Abstract
There is only limited morphologic information on long-term alterations and neurotransmitter changes after perinatal asphyxia, and no long-term study showing neurodegeneration has been reported so far. We used an animal model for perinatal asphyxia well documented in the rat to investigate the guinea pig as a species highly mature at birth. Cesarean section was performed on full-term pregnant guinea pigs, and pups, still in membranes, were placed into a water bath at 37°C for asphyxia periods from 2 to 4 min. Thereafter pups were given to surrogate mothers and examined at 3 mo of age. We studied brain areas reported to be hypoxia-sensitive. Neurodegeneration was evaluated by fluoro-jade, neuronal loss by Nissl, reactive gliosis by glial fibrillary acidic protein staining, and differentiation by neuroendocrine-specific protein C immunoreactivity. We tested tyrosine hydroxylase, the vesicular monoamine transporter, and dopamine β-hydroxylase, representing the monoaminergic system; the vesicular acetylcholine transporter; and the excitatory amino acid carrier 1. Neurodegeneration was evident in cerebellum, hippocampal area CA1, and hypothalamus, and neuronal loss could be observed in cerebellum and hypothalamus; gliosis was observed in cerebellum, hippocampus, hypothalamus, and parietal cortex; dedifferentiation was found in hypothalamus and striatum; and monoaminergic, cholinergic, and amino acidergic deficits were shown in several brain regions. The major finding of the present study was that neurodegeneration and dedifferentiation evolved in the guinea pig, a species highly mature at birth. The relevance of this contribution is that a simple animal model of perinatal asphyxia resembling the clinical situation of intrauterine hypoxia-ischemia and presenting with neurodegeneration was characterized.
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Abbreviations
- PA:
-
perinatal asphyxia
- vMAT:
-
vesicular monoamine transporter
- DBH:
-
dopamine β-hydroxylase
- TH:
-
tyrosine hydroxylase
- EAAC1:
-
excitatory amino acid carrier 1
- vAChT:
-
vesicular acetylcholine transporter
- FJ:
-
fluoro-jade
- GFAP:
-
glial fibrillary acidic protein
- NSP-C:
-
neuroendocrine-specific protein C
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Acknowledgements
We thank Prof. Dr. Gert Lubec, FRSC (UK) for scientific advice.
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Financial support by the Red Bull Company, Salzburg, Austria.
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Bernert, G., Hoeger, H., Mosgoeller, W. et al. Neurodegeneration, Neuronal Loss, and Neurotransmitter Changes in the Adult Guinea Pig with Perinatal Asphyxia. Pediatr Res 54, 523–528 (2003). https://doi.org/10.1203/01.PDR.0000081760.48331.7A
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DOI: https://doi.org/10.1203/01.PDR.0000081760.48331.7A
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