Title:
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The pathophysiological consequences of an in utero hypoxic insult on the foetal rat brain
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The aim of this study was to investigate the effects of an in utero hypoxic insult on the near-term foetal rat brain. An hypoxic insult of 10, 20 or 30 minutes was created by clamping the utero-placental vessels of one uterine horn in an anaesthetised pregnant Lister hooded rat at 22 days gestation. After completion of the occlusion period the dam was killed and the foetal rats were delivered by Caesarian section and resuscitated. Alternatively the clamps were removed, the uterine horn placed back inside the dam and the wound sutured. After a recovery period of 20 minutes, during which time the dam was not anaesthetised, the dam was killed and the foetal rats were delivered by Caesarian section and resuscitated. Biochemical analysis of homogenised and deproteinised brain tissue samples from the neonatal rats showed a level of metabolic deficit typically associated with irreversible neuronal necrosis in adult models of hypoxicischaemia. The level of brain tissue in rats subjected to a 30 minute clamp without recovery was 19.77± 0.8nmols/mg brain tissue whereas in control rats the level of lactate was 7.98 ± 0.2nmols/mg brain tissue (p < 0.001). Brain tissue ATP declined by more than 80% from 2.67 ± 0.2nmols/mg brain tissue in control rats to 0.59 ± 0.1nmols/mg brain tissue in hypoxic rats (p < 0.001). Other metabolites also showed changes consistent with a major hypoxic insult. This study has shown that despite a significant metabolic deficit those rats which survive an in utero hypoxic insult suffer only limited and discrete neuropathological changes and no apparent long-term physiological or cognitive deficits. These results suggest that the near-term foetal rat brain has a high level of resistance to the long term consequences of a severe hypoxic insult.
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