRI) examination was carried out at 125 days. Fetal blood samples were col lected during both series of hypoxic tests and the cerebral and umbilical f lows were monitored by Doppler. Samples from 25 brains (control n=10; cocai ne n=15) were processed for light and electron microscopic examination. Qua ntification of brain damage was done on semithin sections from six areas of cortex and germinal matrix on each fetus. Results: Similar forms of brain damage (selective neuronal loss limited to the parasaggital cortex, striatu m, hippocampus and Purkinje cells) was present in both groups but lesions w ere more frequent in the cocaine treated group as shown by quantitative ana lysis for the proportion of abnormal capillaries (65% vs. 35%), capillary e dema (61% vs. 34%) and abnormal neurons showing delayed neuronal degenerati on (DND) (66% vs. 36%) in the cocaine and control group respectively. There was no significant difference in immunoreactivity for glial fibrillary aci dic protein (GFAP) but it was more marked in the cerebellum of cocaine trea ted animals. Fetal blood samples showed a moderate sustained hypoxia and Do ppler findings demonstrated the presence of a brain sparing effect associat ed with increased uterine and umbilical vascular resistance in the cocaine treated group. Nevertheless, the amplitude of the heart rate increase and c erebral dilatation was significantly lower in the cocaine treated animals. Conclusion: This ovine fetal chronic cocaine model showed the presence of b rain damage. Cocaine treatment seems to potentiate the effect of the hypoxi c tests. Independent of the cause, the brain damage developed in the presen ce of brain sparing effect, strongly suggesting that this phenomenon is a s ign of a pathological fetal condition and no guarantee that it will prevent tissue damage. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.