ATG5-induced autophagy is triggered in the early stages after SAH, which plays a vital role in subarachnoid hemorrhage (SAH). Acyl-CoA synthetase short-chain family 2 (ACSS2) is not just involved in energy metabolism but also binds to TEFB to form a complex translocated to related autophagy genes to regulate the expression of autophagy-related genes. However, the contribution of ACSS2 to the activation of autophagy in early brain injury (EBI) after SAH has barely been discussed. The purpose of this study was to investigate the alterations of ACSS2 and its neuroprotective effects following SAH. We first evaluated the expression of ACSS2 at different time points (6, 12, 24, and 72 h after SAH) in vivo and primary cortical neurons stimulated by oxyhemoglobin (OxyHb). Subsequently, adeno-associated virus and lentivirus were used to regulate ACSS2 expression to investigate the effect of ACSS2 after SAH. The results showed that the ACSS2 level decreased significantly in the early stages of SAH and was minimized at 24 h post-SAH. After artificial intervention to overexpress ACSS2, ATG5-induced autophagy was further enhanced in EBI after SAH, and neuronal apoptosis was alleviated to protect brain injury. In addition, brain edema and neurological function scores were improved. These results suggest that ACSS2 plays an important role in the neuroprotection against EBI after SAH by increasing ATG5-induce autophagy and inhibiting apoptosis.

ATG5 诱导的自噬在 SAH 后的早期阶段被触发，这在蛛网膜下腔出血 (SAH) 中起着至关重要的作用。酰基辅酶A合成酶短链家族2（ACSS2）不仅参与能量代谢，还与TEFB结合形成复合物易位至相关自噬基因，调节自噬相关基因的表达。然而，ACSS2 对 SAH 后早期脑损伤 (EBI) 自噬激活的贡献几乎没有被讨论过。本研究的目的是研究 SAH 后 ACSS2 的改变及其神经保护作用。我们首先评估了 ACSS2 在体内不同时间点（SAH 后 6、12、24 和 72 小时）和氧合血红蛋白 (OxyHb) 刺激的原代皮层神经元的表达。随后，腺相关病毒和慢病毒用于调节 ACSS2 的表达以研究 ACSS2 在 SAH 后的作用。结果表明 ACSS2 水平在 SAH 早期显着下降，并在 SAH 后 24 h 降至最低。人工干预过表达ACSS2后，SAH后EBI中ATG5诱导的自噬进一步增强，神经元凋亡得到缓解，从而保护脑损伤。此外，脑水肿和神经功能评分也有所改善。这些结果表明 ACSS2 通过增加 ATG5 诱导自噬和抑制细胞凋亡在 SAH 后针对 EBI 的神经保护中起重要作用。人工干预过表达ACSS2后，SAH后EBI中ATG5诱导的自噬进一步增强，神经元凋亡得到缓解，从而保护脑损伤。此外，脑水肿和神经功能评分也有所改善。这些结果表明 ACSS2 通过增加 ATG5 诱导自噬和抑制细胞凋亡在 SAH 后针对 EBI 的神经保护中起重要作用。人工干预过表达ACSS2后，SAH后EBI中ATG5诱导的自噬进一步增强，神经元凋亡得到缓解，从而保护脑损伤。此外，脑水肿和神经功能评分也有所改善。这些结果表明 ACSS2 通过增加 ATG5 诱导自噬和抑制细胞凋亡在 SAH 后针对 EBI 的神经保护中起重要作用。