Status epilepticus (SE) during developmental periods can cause short- and long-term consequences to the brain. Brain damage induced by SE is associated to NMDA receptors (NMDAR)-mediated excitotoxicity. This study aimed to investigate whether blockade of GluN2B-containing NMDAR is neuroprotective against SE-induced neurodegeneration and neuroinflammation in young rats. Forty-eight Wistar rats (16 days of life) were injected with pilocarpine (60 mg/kg; i.p.) 12-18 h after LiCl (3 mEq/kg; i.p.). Fifteen minutes after pilocarpine administration, animals received i.p. injections of saline solution (0.9% NaCl; SE + SAL group), ketamine (a non-selective and noncompetitive NMDAR antagonist; 25 mg/kg; SE + KET), CI-1041 (a GluN2B-containing NMDAR antagonist; 10 mg/kg; SE + CI group) or CP-101,606 (a NMDAR antagonist with great selectivity for NMDAR composed by GluN1/GluN2B diheteromers; 10 mg/kg; SE + CP group). Seven days after SE, brains were removed for Fluoro-Jade C staining and Iba1/ED1 immunolabeling. GluN2B-containing NMDAR blockade by CI-1041 or CP-101,606 did not terminate LiCl-pilocarpine-induced seizures. SE + SAL group presented intense neurodegeneration and Iba1+/ED1+ double-labeling in hippocampus (CA1 and dentate gyrus; DG) and amygdala (MePV nucleus). Administration of CP-101,606 did not alter this pattern. However, GluN2B-containing NMDAR blockade by CI-1041 reduced neurodegeneration and Iba1+/ED1+ double-labeling in hippocampus and amygdala similar to the reduction observed for SE + KET group. Our results indicate that GluN2B-containing NMDAR are involved in SE-induced neurodegeneration and microglial recruitment and activation, and suggest that stopping epileptic activity is not a condition required to prevent short-term brain damage in young animals.

中文翻译：

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含有GluN2B的NMDA受体的阻滞减少了因早期生命状态癫痫引起的短期脑损伤。

发育期的癫痫持续状态（SE）可能对大脑造成短期和长期影响。SE诱发的脑损伤与NMDA受体（NMDAR）介导的兴奋性毒性有关。这项研究旨在调查含GluN2B的NMDAR是否对年轻大鼠SE诱导的神经退行性变和神经发炎具有神经保护作用。在LiCl（3 mEq / kg; ip）后12-18小时向48只Wistar大鼠（生命16天）注射毛果芸香碱（60 mg / kg; ip）。给予毛果芸香碱15分钟后，动物接受腹腔注射盐溶液（0.9％NaCl； SE + SAL组），氯胺酮（非选择性和非竞争性NMDAR拮抗剂； 25 mg / kg； SE + KET），CI-1041（a含GluN2B的NMDAR拮抗剂； 10 mg / kg； SE + CI组）或CP-101，606（由GluN1 / GluN2B二异聚体组成的对NMDAR具有极高选择性的NMDAR拮抗剂； 10 mg / kg； SE + CP组）。SE后7天，取出大脑进行Fluoro-Jade C染色和Iba1 / ED1免疫标记。CI-1041或CP-101,606对含GluN2B的NMDAR的阻断并没有终止LiCl-毛果芸香碱引起的癫痫发作。SE + SAL组在海马（CA1和齿状回； DG）和杏仁核（MePV核）中表现出强烈的神经变性和Iba1 + / ED1 +双重标记。CP-101,606的管理并未更改此模式。但是，CI-1041对含GluN2B的NMDAR的阻滞减少了海马和杏仁核中的神经变性和Iba1 + / ED1 +双重标记，与SE + KET组的减少相似。