Hippocampal injury and learning deficits following non-convulsive status epilepticus in periadolescent rats

• Published in: Epilepsy & behavior 2021-12, Vol.125, p.108415-108415, Article 108415
• Main Authors: Asdikian, Rita, Hajjar, Helene, Alturk, Sana, Asdikian, Jean-Pierre, Jaafar, Fatima, Salah, Houssein, Mrad, Yara, Issa, Farah, Almardini, Michel, Nourelddine, Fatima, Abdel Rassoul, Ronza, Al-Koussa, Houssam, Obeid, Makram
• Format: Article
• Language: English
• Subjects: Adolescent; Animals; Cognition; Hippocampus; Kainic Acid - toxicity; Neurons; Non-convulsive status epilepticus; Rats; Seizures; Status Epilepticus - chemically induced; Status Epilepticus - complications; Two-way active avoidance
• ISSN: 1525-5050; 1525-5069
• DOI: 10.1016/j.yebeh.2021.108415

•Subconvulsive kainate doses electroclinically reproduce non-convulsive status epilepticus (NCSE).•Non-convulsive status epilepticus results in hippocampal astrocytosis and learning deficits in periadolescent rats.•Non-convulsive status epilepticus recurrence alters hippocampal synaptophysin levels and potentiates learning deficits. The effects of non-convulsive status epilepticus (NCSE) on the developing brain remain largely elusive. Here we investigated potential hippocampal injury and learning deficits following one or two episodes of NCSE in periadolescent rats. Non-convulsive status epilepticus was induced with subconvulsive doses of intrahippocampal kainic acid (KA) under continuous EEG monitoring in postnatal day 43 (P43) rats. The RKA group (repeated KA) received intrahippocampal KA at P43 and P44, the SKA group (single KA injection) received KA at P43 and an intrahippocampal saline injection at P44. Controls were sham-treated with saline. The modified two-way active avoidance (MAAV) test was conducted between P45 and P52 to assess learning of context-cued and tone-signaled electrical foot-shock avoidance. Histological analyses were performed at P52 to assess hippocampal neuronal densities, as well as potential reactive astrocytosis and synaptic dysfunction with GFAP (glial fibrillary acidic protein) and synaptophysin (Syp) staining, respectively. Kainic acid injections resulted in electroclinical seizures characterized by behavioral arrest, oromotor automatisms and salivation, without tonic-clonic activity. Compared to controls, both the SKA and RKA groups had lower rates of tone-signaled shock avoidance (p  0.05), but the RKA group had learning deficits (p