eprintid: 10076564 rev_number: 20 eprint_status: archive userid: 608 dir: disk0/10/07/65/64 datestamp: 2019-06-25 14:24:01 lastmod: 2021-10-09 22:43:10 status_changed: 2019-06-25 14:24:01 type: article metadata_visibility: show creators_name: Noè, F creators_name: Cattalini, A creators_name: Vila Verde, D creators_name: Alessi, C creators_name: Colciaghi, F creators_name: Figini, M creators_name: Zucca, I creators_name: de Curtis, M title: Epileptiform activity contralateral to unilateral hippocampal sclerosis does not cause the expression of brain damage markers ispublished: pub divisions: UCL divisions: B04 divisions: C05 divisions: F48 keywords: brain damage, epilepsy, focal seizures, nonconvulsive status epilepticus note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. abstract: OBJECTIVE: Patients with epilepsy often ask if recurrent seizures harm their brain and aggravate their epileptic condition. This crucial question has not been specifically addressed by dedicated experiments. We analyze here if intense bilateral seizure activity induced by local injection of kainic acid (KA) in the right hippocampus produces brain damage in the left hippocampus. METHODS: Adult guinea pigs were bilaterally implanted with hippocampal electrodes for continuous video-electroencephalography (EEG) monitoring. Unilateral injection of 1 μg KA in the dorsal CA1 area induced nonconvulsive status epilepticus (ncSE) characterized by bilateral hippocampal seizure discharges. This treatment resulted in selective unilateral sclerosis of the KA-injected hippocampus. Three days after KA injection, the animals were killed, and the brains were submitted to ex vivo magnetic resonance imaging (MRI) and were processed for immunohistochemical analysis. RESULTS: During ncSE, epileptiform activity was recorded for 27.6 ± 19.1 hours in both the KA-injected and contralateral hippocampi. Enhanced T1-weighted MR signal due to gadolinium deposition, mean diffusivity reduction, neuronal loss, gliosis, and blood-brain barrier permeability changes was observed exclusively in the KA-injected hippocampus. Despite the presence of a clear unilateral hippocampal sclerosis at the site of KA injection, no structural alterations were detected by MR and immunostaining analysis performed in the hippocampus contralateral to KA injection 3 days and 2 months after ncSE induction. Fluoro-Jade and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining at the same time points confirmed the absence of degenerating cells in the hippocampi contralateral to KA injection. SIGNIFICANCE: We demonstrate that intense epileptiform activity during ncSE does not cause obvious brain damage in the hippocampus contralateral to unilateral hippocampal KA injection. These findings argue against the hypothesis that epileptiform activity per se contributes to focal brain injury in previously undamaged cortical regions. date: 2019-06 date_type: published official_url: https://doi.org/10.1111/epi.15611 oa_status: green full_text_type: other language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1660464 doi: 10.1111/epi.15611 language_elements: English lyricists_name: Figini, Matteo lyricists_id: MMFIG52 actors_name: Figini, Matteo actors_id: MMFIG52 actors_role: owner full_text_status: public publication: Epilepsia volume: 60 number: 6 pagerange: 1184-1199 event_location: United States issn: 1528-1167 citation: Noè, F; Cattalini, A; Vila Verde, D; Alessi, C; Colciaghi, F; Figini, M; Zucca, I; Noè, F; Cattalini, A; Vila Verde, D; Alessi, C; Colciaghi, F; Figini, M; Zucca, I; de Curtis, M; - view fewer <#> (2019) Epileptiform activity contralateral to unilateral hippocampal sclerosis does not cause the expression of brain damage markers. Epilepsia , 60 (6) pp. 1184-1199. 10.1111/epi.15611 <https://doi.org/10.1111/epi.15611>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10076564/3/Figini_Epileptiform%20activity%20contralateral%20to%20unilateral%20hippocampal%20sclerosis%20does%20not%20cause%20the%20expression%20of%20brain%20damage%20markers_AAM.pdf