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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 (<jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content>) in the right hippocampus produces brain damage in the left hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Adult guinea pigs were bilaterally implanted with hippocampal electrodes for continuous video\u2014electroencephalography (EEG) monitoring. Unilateral injection of 1\u00a0\u03bcg <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content> in the dorsal <jats:styled-content style=\"fixed-case\">CA<\/jats:styled-content>1 area induced nonconvulsive status epilepticus (nc<jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>) characterized by bilateral hippocampal seizure discharges. This treatment resulted in selective unilateral sclerosis of the <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content>\u2010injected hippocampus. Three days after <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content> injection, the animals were killed, and the brains were submitted to ex vivo magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>) and were processed for immunohistochemical analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During nc<jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content>, epileptiform activity was recorded for 27.6\u00a0\u00b1\u00a019.1\u00a0hours in both the <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content>\u2010injected and contralateral hippocampi. Enhanced T1\u2010weighted <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> signal due to gadolinium deposition, mean diffusivity reduction, neuronal loss, gliosis, and blood\u2013brain barrier permeability changes was observed exclusively in the <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content>\u2010injected hippocampus. Despite the presence of a clear unilateral hippocampal sclerosis at the site of <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content> injection, no structural alterations were detected by <jats:styled-content style=\"fixed-case\">MR<\/jats:styled-content> and immunostaining analysis performed in the hippocampus contralateral to <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content> injection 3\u00a0days and 2\u00a0months after nc<jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content> induction. Fluoro\u2010Jade 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 <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content> injection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>We demonstrate that intense epileptiform activity during nc<jats:styled-content style=\"fixed-case\">SE<\/jats:styled-content> does not cause obvious brain damage in the hippocampus contralateral to unilateral hippocampal <jats:styled-content style=\"fixed-case\">KA<\/jats:styled-content> injection. These findings argue against the hypothesis that epileptiform activity per se contributes to focal brain injury\u00a0in previously undamaged cortical regions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.15611","type":"journal-article","created":{"date-parts":[[2019,5,21]],"date-time":"2019-05-21T08:50:57Z","timestamp":1558428657000},"page":"1184-1199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Epileptiform activity contralateral to unilateral hippocampal sclerosis does not cause the expression of brain damage markers"],"prefix":"10.1111","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0019-1615","authenticated-orcid":false,"given":"Francesco","family":"No\u00e8","sequence":"first","affiliation":[{"name":"Epilepsy Unit Fondazione IRCCS Istituto Neurologico Carlo Besta Milan 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