Dr. Linda Phillips investigates the interaction between excessive neuroexcitation and neuronal deafferentation following traumatic brain injury (TBI), determining how this interaction affects both the ensuing pathology and synaptic recovery mechanisms. When these two insults are combined there is profound enhancement of neuropathology, including persistent cognitive deficits and maladaptive recovery of brain circuitry, both hallmarks of human TBI. From additional studies, it is also clear that pharmacological manipulation of NMDA and dopaminergic receptors can ameliorate injury-induced deficits in this model. Current studies from Dr. Phillips' laboratory show that major contributors to the morbidity and abnormal synaptic plasticity include cytoskeletal proteins, growth factors, extracellular matrix molecules and oxidative enzymes, as well as molecules associated with abnormal synaptic excitability. Based upon these findings, a combination of behavioral, structural, molecular and physiological analyses are being used to explore three cellular mechanisms which may regulate synaptic recovery after TBI: 1.) growth guidance by extracellular matrix molecules, 2.) sensitivity of mitochondrial metabolism and 3.) dopamine modulation of excitability. Working with Drs. Bullock Povlishock, TBI mitochondrial dysfunction is assessed using in vivo physiological parameters and ultrastructural markers of cell permeability or neuronal damage. Collaboration with Drs. Robert Hamm and Thomas Reeves permits analysis of synaptic function after TBI at both the behavioral and electrophysiological levels.

Dr. Ross Bullock, a neurosurgeon and an affiliate member of the Department, leads research efforts in both clinical and laboratory settings. Using innovative microdialysis monitoring of focal brain regions in head injured patients, coupled with measurements of oxygen and metabolites, Dr. Bullock's investigations have furthered the understanding of head injury and strategies for therapeutic intervention. In Dr. Bullock's laboratory, experimental models of subarachnoid hemorrhage and stroke have been developed and utilized to characterize the nature of pathophysiological mechanisms, as well as potential pharmacological protection.

Dr. Thomas Reeves, an affiliate member of the Department, specializes in the electrophysiological characterization of post-TBI pathophysiology. Recent experimental results suggest that mechanisms underlying neuroplasticity are particularly susceptible to TBI; for example, long-term potentiation (LTP) is impaired following TBI. Detailed analyses of these electrophysiological recordings indicates that injury does not uniformly affect the whole neuron, but rather specific subcellular compartments (e.g., dendrites vs. terminals) are differentially impacted. In collaboration with other faculty in the Neurotrauma Group, these functional measurements are integrated with diverse molecular, biochemical, and morphological outcome measures.

Dr. Richard Costanzo, an affiliate faculty in the Department of Physiology, focuses on the capacity of the olfactory system for continued neurogenesis and replacement of degenerating neurons. Recent findings have shown that the newly replaced neurons are capable of reestablishing functional connections with normal target cells as well as cells in other parts of the brain. Using anatomical, molecular, electrophysiological, and behavioral techniques, Dr. Costanzo's group is investigating the survival characteristics of olfactory stem cells when transplanted into different regions of the brain.