Department of Paediatrics, Copenhagen University Hospital, Rigshospitalet, Juliane Marie Center, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Eur J Paediatr Neurol. 2011 Nov;15(6):465-77. doi: 10.1016/j.ejpn.2011.05.002. Epub 2011 May 31.
Glucocorticoids are commonly used in treatment of paediatric diseases, but evidence of associated adverse cerebral effects is accumulating. The various pharmacokinetic profiles of the exogenous glucocorticoids and the changes in pharmacodynamics during childhood, result in different exposure of nervous tissue to exogenous glucocorticoids. Glucocorticoids activate two types of intracellular receptors, the mineralocorticoid receptor and the glucocorticoid receptor. The two receptors differ in cerebral distribution, affinity and effects. Exogenous glucocorticoids favor activation of the glucocorticoid receptor, which is associated with unfavorable cellular outcomes. Prenatal treatment with glucocorticoids can compromise brain growth and is associated with periventricular leukomalacia, attentions deficits and poorer cognitive performance. In the neonatal period exposure to glucocorticoids reduces neurogenesis and cerebral volume, impairs memory and increases the incidence of cerebral palsy. Cerebral effects of glucocorticoids in later childhood have been less thoroughly studied, but apparent brain atrophy, reduced size of limbic structures and neuropsychiatric symptoms have been reported. Glucocortioids affect several cellular structures and functions, which may explain the observed adverse effects. Glucocorticoids can impair neuronal glucose uptake, decrease excitability, cause atrophy of dendrites, compromise development of myelin-producing oligodendrocytes and disturb important cellular structures involved in axonal transport, long-term potentiation and neuronal plasticity. Significant maturation of the brain continues throughout childhood and we hypothesize that exposure to exogenous glucocorticoids during preschool and school age causes adverse cerebral effects. It is our opinion that studies of associations between exposure to glucocorticoids during childhood and impaired neurodevelopment are highly relevant.
糖皮质激素常用于治疗儿科疾病，但越来越多的证据表明其会对大脑产生不良影响。外源性糖皮质激素的各种药代动力学特征和儿童期药效动力学的变化，导致神经组织对外源性糖皮质激素的不同暴露。糖皮质激素激活两种类型的细胞内受体，即盐皮质激素受体和糖皮质激素受体。这两种受体在大脑中的分布、亲和力和作用不同。外源性糖皮质激素有利于激活糖皮质激素受体，这与不利的细胞后果有关。产前接受糖皮质激素治疗会影响大脑生长，与脑室周围白质软化、注意力缺陷和认知表现较差有关。在新生儿期接触糖皮质激素会减少神经发生和脑容量，损害记忆，并增加脑瘫的发病率。糖皮质激素对儿童后期大脑的影响研究得还不够充分，但据报道，明显的脑萎缩、边缘结构缩小和神经精神症状。糖皮质激素影响几种细胞结构和功能，这可能解释了观察到的不良影响。糖皮质激素可损害神经元葡萄糖摄取，降低兴奋性，导致树突萎缩，损害髓鞘形成少突胶质细胞的发育，并干扰参与轴突运输、长时程增强和神经元可塑性的重要细胞结构。大脑在整个儿童期仍在不断成熟，我们假设在学龄前和学龄期暴露于外源性糖皮质激素会导致大脑不良影响。我们认为，研究儿童期暴露于糖皮质激素与神经发育受损之间的关系具有重要意义。
