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In recent years, it has become increasingly clear that <jats:italic>de novo<\/jats:italic> FncSE should be promptly treated to improve post\u2010status outcome. Whether seizure activity occurring during the course of the FncSE contributes to ensuing brain damage has not been demonstrated unequivocally and is here addressed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used continuous video\u2010EEG monitoring to characterise an acute experimental FncSE model induced by unilateral intrahippocampal injection of kainic acid (KA) in guinea pigs. Immunohistochemistry and mRNA expression analysis were utilised to detect and quantify brain injury, 3\u2010days and 1\u2010month after FncSE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seizure activity occurring during the course of FncSE involved both hippocampi equally. Neuronal loss, blood\u2010brain barrier permeability changes, gliosis and up\u2010regulation of inflammation, activity\u2010induced and astrocyte\u2010specific genes were observed in the KA\u2010injected hippocampus. Diazepam treatment reduced FncSE duration and KA\u2010induced neuropathological damage. In the contralateral hippocampus, transient and possibly reversible gliosis with increase of aquaporin\u20104 and Kir4.1 genes were observed 3\u00a0days post\u2010KA. No tissue injury and gene expression changes were found 1\u2010month after FncSE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In our model, focal seizures occurring during FncSE worsen ipsilateral KA\u2010induced tissue damage. FncSE only transiently activated glia in regions remote from KA\u2010injection, suggesting that seizure activity during FncSE without local pathogenic co\u2010factors does not promote long\u2010lasting detrimental changes in the brain. These findings demonstrate that in our experimental model, brain damage remains circumscribed to the area where the primary cause (KA) of the FncSE acts. Our study emphasises the need to use antiepileptic drugs to contain local damage induced by focal seizures that occur during FncSE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12693","type":"journal-article","created":{"date-parts":[[2021,1,15]],"date-time":"2021-01-15T01:22:04Z","timestamp":1610673724000},"page":"679-693","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Seizure activity and brain damage in a model of focal non\u2010convulsive <i>status epilepticus<\/i>"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-6552","authenticated-orcid":false,"given":"Diogo","family":"Vila Verde","sequence":"first","affiliation":[{"name":"Epilepsy Unit Fondazione Istituto Neurologico Carlo Besta  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Department of (Neuro) Pathology 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