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Direct visualization of longitudinal effects of drug therapy on white matter in diffuse injured brain

Award Number: R21NS090131
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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DESCRIPTION (provided by applicant): This project will provide high-content data that will be used for both basic and preclinical research. BASIC RESEARCH ASPECT: We will use a novel method of high-resolution, subcortical, in vivo imaging to fill critical gaps in knowledge about th dynamics of diffuse traumatic brain injury at a cellular level in subcortical white matter in live mice over a 60-day period post-injury. This knowledge will give us new insights into understanding the progressive degeneration that happens after TBI and for optimizing therapeutic windows for future combination drug therapy. We will obtain these images in live mice using a permanently implanted microlens positioned over a subcortical white matter tract and periodically image through this lens using a multiphoton microscope. We will reveal previously unseen spatio-temporal dynamics of axon degeneration, microglia infiltration and activation, and microvascular changes with cellular resolution in this region. PRECLINICAL ASPECT: We will also use 3 key outcomes from our observations to evaluate the efficacy of a drug which is now in preclinical trials. This drug, minocycline, is an FDA-approved antibiotic that has reduced axonal loss and microglial activation when given in a single dose within a few hours of experimental traumatic brain injury in mice. We hypothesize that a dose given 3 days post-injury will have the same therapeutic benefits of significantly (1) reducing axonal loss and (2) reducing microglial activation. We further hypothesize that minocycline will result in significant improvement in microcirculation rates. Widening the therapeutic window for this promising drug will better position it for translation to the clinic.


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: 2019 ( Subtotal = -$124 )
2019	2016	LOUISIANA TECH UNIVERSITY	RAIL ROAD AVE WYLY TOWER 1620	RUSTON	LA	71272	LINCOLN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/18/2018	SUPPLEMENT FOR EXPANSION	-$124
														Subtotal = -$124

Issue Date FY: 2016 ( Subtotal = $189,193 )
2016	2016	LOUISIANA TECH UNIVERSITY	PO BOX 7924	RUSTON	LA	71272	LINCOLN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	8/8/2016	SUPPLEMENT FOR EXPANSION	$50,000
2016	2016	LOUISIANA TECH UNIVERSITY	PO BOX 7924	RUSTON	LA	71272	LINCOLN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	8/5/2016	NON-COMPETING CONTINUATION	$139,193
														Subtotal = $189,193

Issue Date FY: 2015 ( Subtotal = $211,769 )
2015	2015	LOUISIANA TECH UNIVERSITY	PO BOX 7924	RUSTON	LA	71272	LINCOLN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/6/2015	NEW	$211,769
														Subtotal = $211,769

Grand Total All Awards = $400,838

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Direct visualization of longitudinal effects of drug therapy on white matter in diffuse injured brain

Award Number: R21NS090131

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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