Thursday, December 18, 2025 12/18/2025

Role of Myeloid And CD4+ T Immune Cells in Post-Traumatic Plasticity

Award Number: R01NS121287
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: 12/01/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Role of Myeloid And CD4+ T Immune Cells in Post-Traumatic Plasticity - ABSTRACT Traumatic brain injury (TBI) impacts millions of Americans each year and can lead to cognitive dysfunction, difficulty with sensory processing, sleep disruption, and the development of epilepsy. One common neural outcome of TBI is the development of electrophysiological abnormalities that can lead to post-traumatic epilepsy (PTE) or disruptions in sleep architecture. However, the mechanisms by which these neurological deficits arise as a consequence of TBI remain poorly understood. Preliminary evidence indicates that inflammation contributes to the electrophysiological abnormalities that underlie PTE and sleep disruption in a mouse model of moderate TBI. Indeed, TBI is characterized by both the activation of glial cells like astrocytes and microglia and by the infiltration of peripheral immune cells like monocyte-derived macrophages and T-cells. While neuroinflammation occurs immediately in the cortical region of acute injury, secondary neuroinflammation develops slowly in the ipsilateral thalamus, presumably as a result of loss of intimate reciprocal connections between cortex and thalamus. Because the cortico-thalamo- cortical (CTC) circuit plays a key role in cognition, sleep, and seizures, which are all impacted by TBI, the delayed neural plasticity in this circuit is a good model for teasing apart the interaction between the immune cells and neural circuits after TBI. The role of peripheral immune cells is particularly understudied in the context of TBI-derived electrophysiological deficits like PTE and sleep disruption. We propose to use a controlled-cortical impact mouse model of moderate TBI to determine the role of delayed infiltration of monocyte-derived macrophages and CD4+ T cells in secondary neuronal loss (Aim 1), excitation/inhibition imbalance in the cortico-thalamic circuit (Aim 2), and the development of electrographic abnormalities such as sleep disruption and PTE (Aim 3). To do so, we will combine cutting-edge tools from both neuroscience and immunology, including genetic manipulations, flow cytometry, 3D imaging of immune-neural interactions, synaptic physiology in brain slices, and chronic wireless EEG recordings. Funding of this study will enable us to better understand how the immune system interacts with neural circuits after TBI to cause the development of neurological deficits. Given that there are treatments already available in clinic to block CD4+ T cells and macrophages, this study has the potential to rapidly impact how TBI is treated in human patients.


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: 2026 ( Subtotal = $371,161 )
2026	2026	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/12/2025	NON-COMPETING CONTINUATION	$371,161
														Subtotal = $371,161

Issue Date FY: 2025 ( Subtotal = $371,162 )
2025	2025	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/21/2024	NON-COMPETING CONTINUATION	$371,162
														Subtotal = $371,162

Issue Date FY: 2024 ( Subtotal = $543,669 )
2024	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	1/29/2024	SUPPLEMENT FOR EXPANSION	$71,820
2024	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	1/26/2024	SUPPLEMENT FOR EXPANSION	$71,820
2024	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/28/2023	NON-COMPETING CONTINUATION	$371,162
2024	2024	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	3	4/23/2024	NON-COMPETING CONTINUATION	$28,867
														Subtotal = $543,669

Issue Date FY: 2023 ( Subtotal = $412,402 )
2023	2023	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	1/31/2023	NON-COMPETING CONTINUATION	$41,240
2023	2023	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/1/2022	NON-COMPETING CONTINUATION	$371,162
														Subtotal = $412,402

Issue Date FY: 2022 ( Subtotal = $434,652 )
2022	2022	J.DAVID GLADSTONE INSTITUTES	1650 OWENS ST	SAN FRANCISCO	CA	94158	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/16/2021	NEW	$434,652
														Subtotal = $434,652

Grand Total All Awards = $2,133,046

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Role of Myeloid And CD4+ T Immune Cells in Post-Traumatic Plasticity

Award Number: R01NS121287

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: 12/01/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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