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Hemorheological Factors in Cerebral Ischemia

Award Number: R01NS020989
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: 07/01/1984
PERIOD OF PERFORMANCE END DATE: 04/30/2024

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Hemorheological Factors in Cerebral Ischemia - Project Summary/Abstract This project (begun in 1984) continues its long-term goal to enhance understanding of stroke by novel mechanistic investigations. Our principal interest is cerebral microhemorrhage, the pathological substrate of cerebral microbleeds and the major hemorrhagic component of microvascular cerebral disease. The proposed project will utilize a combination of novel animal models of cerebral microbleeds, new cell culture models of microbleeds that address red blood cell (RBC)-endothelial interactions, and cutting edge analytic techniques. Our objective is to identify mechanisms that broadly impact development of cerebral microbleeds as well as those more specifically related to individual vascular risk factors for microbleeds, The project investigators are a unique group of investigators with expertise in stroke neurology, vascular neurobiology, nephrology, bioengineering, and biostatistics, all with capabilities relevant to animal and cell culture studies. We specifically propose the following aims: Specific Aim 1: To determine mechanisms of cerebral microhemorrhage in vivo. Specific Aim 2: To delineate paracellular mechanisms of RBC passage across brain microvascular endothelium in vitro. Specific Aim 3: To delineate transcellular mechanisms of RBC passage across brain microvascular endothelium. The proposed studies are designed as a series of synergistic experiments that combine in vivo and in vitro studies to provide novel insights into microvascular brain disease. We will use a combination of studies of microvascular physiology and neuropathology to identify the vascular source of cerebral microbleeds and to delineate those interactions between RBC and brain microvascular endothelium that immediately precede establishment of cerebral microbleeds. The project is a direct extension of work we completed during the most recent funding period of this grant and incorporate new animal models of cerebral microbleeds and novel conceptual models describing microbleed pathogenesis. Our in vivo studies will address mechanisms of aging, hypertension, and chronic kidney disease in microbleed development, along with the roles of microglia and matrix metalloproteinase-9. This project directly addresses the highly prevalent problem of hemorrhagic microvascular disease of the brain. Our work and that of others have shown the near-ubiquitous presence of microhemorrhagic changes in aging human brain. Our multi-disciplinary team of investigators are uniquely capable of taking this project to completion, directly testing our microbleed conceptual models in the expectation that robust insights will emerge helping to transform the management of microvascular disorders of the brain which, along with Alzheimer’s disease, represents the most common cause of neurological morbidity of aging.


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: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	34	8/27/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $609,018 )
2022	2022	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	34	4/22/2022	NON-COMPETING CONTINUATION	$609,018
														Subtotal = $609,018

Issue Date FY: 2021 ( Subtotal = $608,107 )
2021	2021	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	33	5/4/2021	NON-COMPETING CONTINUATION	$608,107
														Subtotal = $608,107

Issue Date FY: 2020 ( Subtotal = $607,221 )
2020	2020	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	32	4/15/2020	NON-COMPETING CONTINUATION	$607,221
														Subtotal = $607,221

Issue Date FY: 2019 ( Subtotal = $606,362 )
2019	2019	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	31	4/12/2019	NON-COMPETING CONTINUATION	$606,362
														Subtotal = $606,362

Issue Date FY: 2018 ( Subtotal = $619,153 )
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	30	9/27/2018	COMPETING CONTINUATION	$31,336
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	30	6/19/2018	COMPETING CONTINUATION	$513,186
2018	2018	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	30	7/2/2018	COMPETING CONTINUATION	$105,967
2018	2016	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	29	9/27/2018	EXTENSION WITH OR WITHOUT FUNDS	-$31,336
2018	2016	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	29	6/18/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
2018	2016	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	29	5/2/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $619,153

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	29	12/9/2016	EXTENSION WITH OR WITHOUT FUNDS	$229,170
2017	2015	UNIVERSITY OF CALIFORNIA, IRVINE	141 INNOVATION DR STE 250	IRVINE	CA	92617	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	28	12/9/2016	NON-COMPETING CONTINUATION	-$229,170
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $546,630 )
2016	2016	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	29	4/18/2016	EXTENSION WITH OR WITHOUT FUNDS	$546,630
														Subtotal = $546,630

Issue Date FY: 2015 ( Subtotal = $546,630 )
2015	2015	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	28	4/14/2015	NON-COMPETING CONTINUATION	$546,630
														Subtotal = $546,630

Issue Date FY: 2014 ( Subtotal = $543,055 )
2014	2014	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	27	4/18/2014	NON-COMPETING CONTINUATION	$543,055
														Subtotal = $543,055

Issue Date FY: 2013 ( Subtotal = $526,076 )
2013	2013	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	26	5/20/2013	NON-COMPETING CONTINUATION	$35,436
2013	2013	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	26	5/3/2013	NON-COMPETING CONTINUATION	$490,640
														Subtotal = $526,076

Issue Date FY: 2012 ( Subtotal = $543,387 )
2012	2012	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	8/20/2012	COMPETING CONTINUATION	$543,387
														Subtotal = $543,387

Issue Date FY: 2011 ( Subtotal = $326,922 )
2011	2011	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	3/16/2011	NON-COMPETING CONTINUATION	$300,234
2011	2011	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	24	6/1/2011	NON-COMPETING CONTINUATION	$26,688
														Subtotal = $326,922

Issue Date FY: 2010 ( Subtotal = $330,259 )
2010	2010	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	3/17/2010	NON-COMPETING CONTINUATION	$330,259
														Subtotal = $330,259

Issue Date FY: 2009 ( Subtotal = $428,844 )
2009	2009	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	22	3/25/2009	NON-COMPETING CONTINUATION	$333,594
2009	2009	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Trans-NIH Recovery Act Research Support	001	22	9/23/2009	SUPPLEMENT FOR EXPANSION	$95,250
														Subtotal = $428,844

Issue Date FY: 2008 ( Subtotal = $333,594 )
2008	2008	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	3/19/2008	NON-COMPETING CONTINUATION	$333,594
														Subtotal = $333,594

Issue Date FY: 2007 ( Subtotal = $333,594 )
2007	2007	UNIVERSITY OF CALIFORNIA, IRVINE	2301 BERKELEY PLACE	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	3/20/2007	COMPETING CONTINUATION	$333,594
														Subtotal = $333,594

Issue Date FY: 2004 ( Subtotal = $338,400 )
2004	2004	UNIVERSITY OF CALIFORNIA, IRVINE							Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19	6/30/2004	NON-COMPETING CONTINUATION	$338,400
														Subtotal = $338,400

Issue Date FY: 2003 ( Subtotal = $338,400 )
2003	2003	UNIVERSITY OF CALIFORNIA, IRVINE							Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	7/7/2003	NON-COMPETING CONTINUATION	$338,400
														Subtotal = $338,400

Issue Date FY: 2002 ( Subtotal = $338,400 )
2002	2002	UNIVERSITY OF CALIFORNIA, IRVINE	UC IRVINE	IRVINE	CA	92717		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	7/18/2002	NON-COMPETING CONTINUATION	$338,400
														Subtotal = $338,400

Issue Date FY: 2001 ( Subtotal = $338,400 ) (Continued on the next page)
Grand Total All Awards = $9,661,370

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Hemorheological Factors in Cerebral Ischemia

Award Number: R01NS020989

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: 07/01/1984

PERIOD OF PERFORMANCE END DATE: 04/30/2024

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