Original contributionExtracellular glutamate levels and neuropathology in cerebral white matter following repeated umbilical cord occlusion in the near term fetal sheep
Section snippets
Experimental procedures
This study was approved by the Animal Care Committees of the Lawson Research Institute and the University of Western Ontario, in accordance with the guidelines of the Canadian Council on Animal Care.
Results
Results are presented for 14 (7 UCO, 7 controls) of the 20 fetuses. Of the other six animals, two controls had to be euthanized due to poor maternal condition and one fetus died in association with placental bleeding. One UCO fetus developed unexplained metabolic acidemia on day 1 and died. Two of the four fetuses which had 5×4 min UCO on day 2 died from metabolic acidosis following UCO; this led to a change in the protocol to 4×4 min UCO on day 2 for 5 of the UCO animals reported here.
Discussion
This is the first study to describe a correlation between levels of glutamate in the cerebral white matter and the extent of white matter damage in chronically catheterised, unanaesthetised fetuses in utero subjected to repeated UCOs. Fetal white matter damage ranged from extensive injury including severe periventricular necrosis to more diffuse subcortical damage, including reduced myelination, increased apoptosis and an increase in lectin-positive microglia/macrophages. Most significantly we
Conclusion
We have shown for the first time that repeated UCO in the late-gestation, unanaesthetised ovine fetus in utero results in both an increased glutamate efflux in the cerebral white matter and brain damage, with the higher levels of glutamate efflux being associated with more extensive white matter injury. Changes in extracellular glutamate levels must be interpreted with caution at this time as a greater increase in glutamate may reflect a more severe insult as well as reflecting the potential
Acknowledgements
This work was supported by grants from the Medical Research Council of Canada and the National Health and Medical Research Council of Australia. We wish to thank Jac Homan, Susan White, Jhodie Duncan and Mardi Sait for their excellent assistance. We also thank Dr. Bryan Richardson for his interest in these studies.
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