Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.

Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some o...

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Autores principales:	Amanda E Hernan, Abigail Alexander, Pierre-Pascal Lenck-Santini, Rod C Scott, Gregory L Holmes
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/21a6ab10ae8f45cf86e0e904ce338240
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spelling	oai:doaj.org-article:21a6ab10ae8f45cf86e0e904ce3382402021-11-18T08:31:16ZAttention deficit associated with early life interictal spikes in a rat model is improved with ACTH.1932-620310.1371/journal.pone.0089812https://doaj.org/article/21a6ab10ae8f45cf86e0e904ce3382402014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24587054/?tool=EBIhttps://doaj.org/toc/1932-6203Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These hypotheses are difficult to address due to the previous lack of an appropriate animal model. To this end, we have recently developed a rat model to test the role of frequent focal epileptiform activity in the prefrontal cortex. Using microinjections of a GABA(A) antagonist (bicuculline methiodine) delivered multiple times per day from postnatal day (p) 21 to p25, we showed that rat pups experiencing frequent, focal, recurrent epileptiform activity in the form of interictal spikes during neurodevelopment have significant long-term deficits in attention and sociability that persist into adulthood. To determine if treatment with ACTH, a drug widely used to treat early-life seizures, altered outcome we administered ACTH once per day subcutaneously during the time of the induced interictal spike activity. We show a modest amelioration of the attention deficit seen in animals with a history of early life interictal spikes with ACTH, in the absence of alteration of interictal spike activity. These results suggest that pharmacological intervention that is not targeted to the interictal spike activity is worthy of future study as it may be beneficial for preventing or ameliorating adverse cognitive outcomes.Amanda E HernanAbigail AlexanderPierre-Pascal Lenck-SantiniRod C ScottGregory L HolmesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 2, p e89812 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amanda E Hernan Abigail Alexander Pierre-Pascal Lenck-Santini Rod C Scott Gregory L Holmes Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.
description	Children with epilepsy often present with pervasive cognitive and behavioral comorbidities including working memory impairments, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder. These non-seizure characteristics are severely detrimental to overall quality of life. Some of these children, particularly those with epilepsies classified as Landau-Kleffner Syndrome or continuous spike and wave during sleep, have infrequent seizure activity but frequent focal epileptiform activity. This frequent epileptiform activity is thought to be detrimental to cognitive development; however, it is also possible that these IIS events initiate pathophysiological pathways in the developing brain that may be independently associated with cognitive deficits. These hypotheses are difficult to address due to the previous lack of an appropriate animal model. To this end, we have recently developed a rat model to test the role of frequent focal epileptiform activity in the prefrontal cortex. Using microinjections of a GABA(A) antagonist (bicuculline methiodine) delivered multiple times per day from postnatal day (p) 21 to p25, we showed that rat pups experiencing frequent, focal, recurrent epileptiform activity in the form of interictal spikes during neurodevelopment have significant long-term deficits in attention and sociability that persist into adulthood. To determine if treatment with ACTH, a drug widely used to treat early-life seizures, altered outcome we administered ACTH once per day subcutaneously during the time of the induced interictal spike activity. We show a modest amelioration of the attention deficit seen in animals with a history of early life interictal spikes with ACTH, in the absence of alteration of interictal spike activity. These results suggest that pharmacological intervention that is not targeted to the interictal spike activity is worthy of future study as it may be beneficial for preventing or ameliorating adverse cognitive outcomes.
format	article
author	Amanda E Hernan Abigail Alexander Pierre-Pascal Lenck-Santini Rod C Scott Gregory L Holmes
author_facet	Amanda E Hernan Abigail Alexander Pierre-Pascal Lenck-Santini Rod C Scott Gregory L Holmes
author_sort	Amanda E Hernan
title	Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.
title_short	Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.
title_full	Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.
title_fullStr	Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.
title_full_unstemmed	Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.
title_sort	attention deficit associated with early life interictal spikes in a rat model is improved with acth.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/21a6ab10ae8f45cf86e0e904ce338240
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Attention deficit associated with early life interictal spikes in a rat model is improved with ACTH.

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