Pharmacological and environmental approaches for neurobehavioral and histological recovery after experimental traumatic brain injury.
Dr. Kline is the Associate Director of Rehabilitation Research, Safar Center for Resuscitation Research.
Traumatic brain injury (TBI) affects 2 million people in the United States each year, making it one of the more prevalent and debilitating of all neurological disorders. Approximately 300,000 of the TBI cases are severe enough to warrant hospitalization, where 50,000 die. Of the 250,000 survivors, 100,000 endure long-term disabilities that require rigorous, lengthy, and costly medical and rehabilitative care. TBI is a serious and survivable medical problem with limited treatment options and therefore empirical research aimed at finding therapies that may benefit outcome and/or elucidate treatments that may be deleterious to the recovery process (e.g., antipsychotics) are urgently needed. To this end, my laboratory utilizes a clinically relevant rodent model of TBI to produce motor and cognitive deficits that are reminiscent of those seen in human patients (adults and pediatrics). Therapeutic strategies such as pharmacotherapies, environmental enrichment, and their combination are subsequently provided in an attempt to restore function and/or attenuate TBI-induced deficits. Recent therapeutic approaches in the laboratory include the utilization of moderate hypothermia, antioxidants, as well as DAergic, 5-HT1A receptor agonists, and AChE inhibitors. The long-term goals of the laboratory are to develop therapies that facilitate functional recovery after human TBI and to elucidate potential mechanisms for the observed effects. My laboratory is located in the Safar Center for Resuscitation Research (SCRR) where ample collaboration exists between brain experts from the Departments of Physical Medicine & Rehabilitation, Neurological Surgery, and Critical Care Medicine. This wealth of knowledge, which includes, but is not limited to, numerous behavioral assessments as well as a variety of molecular and immunocytochemistry techniques, is available to graduate students whose interests are consistent with the overall goals of the laboratory.
Hoffman, A.N., Cheng, J.P., Zafonte, R.D. and Kline, A.E. Administration of haloperidol and risperidone after neurobehavioral testing hinders the recovery of traumatic brain injury-induced deficits. Life Sci. 83:602-607, 2008.
Cheng, J.P., Hoffman, A.N., Zafonte, R.D. and Kline, A.E. A delayed and chronic treatment regimen with the 5-HT1A receptor agonist 8-OH-DPAT after cortical impact injury facilitates motor recovery and acquisition of spatial learning. Behav Brain Res. 194: 79-85, 2008.
Hoffman, A.N., Malena, R.R., Westergom, B.P., Luthra, P., Cheng, J.P., Aslam, H.A., Zafonte, R.D. and Kline, A.E. Environmental enrichment-mediated functional improvement after experimental traumatic brain injury is contingent on task-specific neurobehavioral experience. Neurosci Lett. 431: 226-230, 2008.
Kline, A.E., Wagner, A.K., Westergom, B.P., Malena, R.R., Zafonte, R.D., Olsen, A.S., Sozda, C.N., Luthra, P., Panda, M., Cheng, J.P. and Aslam, H.A. Acute treatment with the 5-HT(1A) receptor agonist 8-OH-DPAT and chronic environmental enrichment confer neurobehavioral benefit after experimental brain trauma. Behav Brain Res. 177: 186-194, 2007.
Kline, A.E., Massucci, J.L., Zafonte, R.D., Dixon, C.E., DeFeo, J.R. and Rogers, E.H. Differential effects of single versus multiple administrations of haloperidol and risperidone on functional outcome after experimental brain trauma. Crit Care Med. 35:919-924, 2007.
Kline, A.E., Massucci, J.L., Dixon, C.E., Zafonte, R.D. and Bolinger, B.D. The therapeutic efficacy conferred by the 5-HT(1A) receptor agonist 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) after experimental traumatic brain injury is not mediated by concomitant hypothermia. J Neurotrauma. 21: 175-185, 2004.