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Brain damage and hypoxia in an ovine fetal chronic cocaine model

Laurini, Ricardo LU ; Arbeille, B; Gemberg, C; Akoka, S; Locatelli, A; Lansac, J and Arbeille, P (1999) In European Journal of Obstetrics, Gynecology, and Reproductive Biology 86(1). p.15-22
Abstract
OBJECTIVE: To assess the development of brain damage in an ovine fetal chronic cocaine model. To evaluate the effect of isolated hypoxic tests on this model and to correlate hemodynamic findings (brain-sparing effect) following 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 animals a placebo injection (2 ml of isotonic solution). Both groups underwent hypoxic tests (cord compression (3 min) and aortic compression (1 min)) at 90 and 134 days. In addition, anesthesia for magnetic resonance imaging... (More)
OBJECTIVE: To assess the development of brain damage in an ovine fetal chronic cocaine model. To evaluate the effect of isolated hypoxic tests on this model and to correlate hemodynamic findings (brain-sparing effect) following 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 animals a placebo injection (2 ml of isotonic solution). Both groups underwent 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 collected during both series of hypoxic tests and the cerebral and umbilical flows were monitored by Doppler. Samples from 25 brains (control n = 10; cocaine n= 15) were processed for light and electron microscopic examination. Quantification 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, striatum, hippocampus and Purkinje cells) was present in both groups but lesions were more frequent in the cocaine treated group as shown by quantitative analysis for the proportion of abnormal capillaries (65% vs. 35%), capillary edema (61% vs. 34%) and abnormal neurons showing delayed neuronal degeneration (DND) (66% vs. 36%) in the cocaine and control group respectively. There was no significant difference in immunoreactivity for glial fibrillary acidic protein (GFAP) but it was more marked in the cerebellum of cocaine treated animals. Fetal blood samples showed a moderate sustained hypoxia and Doppler findings demonstrated the presence of a brain sparing effect associated with increased uterine and umbilical vascular resistance in the cocaine treated group. Nevertheless, the amplitude of the heart rate increase and cerebral dilatation was significantly lower in the cocaine treated animals. CONCLUSION: This ovine fetal chronic cocaine model showed the presence of brain damage. Cocaine treatment seems to potentiate the effect of the hypoxic tests. Independent of the cause, the brain damage developed in the presence of brain sparing effect, strongly suggesting that this phenomenon is a sign of a pathological fetal condition and no guarantee that it will prevent tissue damage. (Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Brain damage, Flow redistribution, Sheep, Hypoxia, Chronic cocaine model
in
European Journal of Obstetrics, Gynecology, and Reproductive Biology
volume
86
issue
1
pages
15 - 22
publisher
Elsevier
external identifiers
  • pmid:10471137
  • scopus:0032810587
ISSN
0301-2115
DOI
10.1016/S0301-2115(99)00036-6
language
English
LU publication?
no
id
ee8e1045-02cc-4909-8af4-b00aa0e714e3 (old id 1116041)
date added to LUP
2008-07-09 14:27:05
date last changed
2017-01-29 03:33:40
@article{ee8e1045-02cc-4909-8af4-b00aa0e714e3,
  abstract     = {OBJECTIVE: To assess the development of brain damage in an ovine fetal chronic cocaine model. To evaluate the effect of isolated hypoxic tests on this model and to correlate hemodynamic findings (brain-sparing effect) following 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 animals a placebo injection (2 ml of isotonic solution). Both groups underwent 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 collected during both series of hypoxic tests and the cerebral and umbilical flows were monitored by Doppler. Samples from 25 brains (control n = 10; cocaine n= 15) were processed for light and electron microscopic examination. Quantification 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, striatum, hippocampus and Purkinje cells) was present in both groups but lesions were more frequent in the cocaine treated group as shown by quantitative analysis for the proportion of abnormal capillaries (65% vs. 35%), capillary edema (61% vs. 34%) and abnormal neurons showing delayed neuronal degeneration (DND) (66% vs. 36%) in the cocaine and control group respectively. There was no significant difference in immunoreactivity for glial fibrillary acidic protein (GFAP) but it was more marked in the cerebellum of cocaine treated animals. Fetal blood samples showed a moderate sustained hypoxia and Doppler findings demonstrated the presence of a brain sparing effect associated with increased uterine and umbilical vascular resistance in the cocaine treated group. Nevertheless, the amplitude of the heart rate increase and cerebral dilatation was significantly lower in the cocaine treated animals. CONCLUSION: This ovine fetal chronic cocaine model showed the presence of brain damage. Cocaine treatment seems to potentiate the effect of the hypoxic tests. Independent of the cause, the brain damage developed in the presence of brain sparing effect, strongly suggesting that this phenomenon is a sign of a pathological fetal condition and no guarantee that it will prevent tissue damage.},
  author       = {Laurini, Ricardo and Arbeille, B and Gemberg, C and Akoka, S and Locatelli, A and Lansac, J and Arbeille, P},
  issn         = {0301-2115},
  keyword      = {Brain damage,Flow redistribution,Sheep,Hypoxia,Chronic cocaine model},
  language     = {eng},
  number       = {1},
  pages        = {15--22},
  publisher    = {Elsevier},
  series       = {European Journal of Obstetrics, Gynecology, and Reproductive Biology},
  title        = {Brain damage and hypoxia in an ovine fetal chronic cocaine model},
  url          = {http://dx.doi.org/10.1016/S0301-2115(99)00036-6},
  volume       = {86},
  year         = {1999},
}