Spinal cord representation of motor cortex plasticity reflects corticospinal tract LTP

Although it is well known that activity-dependent motor cortex (MCX) plasticity produces long-term potentiation (LTP) of local cortical circuits, leading to enhanced muscle function, the effects on the corticospinal projection to spinal neurons has not yet been thoroughly studied. Here, we investigate a spinal locus for corticospinal tract (CST) plasticity in anesthetized rats using multichannel recording of motor-evoked, intraspinal local field potentials (LFPs) at the sixth cervical spinal cord segment. We produced LTP by intermittent theta burst electrical stimulation (iTBS) of the wrist area of MCX. Approximately 3 min of MCX iTBS potentiated the monosynaptic excitatory LFP recorded within the CST termination field in the dorsal horn and intermediate zone for at least 15 min after stimulation. Ventrolaterally, in the spinal cord gray matter, which is outside the CST termination field in rats, iTBS potentiated an oligosynaptic negative LFP that was localized to the wrist muscle motor pool. Spinal LTP remained robust, despite pharmacological blockade of iTBS-induced LTP within MCX using MK801, showing that activity-dependent spinal plasticity can be induced without concurrent MCX LTP. Pyramidal tract iTBS, which preferentially activates the CST, also produced significant spinal LTP, indicating the capacity for plasticity at the CST–spinal interneuron synapse. Our findings show CST monosynaptic LTP in spinal interneurons and demonstrate that spinal premotor circuits are capable of further modifying descending MCX control signals in an activity-dependent manner.

Peripheral Immune Dysfunction: A Problem of Central Importance after Spinal Cord Injury

Individuals with spinal cord injuries (SCI) exhibit increased susceptibility to infection, with pneumonia consistently ranking as a leading cause of death. Despite this statistic, chronic inflammation and concurrent immune suppression have only recently begun to be explored mechanistically. Investigators have now identified numerous changes that occur in the peripheral immune system post-SCI, including splenic atrophy, reduced circulating lymphocytes, and impaired lymphocyte function. These effects stem from maladaptive changes in the spinal cord after injury, including plasticity within the spinal sympathetic reflex circuit that results in exaggerated sympathetic output in response to peripheral stimulation below injury level. Such pathological activity is particularly evident after a severe high-level injury above thoracic spinal cord segment 6, greatly increasing the risk of the development of sympathetic hyperreflexia and subsequent disrupted regulation of lymphoid organs. Encouragingly, studies have presented evidence for promising therapies, such as modulation of neuroimmune activity, to improve regulation of peripheral immune function. In this review, we summarize recent publications examining (1) how various immune functions and populations are affected, (2) mechanisms behind SCI-induced immune dysfunction, and (3) potential interventions to improve SCI individuals’ immunological function to strengthen resistance to potentially deadly infections.

The Histopathology of Severe Graded Compression in Lower Thoracic Spinal Cord Segment of Rat, Evaluated at Late Post-injury Phase

Spontaneous recovery of lost motor functions is relative fast in rodent models after inducing a very mild/moderate spinal cord injury (SCI), and this may complicate a reliable evaluation of the effectiveness of potential therapy. Therefore, a severe graded (30 g, 40 g and 50 g) weight-compression SCI at the Th9 spinal segment, involving an acute mechanical impact followed by 15 min of persistent compression, was studied in adult female Wistar rats. Functional parameters, such as spontaneous recovery of motor hind limb and bladder emptying function, and the presence of hematuria were evaluated within 28 days of the post-traumatic period. The disruption of the blood-spinal cord barrier, measured by extravasated Evans Blue dye, was examined 24 h after the SCI, when maximum permeability occurs. At the end of the survival period, the degradation of gray and white matter associated with the formation of cystic cavities, and quantitative changes of glial structural proteins, such as GFAP, and integral components of axonal architecture, such as neurofilaments and myelin basic protein, were evaluated in the lesioned area of the spinal cord. Based on these functional and histological parameters, and taking the animal’s welfare into account, the 40 g weight can be considered as an upper limit for severe traumatic injury in this compression model.

The Muscle Activation Differences in Post-Stroke Upper Limb Flexion Synergy Based on Spinal Cord Segments: A Preliminary Proof-of-Concept Study

Objective: This study examined the activation difference of muscles innervated by cervical cord 5-6 (C5-C6) and cervical cord 8- thoracic cord 1 (C8-T1) in upper limb flexion synergy after stroke.Methods: Surface electromyography (sEMG) signals were collected during elbow flexion in stroke patients and healthy controls. The study compared normalized activation of two pairs of muscles that could cause similar joint movement but which dominated different spinal cord segments (clavicular part of the pectoralis major, PC vs. Sternocostal part of the pectoralis major, PS; Flexor carpi radialis, FCR vs. Flexor carpi ulnaris, FCU). In each muscle pair, one muscle was innervated by the same spinal cord segment (C5-C6), dominating the elbow flexion and the other was not. The comparison of the activation of the same muscle between patients and healthy controls was undertaken after standardization based on the activation of the biceps brachii in elbow flexion.Results: There was no difference between the PC and PS's normalized activation in healthy controls while the PC's normalized activation was higher than PS in stroke patients during elbow flexion. Similarly, there was no significant difference in normalized activation between FCR and FCU in healthy controls, and the same is true for stroke patients. However, the standardized activation of both FCR and FCU in stroke patients was significantly lower than that in healthy controls.Conclusion: After stroke, the activation of the distal muscles of the upper limb decreased significantly regardless of the difference of spinal cord segments; while the activation of the proximal muscles innervated by the same spinal cord segment (C5-C6) dominating the elbow flexion showed higher activation during flexion synergy. The difference in muscle activation based on spinal cord segments may be the reason for the stereotyped joint movement of upper limb flexion synergy.

Changes of Dorsal Root Ganglion Volume in Dogs with Clinical Signs of Degenerative Myelopathy Detected by Water-Excitation Magnetic Resonance Imaging

Canine degenerative myelopathy (DM) is a progressive and fatal neurodegenerative disease. However, a definitive diagnosis of DM can only be achieved by postmortem histopathological examination of the spinal cord. The purpose of this study was to investigate whether the volumetry of DRG using the ability of water-excitation magnetic resonance imaging (MRI) to visualize the DRG in dogs has premortem diagnostic value for DM. Eight dogs with DM, twenty-four dogs with intervertebral disc herniation (IVDH), and eight control dogs were scanned using a 3.0-tesla MRI system, and water-excitation images were obtained to visualize and measure the volume of DRG, normalized by body surface area. The normalized mean DRG volume between each spinal cord segment and mean volume of all DRG between T8 and L2 in the DM group was significantly lower than that in the control and the IVDH groups (P = 0.011, P = 0.002, respectively). There were no correlations within the normalized mean DRG volume between DM stage 1 and stage 4 (rs = 0.312, P = 0.128, respectively). In conclusion, DRG volumetry by the water-excitation MRI provides a non-invasive and quantitative assessment of neurodegeneration in DRG and may have diagnostic potential for DM.

Postdecompressive spinal cord blood flow increments in a cervical chronic myelopathy model in rats

OBJECTIVE In cervical spondylotic myelopathy (CSM), compromise of blood flow to the compressed spinal cord has been postulated to contribute to the development of myelopathy. Although decompressive surgery has been considered to improve spinal cord blood flow, evidence to support this notion is scarce. To determine whether blood flow improves after decompressive surgery for CSM, regional blood flow was measured in a model of chronic cervical compression in rats by using a fluorescent microsphere technique. METHODS Thin polyurethane sheets, measuring precisely 3 × 5 × 0.7 mm, were implanted under the C5–6 laminae in 24 rats to induce continuous compression on the cervical spinal cord. These sheets expand gradually by absorbing tissue fluid. This animal model has been demonstrated to reproduce the clinical features and histological changes of CSM, including progressive motor weakness with delayed onset and insidious tissue damage prior to symptom onset. Twenty-four rats that underwent sham operation were allocated to a control group. To confirm the development of cervical myelopathy, motor functions were measured weekly over the study period. Nine weeks after implantation of the sublaminar expanding sheets, histological studies and C5–6 decompressive surgery were conducted. Regional blood flow in the brainstem and cervical spinal cord was measured sequentially until 120 minutes after decompression. RESULTS In the CSM group, bilateral forepaw grip strength deteriorated progressively from 5 weeks after implantation. In the compressed C5–6 segment of the spinal cord, significant flattening of the cord, a decreased number of motor neurons, and vacuolations of gray matter were demonstrated. In the control group, blood flow in the brainstem and cervical spinal cord was unchanged by the decompressive surgery. In the CSM group, however, diminished blood flow and continuous blood flow increments for 120 minutes after decompression were demonstrated in the compressed C5–6 spinal cord segment. CONCLUSIONS Chronic mechanical compression induced regional spinal cord blood flow insufficiency concomitant with progressive neuronal loss and motor dysfunction in a chronic compression model in rats. Decompressive surgery increased spinal cord blood flow. These findings suggest that blood flow recovery may contribute to postoperative neurological improvement.

Closed spinal dysraphism in a 6-month-old mixed breed dog

The term spinal dysraphism defines an incomplete fusion or a bone defect that affects the neural structures of the spinal cord due to a neural tube malformation. A 6-month-old, male, mixed-breed dog, was evaluated for paraparesis, pelvic limb proprioceptive ataxia, faecal and urinary incontinence. A neurological examination indicated an L4-S3 spinal cord segment lesion. A thoracolumbar and lumbosacral spine magnetic resonance imaging was performed and a closed spinal dysraphism, with the presence of a lipomyelomeningocele, was detected. The magnetic resonance imaging showed an entire narrowing passage and a fibrous mass stemming from a wedge-shaped gap in the caudal region of the dorsal lamina of the L4 vertebra, leaving the spinal canal towards the skin surface in the region where the skin stigma was observed. A dorsal laminectomy was performed, the spinal cord was exposed, and the entire fibrous mass was excised. Three months postoperatively, the patient had a complete resolution of the urinary and faecal incontinence showing only a residual mild paraparesis, which remained six months after surgery. The surgical procedure resulted in the satisfactory recovery of the neurological signs.

Acute transverse myelitis after inactivated COVID-19 vaccine

Vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been rapidly developed to prevent coronavirus disease 2019 (COVID-19) pandemic. There is increasing safety concerns regarding COVID-19 vaccines. We report a 78-year old woman who was presented with tetraparesis, paresthesias of bilateral upper extremities, and urinary retention of one-day duration. Three weeks before these symptoms, she was vaccinated with CoronaVAC vaccine (Sinovac Life Sciences, China). Spine magnetic resonance imaging showed longitudinally extensive transverse myelitis (TM) from the C1 to the T3 spinal cord segment. An extensive diagnostic workup was performed to exclude other possible causes of TM. We suggest that longitudinally extensive TM may be associated with COVID-19 vaccination in this case. To the best of our knowledge, this is the first report of longitudinally extensive TM developing after CoronaVac vaccination. Clinicians should be aware of neurological symptoms after vaccination of COVID-19.

EA Improves the Motor Function in Rats with Spinal Cord Injury by Inhibiting Signal Transduction of Semaphorin3A and Upregulating of the Peripheral Nerve Networks

Peripheral nerve networks (PNNs) play a vital role in the neural recovery after spinal cord injury (SCI). Electroacupuncture (EA), as an alternative medicine, has been widely used in SCI and was proven to be effective on neural functional recovery. In this study, the interaction between PNNs and semaphrin3A (Sema3A) in the recovery of the motor function after SCI was observed, and the effect of EA on them was evaluated. After the establishment of the SCI animal model, we found that motor neurons in the ventral horn of the injured spinal cord segment decreased, Nissl bodies were blurry, and PNNs and Sema3A as well as its receptor neuropilin1 (NRP1) aggregated around the central tube of the gray matter of the spinal cord. When we knocked down the expression of Sema3A at the damage site, NRP1 also downregulated, importantly, PNNs concentration decreased, and tenascin-R (TN-R) and aggrecan were also reduced, while the Basso-Beattie-Bresnahan (BBB) motor function score dramatically increased. In addition, when conducting EA stimulation on Jiaji (EX-B2) acupoints, the highly upregulated Sema3A and NRP1 were reversed post-SCI, which can lessen the accumulation of PNNs around the central tube of the spinal cord gray matter, and simultaneously promote the recovery of motor function in rats. These results suggest that EA may further affect the plasticity of PNNs by regulating the Sema3A signal and promoting the recovery of the motor function post-SCI.