Department of Neurosurgery, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Department of Neurosurgery, Jiangsu Province Hospital, China.
Department of Neurosurgery, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Department of Neurosurgery, Jiangsu Province Hospital, China.
Exp Neurol. 2022 Nov;357:114175. doi: 10.1016/j.expneurol.2022.114175. Epub 2022 Jul 19.
Subarachnoid haemorrhage (SAH) is a common and devastating complication of haemorrhagic stroke. SAH is characterised by high mortality rates, permanent disabilities, and is often caused by the rupture of intracranial aneurysms. Low serum triiodothyronine (T3) concentrations have been associated with severe SAH and poor prognosis. T3 has been previously described as an inhibitor of lung fibrosis, and it acts by stimulating autophagy and mitophagy. Here, we indicated in vitro that T3 treatment suppressed neuronal apoptosis by reducing the release of mitochondrial reactive oxygen species (ROS), leading to mitochondrial membrane potential (MMP) decrease. Moreover, this preventative effect was reversed by PINK 1-siRNA treatment. We showed that in vivo T3 treatment promoted mitophagy, decreased microglial activation, alleviated neuroinflammation, and reduced neuronal apoptosis following SAH. Overall, this thyroid hormone (TH) exerts a protective effect on neurones after SAH via the PINK 1/PARKIN pathway. Considering the protective function of TH against neuronal damage, further research can establish TH treatment as a promising and effective therapeutic option for early brain injury (EBI) after SAH.
蛛网膜下腔出血（SAH）是出血性中风的一种常见且具破坏性的并发症。SAH 的死亡率高、永久性残疾，通常是由颅内动脉瘤破裂引起的。血清三碘甲状腺原氨酸（T3）浓度低与严重的 SAH 和不良预后有关。T3 以前被描述为肺纤维化的抑制剂，它通过刺激自噬和线粒体自噬起作用。在这里，我们在体外表明，T3 通过减少线粒体活性氧（ROS）的释放来抑制神经元凋亡，导致线粒体膜电位（MMP）降低。此外，PINK1-siRNA 处理逆转了这种预防作用。我们表明，在体内 T3 治疗可促进线粒体自噬，减少小胶质细胞激活，减轻神经炎症，并减少 SAH 后的神经元凋亡。总的来说，这种甲状腺激素（TH）通过 PINK1/PARKIN 通路对 SAH 后的神经元发挥保护作用。鉴于 TH 对神经元损伤的保护作用，进一步的研究可以确定 TH 治疗作为 SAH 后早期脑损伤（EBI）的一种有前途和有效的治疗选择。
