Abstract
The striatum, richly innervated by the nigrostriatal dopaminergic pathway, is a brain region highly vulnerable to ischemic/hypoxic neuronal damage and especially affected by repetitive insults. The present study tests the hypothesis that recurrent asphyxia/reventilation alters extracellular dopamine (DA) by decreasing cerebral cortical oxygenation in the striatum of newborn piglets. Anesthetized, ventilated piglets (n=7) underwent seven repeated episoces of 3 min asphyxia, each followed by 15 min reventilation/recovery. Cortical O2 pressure, phosphorescence quenching, and extracellular striatal DA. by in vivo microdialysis, were measured continuously. Serum lactate levels increased from 4±3 mM/L (baseline) to 16±1 mM/L after the 7th episode of asphyxia/ reventilation. Cortical O2 pressure decreased from 39±9 Torr (baseline) to 11±6 Torr during each asphyxia then rapidly returned to baselne values, except after the 7th asphyxia when it returned to baseline in 10 min then decreased again to 19±4 Torr. Extracellular DA concentration was dependent on the number of asphyxia episodes and was higher after each successive asphyxia. From the 2nd to 7th asphyxia, extracellular DA increased from baseline of 6.5 to 9, 12.6. 26, 57, and 84 pmoles/ml, respectively. During 15 min reventilation. DA returned to baseline levels for the first 5 asphyxias, but after the 6th and 7th episodes, DA remained higher than baseline by 50-70%. This progressive DA accumulation could result from hypoxia-induced DA release or from impaired DA reuptake and/or degradation. Thus, repeated episodes of asphyxia were associated with progressive disturbance of striatal DA metabolism, leading to high levels af extracellular DA which represent a potential mechanism of post-asphyxial striatal neuronal injury. Funded by NIH #HD-20337.
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Goplerud, J., Huang, CC., Yonetani, M. et al. 79 EFFECT OF REPEATED ASPHYXIA/REVENTRATION ON STRIATAL DOPAMINE RELEASE AND CEREBRAL CORTICAL OXYGEN PRESSURE IN NEWBOFN PIGLETS. Pediatr Res 36, 16 (1994). https://doi.org/10.1203/00006450-199407000-00079
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DOI: https://doi.org/10.1203/00006450-199407000-00079
