The Role of Calcineurin in Dendritic Remodeling and Epileptogenesis in a Rat Model of Traumatic Brain Injury

...........................................................................................................................ix Introduction......................................................................................................................1 The Exciting but Risky Lives of Dendritic Spines..................................................1 Calcium and Dendritic Spine Plasticity.................................................................3 Post-Synaptic Mechanisms of Dendritic Spine Loss............................................10 Traumatic Brain Injury in Humans and Rodent Models.......................................21 Chapter I: Traumatic Brain Injury Causes an FK506-Sensitive Loss and an Overgrowth of Dendritic Spines in Rat Forebrain..............................................................................23 Introduction..........................................................................................................23 Materials and Methods........................................................................................25 Results.................................................................................................................29 Discussion............................................................................................................42 Chapter II: Mechanisms of Dendritic Spine Remodeling in a Rat Model of Traumatic Brain Injury....................................................................................................................75 Introduction..........................................................................................................75 Materials and Methods.........................................................................................76 a,b Text adapted from research manuscript in press, with written permission of publisher iv Results.................................................................................................................81 Discussion............................................................................................................97 Chapter III: Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in NonConvulsive Seizures in a Rat Model of Post-Traumatic Epilepsy................................123 Introduction........................................................................................................123 Materials and Methods.......................................................................................124 Results...............................................................................................................131 Discussion..........................................................................................................148 Discussion....................................................................................................................166 List of References.........................................................................................................171 Vita................................................................................................................................197