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Spinal Neuromodulation to Promote Physiologic and Molecular Plasticity in theInjured Spinal Cord

Award Number: R01NS132123
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: 09/20/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Spinal Neuromodulation to Promote Physiologic and Molecular Plasticity in theInjured Spinal Cord - Abstract There is growing interest in the use of electrical stimulation to promote the recovery of sensorimotor and autonomic function after neural injury. Previous research from our lab and others has demonstrated that stimulation of spinal lumbar segments activates central pattern generators, which, in turn, facilitates standing and walking. However, while there is extensive animal, pre-clinical, and clinical data examining the impact of lumbar stimulation, studies that apply neuromodulation to the cervical spinal cord for upper limb are very limited. Here, we propose that fundamental blind spots exist in the field of neuromodulation for upper limb, including where to stimulate anatomically, how to dose and, especially, mechanisms of action. The Horner lab has developed a clinically relevant rat model of cervical spinal cord injury and engineered a self-contained epidural stimulation device that can be deployed in freely behaving rats to stimulate sensorimotor circuitry from multiple surfaces of the spinal cord. Hence, we are well positioned to test critically important hypotheses on the role of cervical stimulation in the restoration of upper limb function. We present exciting preliminary data demonstrating that epidural stimulation of the cervical spinal cord improves forelimb function. The rationale for the proposed research is that the site of epidural stimulation provides unique access to motor circuitry. We hypothesize that ventral positioning of electrodes (VSS) will provide access to stimulate motor circuitry at the site of lesion that are inaccessible from the more common dorsal approach (DSS). Further, we propose that VSS will produce novel mechanisms of function plasticity that can amplify recovery when combined with DSS. To test this hypothesis, we propose the following aims: Aim 1: Determine acute molecular and physiological mechanisms of VSS when applied to subacute cervical spinal cord injury. Aim 2: Establish the functional impact of site of stimulation and rehabilitative training on recovery from early chronic cervical spinal cord injury. Aim 3: Establish the synergistic effects of combined VSS and DSS after cervical spinal cord injury. These studies will explore an exciting new approach to promote neural recovery of the upper limb, an area of research that has had limited investigation, but remains a primary concern for the patient. Our approach will rigorously establish the physiological and functional effects of the site of stimulation on the molecular and physiological mechanisms of upper limb plasticity.


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 = $445,467 )
2026	2026	THE METHODIST HOSPITAL RESEARCH INSTITUTE	6565 FANNIN ST STE D200	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	8/24/2026	NON-COMPETING CONTINUATION	$445,467
														Subtotal = $445,467

Issue Date FY: 2025 ( Subtotal = $445,467 )
2025	2025	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/7/2025	NON-COMPETING CONTINUATION	$445,467
														Subtotal = $445,467

Issue Date FY: 2024 ( Subtotal = $455,365 )
2024	2024	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	9/6/2024	NON-COMPETING CONTINUATION	$455,365
														Subtotal = $455,365

Issue Date FY: 2023 ( Subtotal = $469,448 )
2023	2023	METHODIST HOSPITAL, THE	6670 BERTNER AVE	HOUSTON	TX	77030	HARRIS	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/20/2023	NEW	$469,448
														Subtotal = $469,448

Grand Total All Awards = $1,815,747

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Spinal Neuromodulation to Promote Physiologic and Molecular Plasticity in theInjured Spinal Cord

Award Number: R01NS132123

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: 09/20/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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