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The Role of Microglia in Epilepsy

Award Number: R01NS088627
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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SUMMARY Our initial grant funding focused on the earliest period following experimentally-induced seizures. We documented robust physical interactions between microglia and neurons in epileptic contexts and concluded that microglia provide beneficial functions in the acute seizures. In this renewal, we will further investigate microglial activities in the epileptic brain in vivo and combine cellular and functional imaging with electrophysiological and behavioral studies in experimental mouse seizure models. We will extend our findings from the initial funding cycle to further characterize microglial activities in the epileptic brain following seizures and provide further evidence of microglial neuroprotection in the acute phase of kainic acid (KA)-induced seizures. In addition, we will investigate microglial roles in the epileptic brain in the chronic phase of epilepsy using microglial ablation and chemogenetic DREADD approaches. Our central hypothesis is that microglia play opposing roles during the acute phase of seizures and the chronic phase of epileptogenesis. This hypothesis will be tested along the following specific aims: In Aim 1, we will investigate the dynamics and function of seizure-induced microglial process pouches. In Aim 2, we will determine microglial contributions to epileptogenesis. Finally, in Aim 3, we will ascertain opposing microglial roles in acute seizures and chronic epilepsy using DREADD approaches. When completed, this grant will extend the findings of the initial funding to elucidate the beneficial roles for microglia in the acute phase of seizures Furthermore, this renewal will highlight detrimental contributions by microglia in promoting seizure-induced neurogenesis, neuronal sprouting, neuronal excitability and spontaneous seizures in the chronic phase of seizures. This study will not only improve our understanding of microglial mechanism to epileptogenesis but also demonstrate that microglia are potential therapeutic targets for the treatment seizures and epilepsy.


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 = -$1 )
2025	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	2/24/2025	NON-COMPETING CONTINUATION	-$1
2025	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	10/30/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = -$1

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	9/11/2024	NON-COMPETING CONTINUATION	-$181,437
2024	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	12	9/11/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$181,437
2024	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	2/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $392,762 )
2023	2023	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	11	9/6/2023	NON-COMPETING CONTINUATION	$0
2023	2023	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	3/1/2023	NON-COMPETING CONTINUATION	$392,762
														Subtotal = $392,762

Issue Date FY: 2022 ( Subtotal = $392,762 )
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	4/22/2022	NON-COMPETING CONTINUATION	$39,277
2022	2022	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	2/17/2022	NON-COMPETING CONTINUATION	$353,485
														Subtotal = $392,762

Issue Date FY: 2021 ( Subtotal = $392,762 )
2021	2021	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	2/22/2021	NON-COMPETING CONTINUATION	$392,762
														Subtotal = $392,762

Issue Date FY: 2020 ( Subtotal = $392,762 )
2020	2020	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	4/15/2020	NON-COMPETING CONTINUATION	$392,762
														Subtotal = $392,762

Issue Date FY: 2019 ( Subtotal = $392,762 )
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	3/14/2019	COMPETING CONTINUATION	$392,762
2019	2019	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	7	7/5/2019	COMPETING CONTINUATION	$29,668
2019	2018	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	7/5/2019	NON-COMPETING CONTINUATION	-$29,668
2019	2018	MAYO CLINIC	200 FIRST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	3/12/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $392,762

Issue Date FY: 2018 ( Subtotal = $347,813 )
2018	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	2/16/2018	NON-COMPETING CONTINUATION	$313,031
2018	2018	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	6	4/25/2018	NON-COMPETING CONTINUATION	$34,782
2018	2017	MAYO CLINIC	200 1ST ST SW	ROCHESTER	MN	55905	OLMSTED	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	11/10/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$252,952
2018	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/10/2017	NON-COMPETING CONTINUATION	-$252,952
2018	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	2/14/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $347,813

Issue Date FY: 2017 ( Subtotal = $335,677 )
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/21/2017	NON-COMPETING CONTINUATION	$33,568
2017	2017	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	3/6/2017	NON-COMPETING CONTINUATION	$302,109
														Subtotal = $335,677

Issue Date FY: 2016 ( Subtotal = $333,736 )
2016	2016	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/3/2016	NON-COMPETING CONTINUATION	$333,736
														Subtotal = $333,736

Issue Date FY: 2015 ( Subtotal = $324,441 )
2015	2015	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	1/13/2015	NON-COMPETING CONTINUATION	$324,441
														Subtotal = $324,441

Issue Date FY: 2014 ( Subtotal = $324,750 )
2014	2014	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLAZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/25/2014	NEW	$324,750
														Subtotal = $324,750

Grand Total All Awards = $3,630,226

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The Role of Microglia in Epilepsy

Award Number: R01NS088627

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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