Time and frequency domain analysis of physiological features during autonomic dysreflexia after spinal cord injury.

Introduction: Autonomic dysreflexia (AD) affects about 70% of individuals with spinal cord injury (SCI) and can have severe consequences, including death if not promptly detected and managed. The current gold standard for AD detection involves continuous blood pressure monitoring, which can be inconvenient. Therefore, a non-invasive detection device would be valuable for rapid and continuous AD detection. Methods: Implanted rodent models were used to analyze autonomic dysreflexia after spinal cord injury. Skin nerve activity (SKNA) features were extracted from ECG signals recorded non-invasively, using ECG electrodes. At the same time, blood pressure and ECG data sampled was collected using an implanted telemetry device. Heart rate variability (HRV) features were extracted from these ECG signals. SKNA and HRV parameters were analyzed in both the time and frequency domain. Results: We found that SKNA features showed an increase approximately 18 seconds before the typical rise in systolic blood pressure, indicating the onset of AD in a rat model with upper thoracic SCI. Additionally, low-frequency components of SKNA in the frequency domain were dominant during AD, suggesting their potential inclusion in an AD detection system for improved accuracy. Discussion: Utilizing SKNA measurements could enable early alerts to individuals with SCI, allowing timely intervention and mitigation of the adverse effects of AD, thereby enhancing their overall well-being and safety.

Acclimation Protocol to Minimize Stress in Immobilized Rats During Non-Invasive Multimodal Sensing of the Autonomic Nervous System.

INTRODUCTION: Rodent models are often used in spinal cord injury investigations to measure physiological parameters but require rats to be restrained during data collection to prevent motion and stress-induced artifacts. MATERIALS AND METHODS: A 4-week acclimation protocol was developed to reduce sympathetic activity during experimentation to collect clean data. Physiological parameters were analyzed throughout the acclimation protocol using surface-based electrodes and an implanted sensor. The sensor was used to extract systolic blood pressure, skin nerve activity, and heart rate variability parameters. RESULTS: Our protocol exposed a minimal increase in sympathetic activity during experimentation despite long periods of restraint. The data suggest that the acclimation protocol presented successfully minimized changes in physiological parameters because of prolonged restraint. CONCLUSIONS: This is necessary to ensure that physiological recordings are not affected by undue stress because of the process of wearing the sensor. This is important when determining the effects of stress when studying dysautonomia after spinal cord injury, Parkinson's disease, and other neurological disorders.

OPA1 deletion in brown adipose tissue improves thermoregulation and systemic metabolism via FGF21.

Adrenergic stimulation of brown adipocytes alters mitochondrial dynamics, including the mitochondrial fusion protein optic atrophy 1 (OPA1). However, direct mechanisms linking OPA1 to brown adipose tissue (BAT) physiology are incompletely understood. We utilized a mouse model of selective OPA1 deletion in BAT (OPA1 BAT KO) to investigate the role of OPA1 in thermogenesis. OPA1 is required for cold-induced activation of thermogenic genes in BAT. Unexpectedly, OPA1 deficiency induced fibroblast growth factor 21 (FGF21) as a BATokine in an activating transcription factor 4 (ATF4)-dependent manner. BAT-derived FGF21 mediates an adaptive response by inducing browning of white adipose tissue, increasing resting metabolic rates, and improving thermoregulation. However, mechanisms independent of FGF21, but dependent on ATF4 induction, promote resistance to diet-induced obesity in OPA1 BAT KO mice. These findings uncover a homeostatic mechanism of BAT-mediated metabolic protection governed in part by an ATF4-FGF21 axis, which is activated independently of BAT thermogenic function.