Knockout of Transient Receptor Potential Melastatin 4 Channel Mitigates Cerebral Edema and Neuronal Injury After Status Epilepticus in Mice
Knockout of Transient Receptor Potential Melastatin 4 Channel Mitigates Cerebral Edema and Neuronal Injury After Status Epilepticus in Mice
复制标题
敲除瞬时受体电位 Melastatin 4 通道可减轻小鼠癫痫持续状态后的脑水肿和神经元损伤
DOI：
10.1093/jnen/nlaa134
复制
发表时间：
2020-12-01
影响因子：
3.2
通讯作者：
Pan, Suyue
中科院分区：
文献类型：
--
作者：
Chen, Xing;Liu, Kewei;Pan, Suyue
本研究旨在评估瞬时受体电位melastatin 4（TRPM 4）基因敲除是否可以减轻癫痫持续状态（SE）小鼠模型的脑水肿并改善神经功能结局。在SE发作后2.5小时，终止具有由锂（10 mEq/kg）和毛果芸香碱（30-40 mg/kg）诱导的行为癫痫发作的野生型（WT）（n = 61）和Trpm 4（-/-）小鼠（n = 61）。SE后，观察28只WT-SE和27只Trpm 4（-/-）-SE小鼠28天，并评估其存活率和认知功能;其他小鼠在24小时、72小时或7天后处死，并评估脑水肿和组织学损伤。与WT-SE小鼠相比，Trpm 4（-/-）-SE小鼠在SE后28天的死亡率和认知缺陷显著改善。通过磁共振成像评估，Trpm 4（-/-）-SE小鼠也显示出较少的含水量和脑水肿，并且SE后血脑屏障破坏减少。此外，Trpm 4缺陷显着减轻海马和梨状皮质中的神经元丢失、细胞坏死和凋亡，并减轻星形胶质细胞增多和小胶质细胞增生。总之，这项研究表明，Trmp 4可能是改善SE后结局的新靶点。
This study aimed to evaluate whether the knockout of transient receptor potential melastatin 4 (TRPM4) could reduce cerebral edema and improve neurologic outcome in a mouse model of status epilepticus (SE). Wild-type (WT) (n = 61) and Trpm4(-/-) mice (n = 61) with behavioral seizures induced by lithium (10 mEq/kg) and pilocarpine (30-40 mg/kg) were terminated 2.5 hours after the onset of SE. After SE, 28 WT-SE and 27 Trpm4(-/-)-SE mice were observed for 28 days and assessed for survival and cognitive function; the others were killed after 24 hours, 72 hours, or 7 days, and evaluated for cerebral edema and histological injury. In comparison to WT-SE mice, the mortality and cognitive deficit for Trpm4(-/-)-SE mice following SE after 28 days were significantly ameliorated. Trpm4(-/-)-SE mice also showed less water content and cerebral edema assessed by magnetic resonance imaging, and decreased blood-brain barrier breakdown after SE. Moreover, Trpm4 deficiency significantly mitigated neuronal loss, cellular necrosis and apoptosis in the hippocampus and piriform cortex and mitigated astrocytosis and microgliosis. In conclusion, this study suggests that Trmp4 may represent a new target for improving outcomes after SE.