Monday, June 30, 2025 6/30/2025

Role of Peripheral Inflammation in TBI Pathobiology

Award Number: R01NS121261
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 01/31/2027

Group Awards By:

View Award Description

Role of Peripheral Inflammation in TBI Pathobiology - Abstract Inflammation is associated with most brain diseases and is thought to contribute to disease pathology. Unregulated inflammation can contribute to secondary brain damage and neurodegeneration following traumatic brain injury (TBI). While the majority of TBI research has focused on the role of central inflammation in TBI pathophysiology, the contribution of peripheral inflammation is under investigated. A detrimental role for peripheral inflammation was first demonstrated by Helen Bramlett and colleagues, who reported that intraperitoneal administration of pro-inflammatory cytokines to TBI animals can result in poor outcome. Previous studies have shown that vagus nerve stimulation can reduce both peripheral inflammation and mortality following bacterial lipopolysaccharide (LPS) injection, a widely used model to study inflammation, sepsis and organ failure. Subsequent studies have shown that release of acetylcholine from vagus efferents stimulates α7 nicotinic acetylcholine receptors (α7nAChR) on inflammatory cells, leading to reduced release of pro-inflammatory cytokines into the circulation. As acetylcholine is rapidly degraded after release, and α7nAChR undergo rapid desensitization, additional mechanisms may be involved in regulating peripheral inflammation. We examined the vagus efferents and their cell bodies located in the dorsal motor nucleus of vagus (DMN) for the expression of neuropeptides, which are often co-released with neurotransmitters and have a relatively longer half-lives. We have found that cocaine- and amphetamine-regulated transcript (CART) peptide (CARTp) is expressed at high levels in DMN neurons. We propose to test the hypothesis that that CARTp acts to regulate peripheral inflammation and can be used to improve TBI outcome. We will first test this hypothesis by examining the role of vagus CARTp in TBI-associated inflammation using neutralizing CARTp antibodies and administration of exogenous CARTp targeted to the spleen. Using CRISPR-Cas, we will delete the Cartpt gene in the DMN, and will measure the levels of circulating pro-inflammatory cytokines following TBI. We will then test the therapeutic potential of CARTp as a treatment for TBI by examining its effect on inflammation, blood brain barrier (BBB) permeability, and inflammatory cell infiltration into the injured brain. Finally, we will examine if post-TBI CARTp administration can reduce neuronal loss and improve cognitive outcome. Sex as a biological variable will be assessed. The results from these studies will have implications not only for TBI, as well as for the numerous other diseases in which inflammation is a contributor.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $459,015 )
2025	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/17/2025	NON-COMPETING CONTINUATION	$459,015
														Subtotal = $459,015

Issue Date FY: 2024 ( Subtotal = $494,716 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/26/2024	NON-COMPETING CONTINUATION	$459,015
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/3/2024	NON-COMPETING CONTINUATION	$35,701
														Subtotal = $494,716

Issue Date FY: 2023 ( Subtotal = $510,015 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/2/2023	NON-COMPETING CONTINUATION	$510,015
														Subtotal = $510,015

Issue Date FY: 2022 ( Subtotal = $510,015 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/20/2022	NEW	$510,015
														Subtotal = $510,015

Grand Total All Awards = $1,973,761

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Role of Peripheral Inflammation in TBI Pathobiology

Award Number: R01NS121261

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 01/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer