The objective of our Neurotrauma Research Center at the University of Miami Miller School of Medicine is to carry out a program of integrated multidisciplinary experimental research into the mechanisms and therapies for traumatic brain injury (TBI). The ultimate goal is to identify factors resulting from TBI that may be amenable to specific therapeutic interventions in the acute, subacute and chronic stages. This current Program Project consists of investigative proposals directed at developing strategies and providing new data concerning recovery of function after TBI. These investigations are supported by Core facilities in the areas of animal physiology, neuropathology, molecular biology, electrophysiology, image processing and behavior. Established animal models including fluid-percussion (F-P) injury and cortical impact injury in rats and mice are utilized. Project 1 will examine the role of B-class ephrins and their respective receptors in the hippocampus following TBI. These studies will examine the role of ephrins and Eph receptors on astrocyte function and astrocyte-synaptic interactions. Project 2 will investigate molecular mechanisms of synaptic hyper-excitability and epileptic susceptibility after TBI. This project will test the hypothesis that activation of TrkB and ephrin B receptors plays a key role in posttraumatic seizure susceptibility. Project 3 will investigate the effects of injury severity on chronic circuit function and changes in synaptic plasticity after TBI. The use of an enriched environment (EE) as well as novel therapies and interventions to enhance behavioral and synaptic plasticity will be investigated. Finally, Project 4 will investigate the beneficial effects of transplantation of neuroprogenitor cells expressing a multi-neurotrophin. Studies will investigate underlying mechanisms for observed improvement and affects on synaptic plasticity. Potential detrimental side effects of this cell therapy will also be assessed including post-traumatic seizure potential and aberrant axonal sprouting. The Program Project is supported by an established group of scientists who provide the expertise necessary to conduct this multi-disciplinary program in TBI. Together, these experimental studies should enhance our understanding of the critical events associated with acute and more chronic brain trauma and help identify novel treatment strategies to promote neuroprotection, cellular replacement, remyelination and recovery of function in human TBI.

Public Health Relevance

Traumatic brain injury is a leading cause of death and disability in the United States. There are currently no therapies to protect and promote recovery in head injured patients. The present proposal will further investigate pathomechanisms and new therapies targeting cognitive dysfunction and posttraumatic seizures.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center (P50)
Project #
Application #
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Hicks, Ramona R
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Miami School of Medicine
Schools of Medicine
Coral Gables
United States
Zip Code
Blaya, Meghan O; Tsoulfas, Pantelis; Bramlett, Helen M et al. (2015) Neural progenitor cell transplantation promotes neuroprotection, enhances hippocampal neurogenesis, and improves cognitive outcomes after traumatic brain injury. Exp Neurol 264:67-81
Theus, M H; Ricard, J; Glass, S J et al. (2014) EphrinB3 blocks EphB3 dependence receptor functions to prevent cell death following traumatic brain injury. Cell Death Dis 5:e1207
Baumann, Gisela; Travieso, Lissette; Liebl, Daniel J et al. (2013) Pronounced hypoxia in the subventricular zone following traumatic brain injury and the neural stem/progenitor cell response. Exp Biol Med (Maywood) 238:830-41
Park, Yujung; Luo, Tianfei; Zhang, Fan et al. (2013) Downregulation of Src-kinase and glutamate-receptor phosphorylation after traumatic brain injury. J Cereb Blood Flow Metab 33:1642-9
Zhang, Fan; Guo, Ailan; Liu, Chunli et al. (2013) Phosphorylation and assembly of glutamate receptors after brain ischemia. Stroke 44:170-6
Atkins, Coleen M; Cepero, Maria L; Kang, Yuan et al. (2013) Effects of early rolipram treatment on histopathological outcome after controlled cortical impact injury in mice. Neurosci Lett 532:1-6
Sabirzhanova, Inna; Liu, Chunli; Zhao, Jingwei et al. (2013) Changes in the GEF-H1 pathways after traumatic brain injury. J Neurotrauma 30:1449-56
Truettner, Jessie S; Motti, Dario; Dietrich, W Dalton (2013) MicroRNA overexpression increases cortical neuronal vulnerability to injury. Brain Res 1533:122-30
Mawhinney, Lana J; de Rivero Vaccari, Juan Pablo; Alonso, Ofelia F et al. (2012) Isoflurane/nitrous oxide anesthesia induces increases in NMDA receptor subunit NR2B protein expression in the aged rat brain. Brain Res 1431:23-34
Bregy, Amade; Nixon, Ryan; Lotocki, George et al. (2012) Posttraumatic hypothermia increases doublecortin expressing neurons in the dentate gyrus after traumatic brain injury in the rat. Exp Neurol 233:821-8

Showing the most recent 10 out of 143 publications