? In the United States alone, 500,000 people suffer traumatic brain injury (TBI) annually, making TBI a leading cause of death and disability. With improved accident scene and emergency care, mortality rates have declined, with 2-4 million people surviving TBI. Patients and patient families chiefly complain about post-concussive syndrome, involving alterations in cognition, aggression, emotional stability, disinhibition, and personality. In fact, post-concussive syndrome resembles the symptoms of amygdala resection or degeneration. In light of these post-injury deficits, the proposed project initiates experimentation focused on whether a subset of symptoms that define post-concussion syndrome are mediated by damage to the amygdala in a clinically relevant lateral fluid percussion model of brain injury in the mouse. The central hypothesis is: experimental TBI damages the amygdala bilaterally.
Three aims test the hypothesis: (1) to demonstrate amygdala-dependent cognitive deficits using conditioned fear, (2) to quantify selective neuronal loss in the basolateral complex and central nucleus of the amygdala using design-based stereology, and (3) to evaluate and pharmacologically modulate functional circuitry and synaptic plasticity in the amygdala-hippocampal circuit using extracellular field recordings. The systems approach to investigate amygdala pathology after TBI, in terms of behavior, anatomy and function, can reveal mechanisms underlying post-concussion syndrome. This research effort may lead to novel treatments for the affective disorders in an otherwise healthy brain-injured population, in addition to post-traumatic stress disorder and psychosis. ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD049343-01A1
Application #
6837236
Study Section
Special Emphasis Panel (ZRG1-F01 (20))
Program Officer
Nitkin, Ralph M
Project Start
2004-09-20
Project End
2006-09-19
Budget Start
2004-09-20
Budget End
2005-09-19
Support Year
1
Fiscal Year
2004
Total Cost
$48,928
Indirect Cost
Name
Virginia Commonwealth University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Lifshitz, Jonathan; Witgen, Brent M; Grady, M Sean (2007) Acute cognitive impairment after lateral fluid percussion brain injury recovers by 1 month: evaluation by conditioned fear response. Behav Brain Res 177:347-57
Lifshitz, Jonathan; Kelley, Brian Joseph; Povlishock, John Theodore (2007) Perisomatic thalamic axotomy after diffuse traumatic brain injury is associated with atrophy rather than cell death. J Neuropathol Exp Neurol 66:218-29
Tran, Lorriann D; Lifshitz, Jonathan; Witgen, Brent M et al. (2006) Response of the contralateral hippocampus to lateral fluid percussion brain injury. J Neurotrauma 23:1330-42
Witgen, Brent M; Lifshitz, Jonathan; Grady, M Sean (2006) Inbred mouse strains as a tool to analyze hippocampal neuronal loss after brain injury: a stereological study. J Neurotrauma 23:1320-9
Farkas, Orsolya; Lifshitz, Jonathan; Povlishock, John T (2006) Mechanoporation induced by diffuse traumatic brain injury: an irreversible or reversible response to injury? J Neurosci 26:3130-40