Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Combinatorial respiratory rehabilitation approaches to enhance breathing recovery after cervical spinal cord injury

Award Number: R01NS142310
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: 06/01/2025
PERIOD OF PERFORMANCE END DATE: 04/30/2030

Group Awards By:

View Award Description

Combinatorial respiratory rehabilitation approaches to enhance breathing recovery after cervical spinal cord injury - ABSTRACT Cervical spinal cord injury (SCI) disrupts neural pathways to spinal respiratory motor neurons, causing impaired breathing and even death. New treatment strategies are desperately needed to improve breathing ability after cervical SCI. Since most SCIs are incomplete, meaningful functional recovery can be induced by harnessing the intrinsic capacity for neuroplasticity, strengthening spared neural pathways to respiratory motor neurons. Therapeutic acute intermittent hypoxia (tAIH) is a simple, safe and effective means to induce respiratory motor plasticity and improve breathing ability in rodent models of acute cervical SCI but is considerably less effective with chronic injury. However, tAIH is highly effective in non-respiratory motor systems in chronic SCI, but only when paired with task-specific training. The impact of combined tAIH and task-specific respiratory training is not known. Thus, our fundamental goal is to maximize breathing recovery after chronic, incomplete cervical SCI using a combinatorial approach that pairs tAIH with respiratory training. We propose to study two distinct respiratory training paradigms: physical exercise and exposure to elevated levels of carbon dioxide (CO2; e.g., hypercapnia). Physical exercise increases breathing via a well-known and reproducible phenomenon known as “exercise hyperpnea”, whereby breathing is increased in proportion to metabolic rate and blood gas levels are regulated by a mechanism independent of chemoreceptor feedback. On the other hand, we can elicit robust, automatic increases in breathing via hypercapnia, which may provide an opportunity for task specific training in cases where vigorous exercise is not possible (e.g., those with limited mobility). This unique form of respiratory training involves activation of carotid CO2 chemoreceptors and is well tolerated and easily administered to individuals with impaired mobility. Although the mechanisms differ, both exercise hyperpnea and hypercapnia engage neural pathways involved in automatic (vs. volitional) breathing control, thus represent forms of automatic respiratory training. We will test the hypotheses that maximal therapeutic benefits will be achieved when tAIH is paired with either treadmill- or hypercapnia-based respiratory training. We will test our working cellular model concerning mechanisms of synergy between tAIH and task- specific training, which we hypothesize converges on spinal BDNF/TrkB signaling in phrenic motor neurons. Lastly, we predict lasting changes in the neural circuits innervating phrenic motor neurons, shifting the balance of excitatory vs inhibitory inputs, and ultimately increasing their excitability and overall motor output. These are the first studies to pair tAIH with respiratory training that targets automatic respiratory control, which is critical for restoring independent breathing ability. This research will inform future clinical trials as we seek potent and enduring recovery of breathing ability after chronic SCI. Indeed, our team has a documented history of translation, and we are actively translating highly novel discoveries from preclinical models to persons with SCI. Thus, in a very real sense, our work will help accelerate translation of promising ideas into clinical practice.


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 = $444,746 )
2026	2026	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/5/2026	NON-COMPETING CONTINUATION	$444,746
														Subtotal = $444,746

Issue Date FY: 2025 ( Subtotal = $449,391 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	5/27/2025	NEW	$449,391
														Subtotal = $449,391

Grand Total All Awards = $894,137

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Combinatorial respiratory rehabilitation approaches to enhance breathing recovery after cervical spinal cord injury

Award Number: R01NS142310

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: 06/01/2025

PERIOD OF PERFORMANCE END DATE: 04/30/2030

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer