| Summary: | 碩士 === 國立成功大學 === 藥理學研究所 === 102 === The synthetic glucocorticoid dexamethasone (DEX) has been widely used to prevent or lessen the morbidity of chronic lung disease (CLD) by facilitating surfactant synthesis in pulmonary alveolus in preterm infants. Typically, DEX were administered during a period of life that is critical for the development of the infant brain. There is growing evidence that postnatal DEX therapy will adversely affect the growth and development of the immature brain and is often associated with neurodevelopmental impairment and an increased risk of cerebral palsy. Therefore, growing concern has arisen for the long-term safety of this therapy on the brain development of the child. Although DEX treatment is a powerful way for the prevention and improvement of CLD, but preterm infants are still under the risk of encountering hypoxia-ischemia (HI) condition. Hypoxic–ischemic brain injury in the preterm infant appears selective for white matter, and 10–15% of preterm infants who have suffer from white matter injury subsequently exhibit cerebral palsy, and 50% have cognitive and behavioral deficits. However, the effect of neonatal DEX exposure on HI-induced white matter injury remains unknown. Thus, the objective of this proposal is to investigate the impact of neonatal DEX treatment on HI-induced white matter damage and characterize the possible underlying causes. Using a HI model of premature brain injury, we found that a 3-day tapering course (0.5, 0.3 and 0.1 mg/kg) of DEX treatment in rat pups on postnatal days 1–3 (P1-3) delayed whiter matter development, reduced oligodendrocyte population number and exacerbated HI-induced loss of myelin protein involving MBP, MAG, MOG, PLP in tissues of whiter matter, including cingulum and external capsule. We also found that neonatal DEX treatment exacerbates HI-induced increase in glial fibrillary acidic protein (GFAP) protein expression in the external capsule. In addition, neonatal DEX treatment exacerbates HI-induced microglia activation. Moreover, neonatal DEX treatment exacerbated HI-induced developmental motor deficits before 3-week-old and broken normal neuronal conduction in corpus callosum until 5-week-old. These results revealed that early DEX exposure influence oligodendrocyte lineage growth and delay white matter development and may lead the neonatal brain to be more vulnerable to subsequent HI–induced white matter injury.
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