Epilepsy is a common brain disorder, repeated seizures of epilepsy may lead to a series of brain pathological changes such as neuronal or glial damage. However, whether circular RNAs are involved in neuronal injury during epilepsy is not fully understood. Here, we screened circIgf1r in the status epilepticus model through circRNA sequencing, and found that it was upregulated after the status epilepticus model through QPCR analysis. Astrocytes polarizing toward neurotoxic A1 phenotype and neurons loss were observed after status epilepticus. Through injecting circIgf1r siRNA into the lateral ventricle, it was found that knocking down circIgf1r in vivo would induce the polarization of astrocytes to phenotype A2 and reduce neuronal loss. The results in vitro further confirmed that inhibiting the expression of circIgf1r in astrocytes could protect neurons by converting reactive astrocytes from A1 to the protective A2. In addition, knocking down circIgf1r in astrocytes could functionally promote astrocyte autophagy and relieve the destruction of 4-AP-induced autophagy flux. In terms of mechanism, circIgf1r promoted the polarization of astrocytes to phenotype A1 by inhibiting autophagy. Taken together, our results reveal circIgf1r may serve as a potential target for the prevention and treatment of neuron damage after epilepsy.

中文翻译：

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circIgf1r的沉默通过调节癫痫期间的星形胶质细胞极化在神经元损伤中起保护作用

癫痫是一种常见的脑部疾病，癫痫的反复发作可能导致神经元或神经胶质损伤等一系列脑部病理变化。然而，环状 RNA 是否参与癫痫期间的神经元损伤尚不完全清楚。在这里，我们通过circRNA测序筛选了癫痫持续状态模型中的circIgf1r，通过QPCR分析发现它在癫痫持续状态模型后上调。在癫痫持续状态后观察到星形胶质细胞向神经毒性 A1 表型极化和神经元丢失。通过向侧脑室注射circIgf1r siRNA，发现在体内敲低circIgf1r会诱导星形胶质细胞极化为A2表型并减少神经元丢失。体外结果进一步证实，抑制星形胶质细胞中circIgf1r的表达可以通过将反应性星形胶质细胞从A1转化为保护性A2来保护神经元。此外，敲低星形胶质细胞中的 circIgf1r 可以在功能上促进星形胶质细胞自噬并减轻 4-AP 诱导的自噬通量的破坏。作用机制上，circIgf1r通过抑制自噬促进星形胶质细胞向A1表型极化。综上所述，我们的结果表明，circIgf1r 可能是预防和治疗癫痫后神经元损伤的潜在靶点。circIgf1r 通过抑制自噬促进星形胶质细胞极化为 A1 表型。综上所述，我们的结果表明，circIgf1r 可能是预防和治疗癫痫后神经元损伤的潜在靶点。circIgf1r 通过抑制自噬促进星形胶质细胞极化为 A1 表型。综上所述，我们的结果表明，circIgf1r 可能是预防和治疗癫痫后神经元损伤的潜在靶点。