This $615,627 federal Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program will support research to interrogate the methylome, or DNA methylation patterns, as a potential indicator of long-term neurobehavioral recovery in pediatric traumatic brain injury (TBI) patients. The project aims to: 1) determine the association between pediatric TBI and...
The National Institute of Neurological Disorders and Stroke (NINDS) awarded a $628,133 Project Grant (CFDA 93.853 - Extramural Research Programs in the Neurosciences and Neurological Disorders) to Rutgers, The State University, to conduct research on "Metabolic Mechanisms of Recovery in Mild TBI". The research aims to determine if activation of the CYPIN protein can be targeted after mild traumatic brain injury (TBI) to promote functional recovery in mice. The project will...
This Project Grant award from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), under the "Discovery and Applied Research for Technological Innovations to Improve Human Health" (CFDA 93.286) program, is aimed at developing and assessing novel frameworks to accurately predict functional outcomes and recovery trajectories for patients with moderate-to-severe traumatic brain injury (TBI). The $389,813 award, spanning August 2024 to July 2026, will leverage...
This Project Grant award of $499,999 from the National Institute on Disability, Independent Living, and Rehabilitation Research (CFDA 93.433 - ACL National Institute on Disability, Independent Living, and Rehabilitation Research) aims to evaluate the efficacy of a novel rehabilitation intervention called "Tools for Recovery and Clinical Care" (ON-TRACC) in improving quality of life and function for individuals experiencing persistent post-concussive symptoms, especially cognitive...
The University of Pittsburgh is receiving a $437,250 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program. The grant aims to provide proof-of-concept evidence that retinoic acid (RA) can attenuate cholinergic deficits and white matter connectivity impairments after traumatic brain injury (TBI). The two-year project will: 1) determine if RA treatment...
This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, provides $404,100.00 to The General Hospital Corporation (Massachusetts General Hospital) for research on mechanisms of chronic blood-brain barrier dysfunction after traumatic brain injury (TBI). The key objectives are to: 1) identify an endothelial RIPK1-RIPK3-IL-1β pathway driving...
The National Institute of Neurological Disorders and Stroke (NINDS) awarded a $423,624 Project Grant under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) to Rutgers, The State University to conduct research on sleep and circadian rhythm disorders following traumatic brain injury (TBI). The project aims to use the Drosophila melanogaster genetic model to 1) identify genes that contribute to TBI-induced changes in sleep and circadian rhythms, and...
This $317,119 Project Grant award from the National Institute of Child Health and Human Development (CFDA 93.865 - Child Health and Human Development Extramural Research) to the University of Texas at Austin aims to demonstrate the feasibility of a real-time, personalized brain state-dependent transcranial magnetic stimulation (TMS) system to enhance post-stroke hand rehabilitation. The key objectives are to: 1) Establish the feasibility of delivering TMS stimulation only during personalized...
This federal Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, provides $405,000.00 to the University of Cincinnati to conduct research on the effects of traumatic brain injury (TBI) on serotonin (5-HT) neuron function and identity. The key objectives are to: 1) Identify and characterize TBI-induced changes in the transcriptional profiles of...
This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) federal grant program, provides $1,250,387 to test and develop a tetrapeptide called ACSDKP as a novel treatment for traumatic brain injury (TBI). The project aims to investigate the mechanisms by which ACSDKP can enhance functional recovery after TBI, including by reducing neuroinflammation,...
INVESTIGATION OF COGNITIVE AND AFFECTIVE DEFICITS POST TBI USING MULTIMODAL FLEXIBLE NEURAL PROBES - PROJECT SUMMARY: TRAUMATIC BRAIN INJURY (TBI) IS A GLOBAL HEALTH CRISIS, AND PERSISTENT COGNITIVE-AFFECTIVE SYMPTOMS ARE COMMON AMONG TBI SURVIVORS. METHYLPHENIDATE (MPH), A DOPAMINE (DA) TRANSPORTER (DAT) INHIBITOR, HAS DEMONSTRATED IMPROVED OUTCOMES WITH SEX DIFFERENCES IN THE RESPONSE. OUR PRIOR WORK SUGGESTS DAILY MPH TREATMENT IN RATS WITH EXPERIMENTAL TBI HELPS NORMALIZE ELECTRICALLY EVOKED STRIATAL DA, BUT THE EFFECT ON STRIATAL BASAL DA LEVEL AND THE POSTSYNAPTIC STRIATAL MEDIUM SPINY NEURONS (MSNS) HAS NOT BEEN INVESTIGATED. THE OTHER MAJOR STRIATAL INPUT, GLUTAMATERGIC CORTICAL NEURONS, CAN CONTRIBUTE TO TBI-INDUCED EXCITOTOXICITY. WE HYPOTHESIZE ONGOING GLU-INDUCED EXCITOTOXICITY POST-TBI NOT ONLY REDUCES TONIC [DA] FIRING BUT ALSO LIMITS MSN OUTFLOW VIA MSN DAMAGE, CONSEQUENTLY LEADING TO DA TRANSMISSION DYSFUNCTION AND COGNITIVE-AFFECTIVE DEFICITS THAT ARE RESCUED BY MPH. A DETAILED INVESTIGATION OF THE STRIATUM, INCLUDING ITS INPUTS (DA/GLU) AND OUTPUT (MSN FIRING) IS CRITICAL TO UNDERSTAND TBI-INDUCED STRIATAL DAMAGE, BEHAVIOR EFFECTS, MPH MECHANISMS AND SEX DIFFER- ENCES TO CUSTOMIZE TREATMENT FOR TBI PATIENTS. TO ENABLE SUCH INVESTIGATION, WE WILL DEVELOP A MULTIMODAL MI- CROELECTRODE ARRAY (MEA) TO MONITOR THE RAT STRIATUM FOR 3 WKS AFTER TBI AND MPH, AND CORRELATE MSN NEURAL ACTIVITY, BASAL [DA] AND [GLU] TO MOLECULAR AND BEHAVIORAL ASSESSMENTS. CURRENT STATE OF ART MEAS TYPICALLY USE ONE MODALITY OR ASSESS ONE ANALYTE, AND SUFFER FROM CHRONIC RECORDING OR SENSING DEGRADATIONS DUE TO BIOFOULING, INFLAMMATORY TISSUE REACTION, OR SENSOR/ELECTRODE MATERIAL DEGRADA- TION. TBI EXERTS ADDITIONAL MECHANICAL AND BIOCHEMICAL CHALLENGES TO THE IMPLANTED DEVICE, AND ITS EFFECT ON DEVICE FUNCTION IS UNKNOWN. BY PAIRING NOVEL SQUARE WAVE VOLTAMMETRY WITH A POLY(3,4-ETHYLENEDIOXYTHIO- PHENE)/ACID FUNCTIONALIZED CARBON NANOTUBE (PEDOT/CNT) COATING, WE HAVE ACHIEVED BASAL DA SENSING IN VIVO FOR 3 WKS. MEANWHILE, AN INNOVATIVE NANOPARTICLE TECHNOLOGY SHOWS PROMISE IN STABILIZING GLU OXIDASE, ALLOWING FOR SELECTIVE FUNCTIONALIZATION OF INDIVIDUAL ELECTRODE SITES FOR GLU SENSING. ADDITIONALLY, FLEXIBLE SUBSTRATES AND ANTIFOULING COATINGS HAVE INDEPENDENTLY SHOWN BENEFITS IN THE SEAMLESS TISSUE INTEGRATION OF MEAS. THE GOAL OF THIS PROJECT IS TO TAKE ADVANTAGE OF THESE NOVEL TECHNOLOGIES TO BUILD A FLEXIBLE MEA THAT CAN CHRONICALLY INTERROGATE STRIATAL DA & GLU NEUROTRANSMISSION WHILE RECORDING STRIATAL MSN FIRING, IN ORDER TO ADVANCE OUR UNDERSTANDING OF BIOLOGICAL MECHANISMS UNDERLYING SEX-SPECIFIC COGNITIVE-AFFECTIVE SYMPTOMS AND TREATMENT POST-TBI. TO ACCOMPLISH THIS GOAL, WE WILL 1) DEVELOP AND OPTIMIZE A FLEXIBLE MULTIMODAL MEA FOR IN VIVO SENSING OF BASAL [DA] AND [GLU], AND NEURAL RECORDING IN NAIVE RATS, 2) INVESTIGATE TBI EFFECTS ON DEVICE PERFORMANCE, AND 3) EXPLORE STRIATAL MECHANISMS OF COGNITIVE-AFFECTIVE SYMPTOMS AFTER TBI AND MPH TREATMENT USING RECORDED STRIATAL NEURAL ACTIVITY AND BASAL [DA/GLU] PAIRED WITH BEHAVIORAL, MOLECULAR, AND HISTOLOGICAL ANALYSES TO BUILD A HOLISTIC MECHANISTIC PICTURE OF THE STRIATUM POST TBI AND TREATMENT.