کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6018527 | 1186520 | 2012 | 13 صفحه PDF | دانلود رایگان |
While neonatal caffeine treatment is commonly used to alleviate apnea of prematurity in neonates and to improve neurological outcomes, its effects on adenosine A1 and A2A receptors (A1-R and A2A-R) are poorly known. We hypothesized that the central pharmacological action of caffeine is mediated by modification of the postnatal development of the adenosinergic system during a critical period. On postnatal days 2-6 (P2-P6) two groups of newborn rats were orally administered water plus glucose and/or caffeine at therapeutic doses to mimic the clinical use of caffeine in human neonates. Cardio-respiratory parameters were measured and the presence of A1-R and A2A-R and c-Fos protein was identified immunohistochemically in animals sacrificed from P2 to P11. % Haemoglobin saturation, and hearth and breath rates were significantly increased in caffeine-treated group (P5-P6). Significant differences were identified in the relative gene expression of A1-R and A2A-R, with an increase of A1-R labeling in the anterior hypothalamic area, ventromedial hypothalamic nucleus, parabrachial complex and ventrolateral medulla of the caffeine-treated group at P6. A moderate increase in A2A-R labeling was observed in ponto-medullary nuclei and other hypothalamic areas. An increase in c-Fos-positive labeled cells was found in the caffeine-treated group at P5-P6 within the same areas described above, with the most clear-cut increase seen in the arcuate nucleus. Indeed, increased A1-R and A2A-R gene expression was observed in both the brainstem and hypothalamus at P5. Up-regulation of adenosinergic maturation in central cardio-respiratory areas in caffeine-treated neonatal rats could explain the pharmacological effects of caffeine observed in premature infants.
⺠The apnea of the premature infant is treated with caffeine. ⺠There is a relation of the maturation of adenosinergic system with apneas. ⺠Caffeine promotes an earlier maturation of adenosinergic system. ⺠Postnatal intake of caffeine up-regulates A1 and A2A receptors in neonatal brain. ⺠The changes could explain the clinical caffeine effects observed in newborn apnea.
Journal: Experimental Neurology - Volume 237, Issue 2, October 2012, Pages 247-259