Date Available
5-6-2017
Year of Publication
2016
Document Type
Doctoral Dissertation
Degree Name
Doctor of Philosophy (PhD)
College
Medicine
Department/School/Program
Physiology
Advisor
Dr. Bret N. Smith
Abstract
Post-traumatic epilepsy is a common outcome of severe traumatic brain injury (TBI). The development of spontaneous seizures after traumatic brain injury generally follows a latent period of little to no symptoms. The series of events occurring in this latent period are not well understood. Additionally, there is no current treatment to prevent the development of epilepsy after TBI (i.e. antiepileptogenics). One cell signaling pathway activated in models of TBI and in models of epilepsy is the mammalian target of rapamycin (mTOR). mTOR activity is sustained for weeks after the initial insult in models of TBI, and the inhibition of mTOR using rapamycin has shown promising pre-clinical outcomes in rodent models. This makes rapamycin an ideal therapeutic to test various outcomes associated with epileptogenesis after TBI. The results from this study suggest that rapamycin treatment after controlled cortical impact reduces aberrant axonal sprouting of ipsilateral dentate granule cells, prevents increased neurogenesis in the subgranular zone, and differentially alters phasic and tonic inhibition in dentate granule cells. However, rapamycin treatment did not prevent all forms of axon sprouting in the dentate gyrus or cell loss in selected regions of the hippocampus. Collectively these results support a role of mTOR activity in both excitatory and inhibitory plasticity in the mouse dentate gyrus after TBI.
Digital Object Identifier (DOI)
http://dx.doi.org/10.13023/ETD.2016.182
Recommended Citation
Butler, Corwin R., "Effects of Mammalian Target of Rapamycin Inhibition on Circuitry Changes in the Dentate Gyrus of Mice after Focal Brain Injury" (2016). Theses and Dissertations--Physiology. 27.
https://uknowledge.uky.edu/physiology_etds/27
