The function of melatonin as a protective agent against newborn hypoxic‐ischemic (H‐I) brain injury is not yet well studied, and the mechanisms by which melatonin causes neuroprotection in neurological diseases are still evolving. This study was designed to investigate whether expression of MT1 receptors is reduced in newborn H‐I brain injury and whether the protective action of melatonin is by alterations of the MT1 receptors. We demonstrated that there was significant reduction in MT1 receptors in ischemic brain of mouse pups in vivo following H‐I brain injury and that melatonin offers neuroprotection through upregulation of MT1 receptors. The role of MT1 receptors was further supported by observation of increased mortality in MT1 knockout mice following H‐I brain injury and the reversal of the inhibitory role of melatonin on mitochondrial cell death pathways by the melatonin receptor antagonist, luzindole. These data demonstrate that melatonin mediates its neuroprotective effect in mouse models of newborn H‐I brain injury, at least in part, by the restoration of MT1 receptors, the inhibition of mitochondrial cell death pathways and the suppression of astrocytic and microglial activation.

中文翻译：

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褪黑素通过MT1受体在新生儿缺氧缺血性脑损伤实验模型中的保护

褪黑素作为针对新生儿缺氧缺血性脑损伤的保护剂的功能尚未得到很好的研究，褪黑素引起神经系统疾病神经保护的机制仍在发展中。这项研究旨在调查新生儿H-1脑损伤中MT1受体的表达是否降低以及褪黑激素的保护作用是否是通过MT1受体的改变引起的。我们证明，在H-1脑损伤后，小鼠幼鼠体内缺血脑中的MT1受体显着减少，褪黑素通过MT1受体的上调提供神经保护作用。观察H-1脑损伤后MT1敲除小鼠死亡率增加以及褪黑激素受体拮抗剂luzindole逆转褪黑激素对线粒体细胞死亡途径的抑制作用，进一步支持了MT1受体的作用。这些数据表明褪黑激素至少在一定程度上通过恢复MT1受体，抑制线粒体细胞死亡途径以及抑制星形胶质细胞和小胶质细胞活化来介导其在新生H-I脑损伤小鼠模型中的神经保护作用。