Epilepsy is a chronic neurological disorder often associated with recurrent seizures. A growing body of evidence suggests that seizures cause structural and functional alterations of the brain. It is reported that behavioral abnormalities frequently occur in patients with epilepsy and experimental epilepsy models. However, the precise pathological mechanisms associated with these epilepsy comorbidities remain largely unknown. Neurogenesis persists throughout life in the hippocampal dentate gyrus (DG) to maintain proper brain function. However, aberrant neurogenesis usually generates abnormal neural circuits and consequently causes neuronal dysfunction. Neuroinflammatory responses are well known to affect neurogenesis and lead to aberrant reorganization of neural networks in the hippocampal DG. Here, in this study, we observed a significant increase in neuroinflammation and in the proliferation and survival of newborn granular cells in the hippocampus of pilocarpine-induced status epilepticus (SE) mice. More importantly, these proliferating and surviving newborn granular cells are largely ectopically located in the hippocampal DG hilus region. Our behavior test demonstrated that SE mice displayed severe aggressive behavior. Pharmacological inhibition of neuroinflammation, however, suppressed the ectopic neurogenesis and countered the enhanced aggressive behavior in SE mice, indicating that seizure-induced neuroinflammation may contribute to ectopic neurogenesis and aggressive behavior in SE mice. These findings establish a key role for neuroinflammation in seizure-induced aberrant neurogenesis and aggressive behavior. Suppressing neuroinflammation in the epileptic brain may reduce ectopic neurogenesis and effectively block the pathophysiological process that leads to aggressive behavior in TLE mice.

中文翻译：

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癫痫发作引起的神经炎症在毛果芸香碱引起的癫痫持续状态小鼠中促成异位神经发生和侵袭行为。

癫痫病是一种慢性神经系统疾病，通常与反复发作有关。越来越多的证据表明，癫痫发作会导致大脑的结构和功能改变。据报道，在癫痫和实验性癫痫模型患者中经常发生行为异常。然而，与这些癫痫合并症相关的确切病理机制仍不清楚。神经发生在整个海马齿状回（DG）中持续存在，以维持适当的脑功能。然而，异常的神经发生通常产生异常的神经回路，并因此引起神经元功能障碍。众所周知，神经炎症反应会影响神经发生并导致海马DG神经网络异常重组。在这里，在这项研究中 我们观察到毛发芸香碱引起的癫痫持续状态（SE）小鼠海马神经炎症以及新生颗粒细胞的增殖和存活显着增加。更重要的是，这些增殖和存活的新生颗粒细胞很大程度上异位位于海马DG hilus区。我们的行为测试表明SE小鼠表现出严重的攻击行为。然而，对神经炎症的药理学抑制作用抑制了SE小鼠的异位神经发生并抵消了其增强的攻击行为，这表明癫痫诱发的神经炎症可能有助于SE小鼠的异位神经发生和攻击行为。这些发现确立了神经炎在癫痫发作诱导的异常神经发生和攻击行为中的关键作用。