Pathophysiology of traumatic brain injury. Excitotoxic cascades affecting cell survival and behavior. Development of therapeutic interventions for brain injury.

Dr. Lyeth's laboratory uses a variety of pharmacological, surgical, neuroanatomical, and behavioral methods to investigate the neural mechanisms involved in traumatic brain injury pathology. The ultimate goal of this research program is to develop novel clinical therapeutic strategies targeted at reducing the debilitating consequences of traumatic brain injury in patients. Pre-clinical testing of novel therapeutic strategies and compounds are routinely performed in this laboratory. Previous efforts have led to ongoing clinical trials evaluating hypothermia and glutamate receptor antagonists as therapeutic interventions for traumatic brain injury patients.

Dr. Lyeth's current work focuses on the following: 1) investigating astrocyte - neuronal interactions in brain injury pathophysiology; 2) examinig how certain neuropeptides can modulate glutamate excitotoxicity; 3) preclinincal testing of novel therapeutic agents for CNS injury.

Publications:

Zhang B, West EJ, Van KC, Gurkoff GG, Zhou, J, Zhang X-M, Kozikowski AP, Lyeth BG. HDAC inhibitor increases histone H3 acetylation and reduces microglia inflammatory response following traumatic brain injury in rats. Brain Research 1226:181-191, 2008.

Zhao X, Gorin FA, Berman, RF, Lyeth BG. Differential hippocampal protection when blocking intracellular sodium and calcium entry during traumatic brain injury in rats. J Neurotrauma 25(10):1195-1205, 2008.

Cox CD, West EJ, Liu MC, Wang, KKW, Hayes RL, Lyeth BG. Dicyclomine, an M1 muscarinic antagonist, reduces biomarker levels, but not neuronal degeneration, in fluid percussion brain injury. J Neurotrauma 25(11):1355-1365, 2008.

Folkerts MM, Parks EA, Dedman J, Kaetzel M, Lyeth BG, Berman RF. Phosphorylation of calcium calmodulin-dependent protein kinase II following lateral fluid percussion brain injury in rats. J Neurotrauma 24(4): 638-650, 2007.

Floyd, CL, Lyeth BG. Astroglia: Important Mediators of Traumatic Brain Injury. In: Neurotrauma: New Insights into Pathology and Treatment. Progress in Brain Research, 161. Eds. Weber J.T. & Mass A.I.R. Elsevier: Amsterdam, 2007.

Zhong C, Zhao X, Van KC, Bzdega T, Smyth A, Zhou J. Kozikowski AP, Jiang J, OConnor WT, Berman RF, Neale JH, Lyeth BG. NAAG peptidase inhibitor increases dialysate NAAG and reduces glutamate, aspartate and GABA levels in the dorsal hippocampus following fluid percussion injury in the rat. J Neurochemistry 97:1015-1025, 2006.

Zhong C, Zhao X, Sarva, J, Kozikowski A, Neale JH, Lyeth BG. NAAG Peptidase Inhibitor Reduces Acute Neuronal Degeneration and Astrocyte Damage Following Lateral Fluid Percussion TBI in Rats. J Neurotrauma 22(2): 266-276, 2005.

Floyd, CL, Gorin FA, Lyeth BG. Mechanical strain injury to cultured astrocytes increases intracellular sodium and reverses Na+/Ca++ exchange. GLIA 51(1):35-46, 2005.

Hallam TM, Floyd CL, Folkerts MM, Lee LL, Gong Q-Z, Lyeth BG, Muizelaar JP, Berman RF. Comparison of Behavioral Deficits and Acute Neuronal Degeneration in Rat Lateral Fluid Percussion and Weight Drop Brain Injury Models. J Neurotrauma 21(5):521-539, 2004.

Zhao X, Ahram A, Muizelaar JP, Berman RF, Lyeth BG. Early Loss Of Astrocytes After Experimental Traumatic Brain Injury. GLIA 44:140-152, 2003.

Rafiq A, Gong QZ, Lyeth BG, DeLorenzo RJ, Coulter DA. Induction of prolonged electrographic seizures in vitro has a defined threshold and is all or none: implications for diagnosis of status epilepticus. Epilepsia 44:1034-1041, 2003

Hu G., Lyeth BG, Zhao X, Mitchell JB, Watson JC. Robust neuroprotection by the stable nitroxide 3-CP during reperfusion in a rat model of transient focal ischemia. J Neurosurgery 98:393-396, 2003.

Floyd CL, Golden KM, Black RT, Hamm RJ, Lyeth BG. Craniectomy Position Affects Morris Water Maze Performance and Hippocampal Cell Loss Following Parasagittal Fluid Percussion. J Neurotrauma 19(3):303- 316, 2002.

Zwienenberg M, Gong Q-Z, Berman RF, Muizelaar JP, Lyeth BG, The effect of group II and III metabotropic glutamate receptor activation on neuronal injury in a rodent model of traumatic brain injury. Neurosurgery 48(5):1119-1126, 2001.

Jiang Z-W, Gong Q-Z, Di, X, Zhu J, Lyeth BG, Dicyclomine, an m1 muscarinic antagonist, reduces infarct volume in a rat subdural hematoma model. Brain Research 852:37-44, 2000.