Restoring Blood Pressure Post-Spinal Cord Injury Utilizing a Chemogenetic Approach
Abstract
Traumatic spinal cord injury (SCI) produces profound autonomic cardiovascular dysfunction that can prevent full participation in rehabilitation. A major clinical barrier is orthostatic hypotension, which occurs when brain stem sympathetic neurons within the rostroventrolateral medulla (RVLM) are unable to communicate with spinal sympathetic preganglionic neurons (SPNs) below the injury site. Reduced SPN activity allows venous pooling in the lower extremities and can cause dizziness upon postural change. Although spinal electrical stimulation can improve orthostatic tolerance after SCI, the cellular and circuit mechanisms responsible for these benefits remain poorly defined. It is unclear whether stimulation improves cardiovascular control by directly activating SPNs or indirectly by recruiting propriospinal networks that synapse onto SPNs. We hypothesize that chemogenetic stimulation of SPNs after SCI will improve the recovery of sympathetic regulation of blood pressure. To do this, we used a novel approach to selectively stimulate SPNs via a viral vector (retro-DIO-CAG-hM3Dq-mCherry) containing Designer Receptor Exclusively Activated by Designer Drugs (DREADDs) to infect the thoracic spinal cord of transgenic Long Evans ChAT::Cre rats via injection. This limits expression of the DREADDs to SPNs that express the Cre recombinase enzyme driven by the choline acetyl transferase promoter. After infection and three weeks for transfection, the tissue was processed for immunofluorescence to assess labeling and colocalization with ChAT+ SPNs. The virus produced clear, unilateral labeling localized to the ipsilateral sympathetic region of the spinal cord, demonstrating that the injection route provides reliable access to SPNs. Next, we will activate DREADDs using clozapine-N-oxide and quantify cardiovascular effects with radiotelemetry-based measurements of arterial pressure in SCI and control rats. This platform will enable mechanistic tests of whether selective SPN activation can restore cardiovascular stability and will help distinguish direct SPN recruitment from indirect circuit-mediated effects after SCI.
Start Time
15-4-2026 9:00 AM
End Time
15-4-2026 12:00 PM
Room Number
Culp Ballroom 316
Poster Number
24
Presentation Type
Poster
Presentation Subtype
Posters - Competitive
Presentation Category
Health
Student Type
Undergraduate Student
Faculty Mentor
Matthew Zahner
Restoring Blood Pressure Post-Spinal Cord Injury Utilizing a Chemogenetic Approach
Culp Ballroom 316
Traumatic spinal cord injury (SCI) produces profound autonomic cardiovascular dysfunction that can prevent full participation in rehabilitation. A major clinical barrier is orthostatic hypotension, which occurs when brain stem sympathetic neurons within the rostroventrolateral medulla (RVLM) are unable to communicate with spinal sympathetic preganglionic neurons (SPNs) below the injury site. Reduced SPN activity allows venous pooling in the lower extremities and can cause dizziness upon postural change. Although spinal electrical stimulation can improve orthostatic tolerance after SCI, the cellular and circuit mechanisms responsible for these benefits remain poorly defined. It is unclear whether stimulation improves cardiovascular control by directly activating SPNs or indirectly by recruiting propriospinal networks that synapse onto SPNs. We hypothesize that chemogenetic stimulation of SPNs after SCI will improve the recovery of sympathetic regulation of blood pressure. To do this, we used a novel approach to selectively stimulate SPNs via a viral vector (retro-DIO-CAG-hM3Dq-mCherry) containing Designer Receptor Exclusively Activated by Designer Drugs (DREADDs) to infect the thoracic spinal cord of transgenic Long Evans ChAT::Cre rats via injection. This limits expression of the DREADDs to SPNs that express the Cre recombinase enzyme driven by the choline acetyl transferase promoter. After infection and three weeks for transfection, the tissue was processed for immunofluorescence to assess labeling and colocalization with ChAT+ SPNs. The virus produced clear, unilateral labeling localized to the ipsilateral sympathetic region of the spinal cord, demonstrating that the injection route provides reliable access to SPNs. Next, we will activate DREADDs using clozapine-N-oxide and quantify cardiovascular effects with radiotelemetry-based measurements of arterial pressure in SCI and control rats. This platform will enable mechanistic tests of whether selective SPN activation can restore cardiovascular stability and will help distinguish direct SPN recruitment from indirect circuit-mediated effects after SCI.
