The involvement of thyroid hormones and related molecules in neuroprotective mechanisms in the developing brain.

新生儿缺氧缺血性脑病（HIE）是新生儿期神经退行性变和死亡的主要原因之一。虽然低氧预处理（HPC）在动物模型中对HIE具有较强的神经保护作用，但其机制尚不完全清楚，尤其是在未成熟脑中。在这里，我们调查是否甲状腺激素（TH），这是必不可少的正常大脑发育过程中，有助于HPC的神经保护机制，通过使用一个既定的模型HPC在新生大鼠。在出生后第6天（P6）对未成熟大鼠进行HPC处理（8%O2，37°C，2.5 h）。随后，我们研究了TH，TH受体（TRs）和2型和3型脱碘酶（D2和D3）mRNA的水平，和髓鞘碱性蛋白（MBP）在HPC处理后24小时在P7。HPC处理后24小时，在发育中的大鼠脑中，局部三碘甲状腺原氨酸（T3）水平上调，可能是通过上调D2。此外，T3的下游蛋白MBP的表达在HPC处理后24 h显著增加。本研究表明，甲状腺激素及其相关分子可能在发育期的神经保护机制中发挥重要作用。

Neonatal hypoxic〓ischemic encephalopathy (HIE) is one of the major causes of neurodegeneration and mortality in the neonatal period. Although hypoxic preconditioning (HPC) provided strong neuroprotection against HIE in an animal model, the mechanism underlying this effect is not fully understood especially in the immature brain. Here, we investigated whether thyroid hormones (THs), which are essential during normal brain development, contribute to the neuroprotective mechanisms of HPC by using an established model of HPC in neonatal rats. HPC treatment (8% O2 for 2.5 h at 37°C) was performed in immature rats at postnatal day6 (P6). Subsequently, we investigated the levels of THs, TH receptors (TRs) and type2 and 3 deiodinases (D2 and D3) mRNA, and myelin basic protein (MBP) at 24 h after HPC treatment at P7. The local level of triiodothyronine (T3) was upregulated 24 h after HPC treatment in the developing rat brain, probably via the upregulation of D2. In addition, the expression of MBP, which is the downstream protein of T3, was significantly increased 24 h after HPC treatment. The present study indicates that thyroid hormones and their associated molecules may play a significant role in neuroprotective mechanisms during the developmental period.