Show simple item record

dc.contributor.advisorSimeone, Timothy A.en_US
dc.contributor.authorRanade, Nirupamaen_US
dc.date.accessioned2013-08-29T18:10:30Z
dc.date.available2015-06-01T08:40:09Z
dc.date.issued2013-08-22en_US
dc.identifier.urihttp://hdl.handle.net/10504/45566
dc.description.abstractPeroxisome proliferator activated receptor gamma (PPARγ) is a ligand-modulated transcription factor belonging to the nuclear receptor superfamily. PPARγ regulates genes involved in adipocyte differentiation, insulin homeostasis, neuroprotection and anti-inflammation. As such, PPARγ is under consideration as therapy for ischemic stroke, Alzheimer's disease, Parkinson's disease, multiple sclerosis and traumatic brain injury. Previous in vivo experiments using acute seizure models and preliminary studies in our laboratory using chronic seizure models suggest PPARγ agonists have anticonvulsant efficacy. These results, however, need to be replicated at a more concentrated level to understand tissue-specific effects. Thus, we performed extracellular electrophysiological experiments with a PPARγ agonist (pioglitazone) and an antagonist (GW 9662) to test their efficacy in an in vitro model of seizure using high potassium. We observed that pioglitazone delayed the latency to seizure-like events (SLE) onset and decreased the intraSLE frequency by increasing the duration of each SLE in WT slices. It also decreased the severity of SLEs, as indicated by a significant decrease in the linelength of the WT slices. GW 9662 reversed all of pioglitazone effects except the delayed SLE onset. Furthermore, pioglitazone failed to reduce high potassium-induced hyperexcitability in slices from PPARγ neuronal knock out (NKO) mice. These results support the hypothesis that activation of PPARγ via pioglitazone attenuates various parameters of high potassium-induced hyperexcitability. The effectiveness in this in-vitro acute hippocampal slice high potassium model of SLE affords a reduced system to study the anticonvulsant mechanism of pioglitazone via PPARγ activation.en_US
dc.language.isoen_USen_US
dc.publisherCreighton Universityen_US
dc.rightsCopyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.en_US
dc.subject.meshAnticonvulsants--therapeutic useen_US
dc.subject.meshPPAR gamma--drug therapyen_US
dc.subject.meshSeizures--drug therapyen_US
dc.titleAnticonvulsant effects of PPAR-gamma activation in an in vitro model of seizureen_US
dc.typeThesis
dc.rights.holderNirupama Ranadeen_US
dc.publisher.locationOmaha, Nebraskaen_US
dc.description.noteProQuest Traditional Publishing Optionen_US
dc.description.pagesix, 98 pagesen_US
dc.contributor.cuauthorRanade, Nirupamaen_US
dc.embargo.terms2015-06-01
dc.degree.levelMS (Master of Science)en_US
dc.degree.disciplinePharmaceutical Science (graduate program)en_US
dc.degree.nameM.S. in Pharmaceutical Sciencesen_US
dc.degree.grantorGraduate Schoolen_US
dc.degree.committeeMurray, Thomas F.en_US
dc.degree.committeeDravid, Shashank M.en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record