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CORTICOSPINAL MECHANISMS FOR HIGH FAT DIET IMPEDING STROKE RECOVERY

Award Number: R01NS114651
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: 12/15/2019
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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CORTICOSPINAL MECHANISMS FOR HIGH FAT DIET IMPEDING STROKE RECOVERY - SUMMARY / ABSTRACT Comorbid metabolic conditions of stroke, including obesity and diabetes, worsen stroke injury and reduce the capacity for stroke recovery. Given that stroke and these comorbid metabolic conditions are highly prevalent, the goal of this project is to understand how their interactions mechanistically affect the corticospinal motor system using high fat diet (HFD) as a model of metabolic disruption. In preliminary testing, HFD profoundly worsens behavioral motor recovery after experimental stroke. HFD and experimental stroke also cause an abnormal and profound emergence of lower extremity motor commands in areas of motor cortex that show little of these commands in otherwise healthy conditions or with experimental stroke injury and control diet. These abnormal lower extremity motor commands appear to be mechanistically due to increased synaptic signaling within the corticospinal system at connections that have not been well identified in this pathway. Volitional skilled motor control of the extremities is primarily achieved by the corticospinal tract and this pathway is often damaged by stroke resulting in severe disability. The canonical view of the corticospinal tract is that it is a synaptic circuit, from layer 5 pyramidal cells (L5PCs) in motor cortex, to spinal motor neurons that themselves signal skeletal muscle (CST= L5PCs→ spinal motor neurons→ skeletal muscle). L5PCs that project to cervical spinal cord (cervical-projecting) are thought to control upper extremity function whereas L5PCs that project to lumbar spinal cord (lumbar-projecting) are thought to control lower extremity function. What is less known is whether single L5PCs can innervate cervical and lumbar levels of spinal cord and thus contribute motor control to upper and lower extremities. Similarly, it is recognized that L5PCs synapse on one-another (L5PCs→L5PCs) however it is not known whether this is true between cervical-projecting L5PCs and lumbar-projecting L5PCs during stroke recovery. Experiments here will test these seldom studied connections of the corticospinal system because they may underpin the abnormal emergence of lower extremity motor commands that arise when HFD is combined with experimental stroke. To investigate these hypotheses, we propose 3 aims: Aim 1. Determine whether distribution and in vivo signaling of cervical- and lumbar-projecting L5PCs can support abnormal emergence of hindlimb motor commands in anterior motor cortex when HFD is combined with experimental stroke. Aim 2. Test whether physiology of cervical- and lumbar-projecting L5PCs can support abnormal emergence of hindlimb motor commands in anterior motor cortex when HFD is combined with experimental stroke. Aim 3. Test timing, duration and persistence of HFD to exacerbate upper and lower extremity deficits after experimental stroke injury. This proposal aims to determine the corticospinal circuits responsible for this abnormal plasticity of lower extremity motor control in order to guide its future targeted treatment as a novel therapy for stroke recovery in the context of clinically-relevant comorbid metabolic conditions.


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 = $328,717 )
2024	2024	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	5	9/20/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$23,722
2024	2024	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	5	7/1/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$341,109
2024	2024	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	1/12/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$304,995
2024	2023	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	4	7/1/2024	NON-COMPETING CONTINUATION	-$335,694
2024	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/12/2024	NON-COMPETING CONTINUATION	$0
2024	2022	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	7/1/2024	NON-COMPETING CONTINUATION	-$5,415
														Subtotal = $328,717

Issue Date FY: 2023 ( Subtotal = $335,694 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/9/2022	NON-COMPETING CONTINUATION	$302,125
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	2/1/2023	NON-COMPETING CONTINUATION	$33,569
														Subtotal = $335,694

Issue Date FY: 2022 ( Subtotal = $312,860 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	12/3/2021	NON-COMPETING CONTINUATION	$302,124
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	3/24/2022	NON-COMPETING CONTINUATION	$33,570
2022	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	12/31/2021	SUPPLEMENT FOR EXPANSION	-$22,834
														Subtotal = $312,860

Issue Date FY: 2021 ( Subtotal = $413,499 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/10/2020	NON-COMPETING CONTINUATION	$300,689
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	4/16/2021	SUPPLEMENT FOR EXPANSION	$79,400
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/25/2021	NON-COMPETING CONTINUATION	$33,410
														Subtotal = $413,499

Issue Date FY: 2020 ( Subtotal = $560,244 )
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/18/2020	SUPPLEMENT FOR EXPANSION	$226,676
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/5/2019	NEW	$333,568
														Subtotal = $560,244

Grand Total All Awards = $1,951,014

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CORTICOSPINAL MECHANISMS FOR HIGH FAT DIET IMPEDING STROKE RECOVERY

Award Number: R01NS114651

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: 12/15/2019

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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