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Microglial-Neurovascular Dynamics and Regulation of Neurovascular Structure and Function

Award Number: R01NS122782
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: 08/01/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Microglial-Neurovascular Dynamics and Regulation of Neurovascular Structure and Function - Project Summary The brain makes up 2% of the body’s weight but uses 20% of the body’s energy that is observed from the delivery of blood through the dense network of the neurovasculature. Neurovascular function is critical for optimal brain function and altered neurovascular function contributes or brain pathology. Microglia ate brain- resident immune cells that respond to brain injuries and disease but their interactions with the vasculature has been poorly explored. In my preliminary data, I extensively characterized microglial interactions with the neurovasculature in the healthy brain. Specifically, I have found that about a third of the microglia population physically interact with the neurovasculature through their cell bodies which are more stationary than their processes. Interestingly, a deficiency of Trem2, a microglial-specific risk gene for AD, results in a significant increase in microglial-vascular interactions. Finally, pharmacological elimination of CSF1R-expressing cells such as microglia resulted in increased vascular size and cerebral blood flow suggesting modulatory roles for microglia on the vasculature. In this project, I will further investigate this by (i) determining specific roles for microglia in regulating vascular structure and function; (ii) determining the requirement for astrocytic endfeet calcium signaling in mediating microglial-dependent vascular structure and functional regulation, and (iii) determine TREM2 roles in microglial-vascular interactions including vascular amyloid deposition in AD. These studies will provide insights into the cellular, molecular and mechanistic basis of microglial regulation of neurovascular structure and function.


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 = $401,361 )
2025	2025	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	6/27/2025	NON-COMPETING CONTINUATION	$401,361
														Subtotal = $401,361

Issue Date FY: 2024 ( Subtotal = $389,320 )
2024	2024	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 EMMET ST N	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	5/8/2024	NON-COMPETING CONTINUATION	$389,320
														Subtotal = $389,320

Issue Date FY: 2023 ( Subtotal = $401,361 )
2023	2023	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	5/11/2023	NON-COMPETING CONTINUATION	$401,361
														Subtotal = $401,361

Issue Date FY: 2022 ( Subtotal = $401,361 )
2022	2022	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/17/2022	NON-COMPETING CONTINUATION	$401,361
														Subtotal = $401,361

Issue Date FY: 2021 ( Subtotal = $401,361 )
2021	2021	RECTOR & VISITORS OF THE UNIVERSITY OF VIRGINIA	1001 N EMMET ST	CHARLOTTESVILLE	VA	22903	CHARLOTTESVILLE CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/13/2021	NEW	$401,361
														Subtotal = $401,361

Grand Total All Awards = $1,994,764

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Microglial-Neurovascular Dynamics and Regulation of Neurovascular Structure and Function

Award Number: R01NS122782

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: 08/01/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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