Baud Olivier, Gressens Pierre
AP-HP, service de Réanimation et pédiatrie néonatales, hôpital Robert Debré, 48, boulevard Sérurier, 75019 Paris, France. Inserm Avenir R05230HS, Paris, France.
Med Sci (Paris). 2009 Aug-Sep;25(8-9):713-7. doi: 10.1051/medsci/2009258-9713.
Corticosteroids have been used for the past 20-30 years to prevent lethal consequences of pulmonary and cerebral disorders linked to prematurity. However, many data suggest a low risk-benefit ratio, and the long-term emergence of adverse neurodevelopmental outcomes objectivated by RMN studies. Although multiple mechanisms have been proposed to explain GCs effects on brain development, none has clearly emerged so far. A breakthrough study has been recently published, which identified the sonic hedgehog (Shh) signaling pathway as the target of Gcs action. Shh is a crucial regulator of brain development and neural stem/progenitor cells, and GCs suppress Shh-induced proliferation of cerebellar progenitor cells ; Shh acts through the induction of the enzyme 11betaHSD2, which inactivates the GCs corticosterone and prednisolone, but not dexamethasone. These data should lead to the development of novel molecules (either GC or Shh agonists) both -efficient and neuroprotective.
在过去20到30年里，皮质类固醇一直被用于预防与早产相关的肺部和脑部疾病的致命后果。然而，许多数据表明其风险效益比很低，并且磁共振成像（MRI）研究证实了长期存在不良神经发育结局。尽管已经提出了多种机制来解释糖皮质激素（GCs）对大脑发育的影响，但目前尚未明确哪种机制。最近发表了一项突破性研究，该研究确定音猬因子（Shh）信号通路是GCs作用的靶点。Shh是大脑发育和神经干/祖细胞的关键调节因子，GCs可抑制Shh诱导的小脑祖细胞增殖；Shh通过诱导11β-羟基类固醇脱氢酶2（11betaHSD2）发挥作用，该酶可使GCs皮质酮和泼尼松龙失活，但对地塞米松无此作用。这些数据应会促使开发出高效且具有神经保护作用的新型分子（GCs或Shh激动剂）。
