Glioma-induced peritumoral hyperexcitability in a pediatric glioma model

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dc.contributor.authorChaunsali, Lataen
dc.contributor.authorTewari, Bhanu P.en
dc.contributor.authorGallucci, Allisonen
dc.contributor.authorThompson, Emily G.en
dc.contributor.authorSavoia, Andrewen
dc.contributor.authorFeld, Noahen
dc.contributor.authorCampbell, Susan L.en
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.date.accessioned2021-09-03T12:48:38Zen
dc.date.available2021-09-03T12:48:38Zen
dc.date.issued2020-10-01en
dc.date.updated2021-09-03T12:48:34Zen
dc.description.abstractEpileptic seizures are among the most common presenting symptom in patients with glioma. The etiology of glioma-related seizures is complex and not completely understood. Studies using adult glioma patient tissue and adult glioma mouse models, show that neurons adjacent to the tumor mass, peritumoral neurons, are hyperexcitable and contribute to seizures. Although it is established that there are phenotypic and genotypic distinctions in gliomas from adult and pediatric patients, it is unknown whether these established differences in pediatric glioma biology and the microenvironment in which these glioma cells harbor, the developing brain, differentially impacts surrounding neurons. In the present study, we examine the effect of patient-derived pediatric glioma cells on the function of peritumoral neurons using two pediatric glioma models. Pediatric glioma cells were intracranially injected into the cerebrum of postnatal days 2 and 3 (p2/3) mouse pups for 7 days. Electrophysiological recordings showed that cortical layer 2/3 peritumoral neurons exhibited significant differences in their intrinsic properties compared to those of sham control neurons. Peritumoral neurons fired significantly more action potentials in response to smaller current injection and exhibited a depolarization block in response to higher current injection. The threshold for eliciting an action potential and pharmacologically induced epileptiform activity was lower in peritumoral neurons compared to sham. Our findings suggest that pediatric glioma cells increase excitability in the developing peritumoral neurons by exhibiting early onset of depolarization block, which was not previously observed in adult glioma peritumoral neurons.en
dc.description.versionPublished versionen
dc.format.extentPages e14567en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.14814/phy2.14567en
dc.identifier.eissn2051-817Xen
dc.identifier.issn2051-817Xen
dc.identifier.issue19en
dc.identifier.orcidCampbell, Susan [0000-0001-7775-8600]en
dc.identifier.pmid33026196en
dc.identifier.urihttp://hdl.handle.net/10919/104928en
dc.identifier.volume8en
dc.language.isoenen
dc.publisherWileyen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/33026196en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectdevelopmenten
dc.subjectgliomaen
dc.subjecthyperexcitabilityen
dc.subjectpediatricen
dc.subject0606 Physiologyen
dc.subject1103 Clinical Sciencesen
dc.subject1116 Medical Physiologyen
dc.subject.meshNeuronsen
dc.subject.meshTumor Cells, Cultureden
dc.subject.meshAnimalsen
dc.subject.meshHumansen
dc.subject.meshMiceen
dc.subject.meshMice, SCIDen
dc.subject.meshGliomaen
dc.subject.meshBrain Neoplasmsen
dc.subject.meshEpilepsyen
dc.subject.meshXenograft Model Antitumor Assaysen
dc.subject.meshAction Potentialsen
dc.subject.meshChilden
dc.subject.meshFemaleen
dc.subject.meshMaleen
dc.subject.meshTumor Microenvironmenten
dc.titleGlioma-induced peritumoral hyperexcitability in a pediatric glioma modelen
dc.title.serialPhysiological Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2020-08-10en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Animal and Poultry Sciencesen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen

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