Spinal projecting neurons in rostral ventromedial medulla co-regulate motor and sympathetic tone.

Many behaviors require the coordinated actions of somatic and autonomic functions. However, the underlying mechanisms remain elusive. By opto-stimulating different populations of descending spinal projecting neurons (SPNs) in anesthetized mice, we show that stimulation of excitatory SPNs in the rostral ventromedial medulla (rVMM) resulted in a simultaneous increase in somatomotor and sympathetic activities. Conversely, opto-stimulation of rVMM inhibitory SPNs decreased both activities. Anatomically, these SPNs innervate both sympathetic preganglionic neurons and motor-related regions in the spinal cord. Fiber-photometry recording indicated that the activities of rVMM SPNs correlate with different levels of muscle and sympathetic tone during distinct arousal states. Inhibiting rVMM excitatory SPNs reduced basal muscle and sympathetic tone, impairing locomotion initiation and high-speed performance. In contrast, silencing the inhibitory population abolished muscle atonia and sympathetic hypoactivity during rapid eye movement (REM) sleep. Together, these results identify rVMM SPNs as descending spinal projecting pathways controlling the tone of both the somatomotor and sympathetic systems.

Promoting community engagement in spinal cord injury research: a case example.

Community engagement is an important method of knowledge translation in spinal cord injury (SCI) research where researchers collaborate with people with lived experience, care partners, and other research users to improve the quality of research. This perspective article aims to promote community engagement in SCI research by describing useful resources for its implementation and providing an example project using the North American Spinal Cord Injury Consortium (NASCIC) process for such partnerships. Researchers from the Jefferson College of Rehabilitation Sciences' (JCRS) Center for Outcomes and Measurement engaged NASCIC to create an advisory committee composed of four people living with SCI to make recommendations for the methods of a large-scale study to develop a clinical outcome assessment. The advisory committee made usable recommendations for enhancing recruitment methods and reducing burden and barriers to participation. The successful partnership between NASCIC and JCRS shows the feasibility and value of SCI community engagement in research.

Challenges in Contemporary Spine Surgery: A Comprehensive Review of Surgical, Technological, and Patient-Specific Issues.

Spine surgery has significantly progressed due to innovations in surgical techniques, technology, and a deeper understanding of spinal pathology. However, numerous challenges persist, complicating successful outcomes. Anatomical intricacies at transitional junctions demand precise surgical expertise to avoid complications. Technical challenges, such as underestimation of the density of fixed vertebrae, individual vertebral characteristics, and the angle of pedicle inclination, pose additional risks during surgery. Patient anatomical variability and prior surgeries add layers of difficulty, often necessitating thorough pre- and intraoperative planning. Technological challenges involve the integration of artificial intelligence (AI) and advanced visualization systems. AI offers predictive capabilities but is limited by the need for large, high-quality datasets and the "black box" nature of machine learning models, which complicates clinical decision making. Visualization technologies like augmented reality and robotic surgery enhance precision but come with operational and cost-related hurdles. Patient-specific challenges include managing postoperative complications such as adjacent segment disease, hardware failure, and neurological deficits. Effective patient outcome measurement is critical, yet existing metrics often fail to capture the full scope of patient experiences. Proper patient selection for procedures is essential to minimize risks and improve outcomes, but criteria can be inconsistent and complex. There is the need for continued technological innovation, improved patient-specific outcome measures, and enhanced surgical education through simulation-based training. Integrating AI in preoperative planning and developing comprehensive databases for spinal pathologies can aid in creating more accurate, generalizable models. A holistic approach that combines technological advancements with personalized patient care and ongoing education is essential for addressing these challenges and improving spine surgery outcomes.

Imaging demyelinated axons after spinal cord injuries with PET tracer [ 18 F]3F4AP.

Spinal cord injuries (SCI) often lead to lifelong disability. Among the various types of injuries, incomplete and discomplete injuries, where some axons remain intact, offer potential for recovery. However, demyelination of these spared axons can worsen disability. Demyelination is a reversible phenomenon, and drugs like 4-aminopyridine (4AP), which target K+ channels in demyelinated axons, show that conduction can be restored. Yet, accurately assessing and monitoring demyelination post-SCI remains challenging due to the lack of suitable imaging methods. In this study, we introduce a novel approach utilizing the positron emission tomography (PET) tracer, [ 18 F]3F4AP, specifically targeting K+ channels in demyelinated axons for SCI imaging. Rats with incomplete contusion injuries were imaged up to one month post-injury, revealing [ 18 F]3F4AP's exceptional sensitivity to injury and its ability to detect temporal changes. Further validation through autoradiography and immunohistochemistry confirmed [ 18 F]3F4AP's targeting of demyelinated axons. In a proof-of-concept study involving human subjects, [ 18 F]3F4AP differentiated between a severe and a largely recovered incomplete injury, indicating axonal loss and demyelination, respectively. Moreover, alterations in tracer delivery were evident on dynamic PET images, suggestive of differences in spinal cord blood flow between the injuries. In conclusion, [ 18 F]3F4AP demonstrates efficacy in detecting incomplete SCI in both animal models and humans. The potential for monitoring post-SCI demyelination changes and response to therapy underscores the utility of [ 18 F]3F4AP in advancing our understanding and management of spinal cord injuries.