LAUSR

HighlightsGluN2B‐containing NMDAR blockage did not terminate status epilepticus.Ketamine and CI‐1041 treatments accelerated weight recovery after status epilepticus.Status epilepticus termination is not required for prevention of neuronal loss.GluN2B‐containing NMDAR are involved in status epilepticus‐induced brain damage.CP‐101,606 administration did not prevent status epilepticus‐induced neuronal death. Abstract 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.