Saturday, April 20, 2024 4/20/2024

Modulating the post-stroke inflammatory response to improve outcome in models of cerebral ischemia

Award Number: R01NS100180
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Modulating the post-stroke inflammatory response to improve outcome in models of cerebral ischemia ABSTRACT inflammatory responses. Stroke is a multiphasic process, with an initial ischemic phase followed by secondary progression of injury from Following ischemia, microglia and macrophages accumulate in the ischemic area and produce inflammatory mediators and chemokines that initially recruit peripheral macrophages, neutrophils, dendritic cells, and later T and B cells. This post-stroke inflammatory response is both beneficial and injurious, as multiple and simultaneous immune pathways in distinct immune cell populations generate both beneficial and maladaptive immune responses. Because the time window of intervention of thrombolytic strategies is limited after onset of ischemia, and because attempts at neuroprotection after stroke have not shown positive results, the post-stroke inflammatory response represents an attractive target for intervention to reduce brain injury and accelerate functional recovery. The identification of specific immune pathways activated after stroke that could be modulated therefore represents an opportunity to improve and accelerate recovery after stroke. In previous studies, we have focused on the beneficial effects of inhibiting COX-2/PGE2 inflammatory signaling through the myeloid PGE2 EP2 receptor. In these studies, we identified Triggering Receptor Expressed on Myeloid cells-1, or TREM1, as highly regulated by inflammatory PGE2 EP2 signaling. TREM1 is an inflammatory membrane receptor that is expressed only on myeloid lineage cells and is unique in its function as an amplifier of maladaptive inflammatory responses. Our preliminary data suggest that this immune signaling cascade enhances innate immune responses after cerebral ischemia days after stroke. Using a combination of pharmacological and conditional knockout strategies to isolate the contribution of peripheral immune cells to stroke, we propose to identify the mechanisms of action of TREM1 signaling after stroke and test the hypothesis that inhibition of this pathway in the days after stroke will enhance brain repair and accelerate recovery.


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: 2023 ( Subtotal = $0 )
2023	2021	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	10/13/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $484,396 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/18/2021	NON-COMPETING CONTINUATION	$484,396
														Subtotal = $484,396

Issue Date FY: 2020 ( Subtotal = $552,810 )
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	3	5/11/2020	NON-COMPETING CONTINUATION	$518,800
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/31/2020	SUPPLEMENT FOR EXPANSION	$33,751
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/2/2020	SUPPLEMENT FOR EXPANSION	$215
2020	2020	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	4/15/2020	SUPPLEMENT FOR EXPANSION	$44
														Subtotal = $552,810

Issue Date FY: 2019 ( Subtotal = $382,667 )
2019	2019	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	4/23/2019	NON-COMPETING CONTINUATION	$382,667
														Subtotal = $382,667

Issue Date FY: 2018 ( Subtotal = $382,574 )
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	3/27/2018	NEW	$0
2018	2018	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	10/31/2017	NEW	$382,574
														Subtotal = $382,574

Grand Total All Awards = $1,802,447

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Modulating the post-stroke inflammatory response to improve outcome in models of cerebral ischemia

Award Number: R01NS100180

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer