This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Traumatic brain injury (TBI) is the single most important cause of death and disability in children and adolescents, yet relatively little is known about the underlying mechanisms that distinguish pediatric brain injury from that in adults. It is understood the traumatic biomechanical injury to the immature brain can manifest as chronic cognitive and behavioral problems with a loss of developmental potential. Plasticity is defined as a mechanism by which the brain modifies cellular and network structure and function to respond to changes in the environment. There is increasing evidence that pediatric TBI can result in impaired plasticity and alterations in neurotransmission. Glutamate represents the major excitatory neurotransmitter in the central nervous system and is intimately involved in the acute pathophysiology of TBI, but also is critical for normal development and for neural plasticity. This application proposes to investigate the glutamatergic response to TBI in the immature brain, in particular, that which involves the N-methyl-D-aspartate (NMDA) receptor. The central hypothesis of this proposal is that dysfunction at the NMDA receptor underlies the loss of plasticity seen following developmental TBI, and that this perturbation can be measured molecularly (Specific Aims 1 and 2), electrophysiologically (Specific Aim 3) and cognitively (Specific Aim 4), using a well-characterized experimental model of pediatric TBI. By determining the post-injury time course of changes in this important neurotransmitter system, it will be possible to identify the window of impaired neural responsiveness at the NMDA receptor. Proper identification of this time period will then direct the final aim (Specific Aim 5) of this application, which is to utilize pharmacological agents that augment NMDA receptor neurotransmission to normalize the molecular profile of the developing brain and to alleviate behavioral and cognitive deficits. This proposal provides a unique opportunity to rigorously test an age-specific therapeutic strategy that is designed to be beneficial for the patient population most vulnerable to TBI, children.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-SBIB-L (40))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Los Angeles
Schools of Medicine
Los Angeles
United States
Zip Code
Walsh, Christine M; Ruoff, Leslie; Walker, Kathleen et al. (2017) Sleepless Night and Day, the Plight of Progressive Supranuclear Palsy. Sleep 40:
Dennis, Emily L; Rashid, Faisal; Faskowitz, Josh et al. (2017) MAPPING AGE EFFECTS ALONG FIBER TRACTS IN YOUNG ADULTS. Proc IEEE Int Symp Biomed Imaging 2017:101-104
Green, Shulamite A; Hernandez, Leanna; Bookheimer, Susan Y et al. (2017) Reduced modulation of thalamocortical connectivity during exposure to sensory stimuli in ASD. Autism Res 10:801-809
Ordóñez, Anna E; Loeb, Frances F; Zhou, Xueping et al. (2016) Lack of Gender-Related Differences in Childhood-Onset Schizophrenia. J Am Acad Child Adolesc Psychiatry 55:792-9
Green, Shulamite A; Hernandez, Leanna; Bookheimer, Susan Y et al. (2016) Salience Network Connectivity in Autism Is Related to Brain and Behavioral Markers of Sensory Overresponsivity. J Am Acad Child Adolesc Psychiatry 55:618-626.e1
Kodumuri, Nishanth; Sebastian, Rajani; Davis, Cameron et al. (2016) The association of insular stroke with lesion volume. Neuroimage Clin 11:41-5
Flournoy, John C; Pfeifer, Jennifer H; Moore, William E et al. (2016) Neural Reactivity to Emotional Faces May Mediate the Relationship Between Childhood Empathy and Adolescent Prosocial Behavior. Child Dev 87:1691-1702
Joshi, Shantanu H; Vizueta, Nathalie; Foland-Ross, Lara et al. (2016) Relationships Between Altered Functional Magnetic Resonance Imaging Activation and Cortical Thickness in Patients With Euthymic Bipolar I Disorder. Biol Psychiatry Cogn Neurosci Neuroimaging 1:507-517
Levine, Andrew J; Soontornniyomkij, Virawudh; Achim, Cristian L et al. (2016) Multilevel analysis of neuropathogenesis of neurocognitive impairment in HIV. J Neurovirol 22:431-41
Agis, Daniel; Goggins, Maria B; Oishi, Kumiko et al. (2016) Picturing the Size and Site of Stroke With an Expanded National Institutes of Health Stroke Scale. Stroke 47:1459-65

Showing the most recent 10 out of 550 publications