Neuroplasticity of Sympathetic and Serotonergic Pathways to Improve the Recovery of Cardiovascular Activity after Spinal Cord Injury
Abstract
Spinal cord injuries (SCI) can severely impair bodily function, making early intervention crucial for recovery and preventing further damage. Injuries at or above the sixth thoracic (T6) vertebra impair neural cardiovascular regulation, leading to bradycardia, reduced blood flow, and hypotension. This is important because early intervention and participation in physical therapy are critical for recovery of motor function after SCI, and impaired cardiovascular regulation limits participation. Brainstem regions, including the raphe nuclei, contain serotonergic neurons with axons that project to the spinal cord and release serotonin (5-HT), a neurotransmitter essential for regulating heart rate, blood pressure, and motor control. SCI disrupts descending pathways, reducing 5-HT availability below the injury site. Because 5-HT regulates spinal neuronal excitability and promotes neuroplasticity, restoration of 5-HT pathways around the injury site can improve SCI recovery. Our study aims to investigate the effect of stimulating sympathetic preganglionic neurons, essential in cardiovascular regulation and signaling, on recovery after SCI. To determine the technique that best identifies preganglionic sympathetic neurons, we used immunohistochemistry (IHC) to compare Fluoro-Gold neuronal identification with Choline Acetyl Transferase (ChAT), a marker for sympathetic preganglionic neurons. We then validated 5-HT IHC to determine the extent of recovery after stimulation of sympathetic preganglionic neurons. To exclusively stimulate sympathetic neurons, we generated a transgenic rat model (ChAT-cre) that expresses cre recombinase enzyme within only ChAT-expressing neurons. We then injected a retrograde viral vector (pAAV-hSyn-DIO-hM3D(Gq)-mCherry) containing floxed designer receptors exclusively activated by designer drugs (DREADDs) into the adrenal gland to chemogenetically stimulate sympathetic preganglionic neurons after SCI. Studies will be conducted to optimize the dose of chemogenetic stimulant and the effect of chronic stimulation on spinal 5-HT neuroplasticity. These findings will provide insights into neuroplasticity after SCI and help develop targeted therapies to improve recovery of cardiovascular regulation and quality of life after SCI.
Start Time
16-4-2025 1:30 PM
End Time
16-4-2025 4:00 PM
Presentation Type
Poster
Presentation Category
Health
Student Type
Undergraduate Student
Faculty Mentor
Matthew Zahner
Faculty Department
Biomedical Health Sciences
Neuroplasticity of Sympathetic and Serotonergic Pathways to Improve the Recovery of Cardiovascular Activity after Spinal Cord Injury
Spinal cord injuries (SCI) can severely impair bodily function, making early intervention crucial for recovery and preventing further damage. Injuries at or above the sixth thoracic (T6) vertebra impair neural cardiovascular regulation, leading to bradycardia, reduced blood flow, and hypotension. This is important because early intervention and participation in physical therapy are critical for recovery of motor function after SCI, and impaired cardiovascular regulation limits participation. Brainstem regions, including the raphe nuclei, contain serotonergic neurons with axons that project to the spinal cord and release serotonin (5-HT), a neurotransmitter essential for regulating heart rate, blood pressure, and motor control. SCI disrupts descending pathways, reducing 5-HT availability below the injury site. Because 5-HT regulates spinal neuronal excitability and promotes neuroplasticity, restoration of 5-HT pathways around the injury site can improve SCI recovery. Our study aims to investigate the effect of stimulating sympathetic preganglionic neurons, essential in cardiovascular regulation and signaling, on recovery after SCI. To determine the technique that best identifies preganglionic sympathetic neurons, we used immunohistochemistry (IHC) to compare Fluoro-Gold neuronal identification with Choline Acetyl Transferase (ChAT), a marker for sympathetic preganglionic neurons. We then validated 5-HT IHC to determine the extent of recovery after stimulation of sympathetic preganglionic neurons. To exclusively stimulate sympathetic neurons, we generated a transgenic rat model (ChAT-cre) that expresses cre recombinase enzyme within only ChAT-expressing neurons. We then injected a retrograde viral vector (pAAV-hSyn-DIO-hM3D(Gq)-mCherry) containing floxed designer receptors exclusively activated by designer drugs (DREADDs) into the adrenal gland to chemogenetically stimulate sympathetic preganglionic neurons after SCI. Studies will be conducted to optimize the dose of chemogenetic stimulant and the effect of chronic stimulation on spinal 5-HT neuroplasticity. These findings will provide insights into neuroplasticity after SCI and help develop targeted therapies to improve recovery of cardiovascular regulation and quality of life after SCI.