Department of Anesthesiology, The first Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, China.
Department of Neurosurgery, The first Affiliated Hospital of Bengbu Medical University, Bengbu, 233004, China.
Neurosurg Rev. 2024 Oct 8;47(1):741. doi: 10.1007/s10143-024-02879-y.
Subarachnoid hemorrhage (SAH) has high mortality. Early brain injury (EBI) is responsible for unfavorable outcomes for patients with SAH. The protective involvement of autophagy in hemorrhagic stroke has been proposed. The transcription factor EB (TFEB) can increase autophagic flux by promoting autophagosome formation and autophagosome-lysosome fusion, and dysregulation of TFEB activity might induce the development of several diseases. However, the biological functions of TFEB in EBI after SAH remain unknown. We established an animal model of SAH by the modified endovascular perforation method. Expression of TFEB and autophagy required genes was measured by western blotting and immunofluorescence staining. SAH grading, brain water content and neurobehavioral functions were evaluated at 24 h post-SAH. Neuronal apoptosis in cerebral cortex was assessed by TUNEL staining and Fluoro Jade B staining. TFEB was downregulated in SAH rats, and its overexpression reduced brain edema and ameliorated neurological deficits of SAH rats. Additionally, the neuronal apoptosis induced by SAH was inhibited by TFEB overexpression. Moreover, TFEB overexpression promoted autophagy after SAH. TFEB overexpression promotes autophagy to inhibit neuronal apoptosis, brain edema and neurological deficits post-SAH.
蛛网膜下腔出血 (SAH) 死亡率高。早期脑损伤 (EBI) 是导致 SAH 患者预后不良的原因。自噬在出血性中风中具有保护作用。转录因子 EB (TFEB) 可以通过促进自噬体形成和自噬体-溶酶体融合来增加自噬流,TFEB 活性的失调可能会引发多种疾病的发展。然而,TFEB 在 SAH 后的 EBI 中的生物学功能尚不清楚。我们通过改良的血管内穿孔方法建立了 SAH 动物模型。通过 Western blot 和免疫荧光染色测量 TFEB 和自噬必需基因的表达。在 SAH 后 24 小时评估 SAH 分级、脑水含量和神经行为功能。通过 TUNEL 染色和 Fluoro Jade B 染色评估皮质神经元凋亡。SAH 大鼠 TFEB 下调,过表达 TFEB 可减轻脑水肿并改善 SAH 大鼠的神经功能缺损。此外,SAH 诱导的神经元凋亡被 TFEB 过表达所抑制。此外,TFEB 过表达可促进 SAH 后的自噬。TFEB 过表达通过促进自噬来抑制 SAH 后神经元凋亡、脑水肿和神经功能缺损。