Spinal Cord In Humans Research Articles

Electrophysiology Methods for Assessing of Neurodegenerative and Post-Traumatic Processes as Applied to Translational Research.

Electrophysiological studies have long established themselves as reliable methods for assessing the functional state of the brain and spinal cord, the degree of neurodegeneration, and evaluating the effectiveness of therapy. In addition, they can be used to diagnose, predict functional outcomes, and test the effectiveness of therapeutic and rehabilitation programs not only in clinical settings, but also at the preclinical level. Considering the urgent need to develop potential stimulators of neuroregeneration, it seems relevant to obtain objective data when modeling neurological diseases in animals. Thus, in the context of the application of electrophysiological methods, not only the comparison of the basic characteristics of bioelectrical activity of the brain and spinal cord in humans and animals, but also their changes against the background of neurodegenerative and post-traumatic processes are of particular importance. In light of the above, this review will contribute to a better understanding of the results of electrophysiological assessment in neurodegenerative and post-traumatic processes as well as the possibility of translating these methods from model animals to humans.

Current strategies for regenerative therapy of spinal cord injury

Spinal cord injury (SCI) is a leading cause of death and severe disability amongst young people. The incidence of SCI is 0.6–1.0 per 10,000 individuals. Unfortunately, there are no effective methods of restoring locomotor function for individuals with severe SCI. To address this issue, exoskeleton technology controlled using BCI is actively being developed for prosthetic locomotion. Despite the lack of encouraging data for severe spinal cord injuries, regenerative technologies continue to hold promise for spinal cord repair. The limited options for regenerating the central nervous system in humans necessitate creating new sources of neural stem cells for regeneration. Reprogramming autologous somatic cells neurologically can effectively serve as such a source [1]. Nevertheless, the constitution of neuroglial progenitors, which are necessary for regenerating damaged axons of the pyramidal tract, still requires clarification [2]. Some interesting efforts are underway to directly reprogram glial cells in situ using a variety of biotechnological approaches [3]. Overcoming or preventing the formation of a harsh scar tissue at the injury site is the key obstacle to successful regeneration therapy for SCI. Various scaffolds are being developed to facilitate axon regeneration, and several gene therapy agents are being tested to either knock down scar formation factors or activate extracellular matrix remodeling and reparative regeneration. Neuromodulation shows promise for SCI treatment. Studies indicate that epidural stimulation of the L2-S1 spinal cord in humans and mammals activates SPG neurons, aiding spinal walking generator functions. A potentially successful treatment approach involves scaffolds with reprogrammed cells and neuromodulation [4].

Encephalic meningioangiomatosis in a dog with high-grade undefined glioma

Meningioangiomatosis (MA) is a rare proliferative meningovascular disorder that affects mainly the cerebral cortex, brainstem and spinal cord of humans and animals and can coexist with other proliferative disorders. A 7.5-year-old male Brazilian Campeiro Bulldog died after a convulsive crisis and cardiorespiratory arrest. At necropsy, a firm, white mass involving the piriform and right occipital lobes was seen. Histologically, the mass consisted of two morphologically distinct entities that collided: a congenital malformation characterized by a proliferation of meningothelial cells around blood vessels, within the perivascular spaces; and a neoplasm composed of two cell populations with astrocytic and oligodendrocytic differentiation. Meningothelial cells and neoplastic glial cells immunolabelled for vimentin. This first reported case of encephalic MA with a high-grade undefined glioma in a dog was confirmed through clinical signs, pathological and immunohistochemical findings.

Improving Efficiency of Direct Pro-Neural Reprogramming: Much-Needed Aid for Neuroregeneration in Spinal Cord Injury.

Spinal cord injury (SCI) is a medical condition affecting ~2.5-4 million people worldwide. The conventional therapy for SCI fails to restore the lost spinal cord functions; thus, novel therapies are needed. Recent breakthroughs in stem cell biology and cell reprogramming revolutionized the field. Of them, the use of neural progenitor cells (NPCs) directly reprogrammed from non-neuronal somatic cells without transitioning through a pluripotent state is a particularly attractive strategy. This allows to "scale up" NPCs in vitro and, via their transplantation to the lesion area, partially compensate for the limited regenerative plasticity of the adult spinal cord in humans. As recently demonstrated in non-human primates, implanted NPCs contribute to the functional improvement of the spinal cord after injury, and works in other animal models of SCI also confirm their therapeutic value. However, direct reprogramming still remains a challenge in many aspects; one of them is low efficiency, which prevents it from finding its place in clinics yet. In this review, we describe new insights that recent works brought to the field, such as novel targets (mitochondria, nucleoli, G-quadruplexes, and others), tools, and approaches (mechanotransduction and electrical stimulation) for direct pro-neural reprogramming, including potential ones yet to be tested.

A critical reappraisal of corticospinal tract somatotopy and its role in traumatic cervical spinal cord syndromes.

The corticospinal tract (CST) is the preeminent voluntary motor pathway that controls human movements. Consequently, long-standing interest has focused on CST location and function in order to understand both loss and recovery of neurological function after incomplete cervical spinal cord injury, such as traumatic central cord syndrome. The hallmark clinical finding is paresis of the hands and upper-extremity function with retention of lower-extremity movements, which has been attributed to injury and the sparing of specific CST fibers. In contrast to historical concepts that proposed somatotopic (laminar) CST organization, the current narrative summarizes the accumulated evidence that 1) there is no somatotopic organization of the corticospinal tract within the spinal cord in humans and 2) the CST is critically important for hand function. The evidence includes data from 1) tract-tracing studies of the central nervous system and in vivo MRI studies of both humans and nonhuman primates, 2) selective ablative studies of the CST in primates, 3) evolutionary assessments of the CST in mammals, and 4) neuropathological examinations of patients after incomplete cervical spinal cord injury involving the CST and prominent arm and hand dysfunction. Acute traumatic central cord syndrome is characterized by prominent upper-extremity dysfunction, which has been falsely predicated on pinpoint injury to an assumed CST layer that specifically innervates the hand muscles. Given the evidence surveyed herein, the pathophysiological mechanism is most likely related to diffuse injury to the CST that plays a critically important role in hand function.

A preliminary safety assessment of vertebral augmentation with 32P brachytherapy bone cement

Comprehensive treatment for vertebral metastatic lesions commonly involves vertebral augmentation (vertebroplasty or kyphoplasty) to relieve pain and stabilize the spine followed by multiple sessions of radiotherapy. We propose to combine vertebral augmentation and radiotherapy into a single treatment by adding 32P, a β-emitting radionuclide, to bone cement, thereby enabling spinal brachytherapy to be performed without irradiating the spinal cord. The goal of this study was to address key dosimetry and safety questions prior to performing extensive animal studies. The 32P was in the form of hydroxyapatite powder activated by neutron bombardment in a nuclear reactor. We performed ex vivo dosimetry experiments to establish criteria for safe placement of the cement within the sheep vertebral body. In an in vivo study, we treated three control ewes and three experimental ewes with brachytherapy cement containing 2.23–3.03 mCi 32P ml−1 to identify the preferred surgical approach, to determine if 32P leaches from the cement and into the blood, urine, or feces, and to identify unexpected adverse effects. Our ex vivo experiments showed that cement with 4 mCi 32P ml−1 could be safely implanted in the vertebral body if the cement surface is at least 4 mm from the spinal cord in sheep and 5 mm from the spinal cord in humans. In vivo, a lateral retroperitoneal surgical approach, ventral to the transverse processes, was identified as easy to perform while allowing a safe distance to the spinal cord. The blood, urine, and feces of the sheep did not contain detectable levels of 32P, and the sheep did not experience any neurologic or other adverse effects from the brachytherapy cement. These results demonstrate, on a preliminary level, the relative safety of this brachytherapy cement and support additional development and testing.

Motavkin Scientific School

Remembrance of the outstanding scientist Professor P.A. Motavkin is largely connected with the creation of the famous neuromorphological school in Vladivostok. During a relatively short historical period, scientific discoveries were made under the leadership of P.A. Motavkin. New ideas about the mechanisms of vascular regulation of the brain and spinal cord of humans and animals were presented on the basis of these discoveries. Extensive factual material accumulated over the years of research has allowed not only to identify the basic laws of the functioning of this regulatory system in normal conditions of life, but also to solve a number of problems related to the correction of its disorders in case of vascular diseases.

Translational PET Imaging of Spinal Cord Injury with the Serotonin Transporter Tracer [11C]AFM.

The descending raphespinal serotonin (5-HT) system contributes to neural activities required for locomotion. The presynaptic serotonin transporter (SERT) is a marker of 5-HT innervation. In this study, we explored the use of PET imaging with the SERT radioligand [11C]AFM as a biomarker of 5-HT axon damage after spinal cord injury (SCI) in a rodent model and its translation to imaging SCI in humans. PET imaging with [11C]AFM was performed in healthy rats under baseline and citalopram blocking conditions and a mid-thoracic transection rat model of SCI. The lumbar-to-cervical activity (L/C) ratio was calculated for the healthy and SCI animals to assess SERT binding decrease after SCI. Finally, translation of [11C]AFM PET was attempted to explore its potential to image SCI in humans. Intense uptake in the brain and intact spinal cord was observed at 30-60min post-injection of [11C]AFM in healthy rats. About 65% of [11C]AFM uptake in the spinal cord was blocked by citalopram. In the SCI rat model, the cervical uptake of [11C]AFM was similar to that in healthy rats, but the lumbar uptake was dramatically reduced, resulting in about half the L/C ratio in SCI rats compared to healthy rats. In contrast, [11C]AFM uptake in the human spinal cord showed no obvious decrease after treatment with citalopram. In the human subjects with SCI, decreases in [11C]AFM uptake were also not obvious in the section of spinal cord caudal to the injury point. [11C]AFM PET imaging of SERT provides a useful preclinical method to non-invasively visualize the rodent spinal cord and detect SERT changes in SCI rodent models. However, there appears to be little detectable specific binding signal for [11C]AFM in the human spinal cord. An SERT tracer with higher affinity and lower non-specific binding signal is needed to image the spinal cord in humans and to assess the axonal status in SCI patients.

Magnetic resonance imaging in dogs with neuroangiostrongyliasis (rat lungworm disease).

The magnetic resonance imaging (MRI) appearance of the brain and spinal cord in humans with neuroangiostrongyliasis (NA) due to Angiostrongylus cantonensis infection has been well reported. Equivalent studies in animals are lacking. This case series describes clinical and MRI findings in 11 dogs with presumptively or definitively diagnosed NA. MRI of the brain and/or spinal cord was performed using high-field (1.5 T) or low-field (0.25 T) scanners using various combinations of transverse, sagittal, dorsal and three-dimensional (3D) T1-weighted (T1W), transverse, sagittal and dorsal T2-weighted (T2W), T2W fluid-attenuated inversion recovery (FLAIR) and T2*-weighted (T2*W) gradient echo (GRE), dorsal T2W short tau inversion recovery (STIR) and post-gadolinium transverse, sagittal, dorsal and 3D T1W and transverse T2W FLAIR sequences. In 4/6 cases where the brain was imaged, changes consistent with diffuse meningoencephalitis were observed. Evidence of meningeal involvement was evident even when not clinically apparent. The spinal cord was imaged in 9 dogs, with evidence of meningitis and myelitis detected in regions consistent with the observed neuroanatomical localization. Pathognomonic changes of neural larva migrans, as described in some human patients with NA, were not detected. NA should be considered in the differential diagnosis of dogs with MRI evidence of focal or diffuse meningitis, myelitis and/or encephalitis, especially in areas where A. cantonensis is endemic. If not precluded by imaging findings suggestive of brain herniation, cerebrospinal fluid (CSF) collection for cytology, fluid analysis, real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) testing should be considered mandatory in such cases after the MRI studies.

Mechanisms of blood flow regulation of in the skin during stimulation of the spinal cord in humans

Changes of the blood flow in the shin skin in the case of 12 healthy subjects by laser doppler flowmetry were observed under transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz were detected. It was found that the TSCS in the area of the vertebrae T11 and L1 leads to a significant increase in skin blood flow. With a stimulus intensity of 90% of the motor threshold, the microcirculation rate increased by more than 85% relative to baseline.The results of the study show that the stimulation of blood flow in the skin by TSCS is realized mainly due to the antidromic stimulation of sensory nerve fibers. An important mediator that contributes to vasodilation and increase of cutaneous blood flow in PSCS is nitric oxide (NO), which is predominantly endothelial in origin.

Mechanisms of Blood Flow Regulation in the Skin during Stimulation of the Spinal Cord in Humans

Changes in the blood flow in the shin skin were observed by laser Doppler flowmetry after transcutaneous electrical spinal cord stimulation (TSCS) by subthreshold bipolar pulses with a frequency of 30 Hz in 12 healthy subjects. It was found that TSCS in the area of the T11 and L1 vertebrae led to a significant increase in skin blood flow. The microcirculation rate increased by more than 85% relative to the baseline at a stimulus intensity of 90% of the motor threshold. Cutaneous blood flow activization by TSCS is implemented mainly through the antidromic stimulation of sensory nerve fibers. Nitric oxide (NO) is an important mediator that contributes to vasodilation and increase in cutaneous blood flow upon TSCS. NO is predominantly of endothelial origin.

WT1-Expressing Interneurons Regulate Left-Right Alternation during Mammalian Locomotor Activity.

The basic pattern of activity underlying stepping in mammals is generated by a neural network located in the caudal spinal cord. Within this network, the specific circuitry coordinating left-right alternation has been shown to involve several groups of molecularly defined interneurons. Here we characterize a population of spinal neurons that express the Wilms' tumor 1 (WT1) gene and investigate their role during locomotor activity in mice of both sexes. We demonstrate that WT1-expressing cells are located in the ventromedial region of the spinal cord of mice and are also present in the human spinal cord. In the mouse, these cells are inhibitory, project axons to the contralateral spinal cord, terminate in close proximity to other commissural interneuron subtypes, and are essential for appropriate left-right alternation during locomotion. In addition to identifying WT1-expressing interneurons as a key component of the locomotor circuitry, this study provides insight into the manner in which several populations of molecularly defined interneurons are interconnected to generate coordinated motor activity on either side of the body during stepping.SIGNIFICANCE STATEMENT In this study, we characterize WT1-expressing spinal interneurons in mice and demonstrate that they are commissurally projecting and inhibitory. Silencing of this neuronal population during a locomotor task results in a complete breakdown of left-right alternation, whereas flexor-extensor alternation was not significantly affected. Axons of WT1 neurons are shown to terminate nearby commissural interneurons, which coordinate motoneuron activity during locomotion, and presumably regulate their activity. Finally, the WT1 gene is shown to be present in the spinal cord of humans, raising the possibility of functional homology between these species. This study not only identifies a key component of the locomotor circuitry but also begins to unravel the connectivity among the growing number of molecularly defined interneurons that comprise this neural network.

Abnormalities associated with congenital scoliosis in high-altitude geographic regions.

To assess the different characteristics of congenital scoliosis between low-altitude geographic regions and high-altitude geographic regions in Chinese population and discuss the role of hypoxia on those differences. A total of 120 patients with congenital scoliosis who underwent surgical treatment in our Hospital between January 2009 and October 2017 were identified. Complete data were reviewed, including medical records, X-ray, CT, and MRI pre-operatively. According to the patient's birthplace, they were divided into low-altitude geographic regions (low group) and high-altitude geographic regions (high group). Characteristics of vertebral deformities, rib deformities, and intra-spinal malformations in two groups were analyzed. A total of 397 segments of vertebral deformities were involved in the two groups, of which 136 were involved in high group and 261 in low group. The average segments involved were 4.5 and 2.9, respectively, in two groups. 63.3% patients in high group have rib deformities, which is significantly higher than that of low group (41.1%); and the proportion of patients with complex rib deformities in high group was also higher than that in low group (57.9% VS 24.3%). The incidence of CS associated with intra-spinal malformations in low group was 38.9%, which was similar to those reported previously; however, the incidence of that in high group was 63%, significantly higher than previous reports. Our results suggested that CS patients in high-altitude geographic regions might tend to have higher proportion and more severe of rib deformities, and also be more likely to accompany with intra-spinal malformations. So we supposed that hypoxia not only aggravated the proportion and severity of rib deformities, but also affected the development of spinal cord in humans.

Microglial dysfunction as a key pathological change in adrenomyeloneuropathy.

ObjectiveMutations in ABCD1 cause the neurodegenerative disease, adrenoleukodystrophy, which manifests as the spinal cord axonopathy adrenomyeloneuropathy (AMN) in nearly all males surviving into adulthood. Microglial dysfunction has long been implicated in pathogenesis of brain disease, but its role in the spinal cord is unclear.MethodsWe assessed spinal cord microglia in humans and mice with AMN and investigated the role of ABCD1 in microglial activity toward neuronal phagocytosis in cell culture. Because mutations in ABCD1 lead to incorporation of very‐long‐chain fatty acids into phospholipids, we separately examined the effects of lysophosphatidylcholine (LPC) upon microglia.ResultsWithin the spinal cord of humans and mice with AMN, upregulation of several phagocytosis‐related markers, such as MFGE8 and TREM2, precedes complement activation and synapse loss. Unexpectedly, this occurs in the absence of overt inflammation. LPC C26:0 added to ABCD1‐deficient microglia in culture further enhances MFGE8 expression, aggravates phagocytosis, and leads to neuronal injury. Furthermore, exposure to a MFGE8‐blocking antibody reduces phagocytic activity.InterpretationSpinal cord microglia lacking ABCD1 are primed for phagocytosis, affecting neurons within an altered metabolic milieu. Blocking phagocytosis or specific phagocytic receptors may alleviate synapse loss and axonal degeneration. Ann Neurol 2017;82:813–827

Neural Stem Cells Transplantation as a Neuroprotective Strategy for Amyotrophic Lateral Sclerosis (ALS)

Introduction Amiotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a prevalence rate of up to 7.4/100,000 and the overall risk of developing ALS over a lifetime is 1:400. Most patients die from respiratory failure following a course of progressive weakness. There is no effective therapy. Novel therapeutic strategies might be directed at replacing or repairing the damaged motor neurons; Cell therapy is emerging as a potential therapeutic option in ALS. The primary objective of our study was to verify the safety and tolerability of transplantation of human fetal neural stem cells (hNSCs) directly into the spinal cord of humans. The study was approved by the SuperiorNational Health Institute. Material and Methods 18 patients with definite ALS were recruited and treated. Patients were included if they had ALS of spinal onset with severe functional impairment of the lower limbs and mild functional impairment of the upper limbs without signs of respiratory failure. The patients were monitored by clinical evaluation which included the ALS-FRS scale, Norris score, bulbar score, and MRC strength scale. Respiratory assessment included clinical evaluation, pulmonary function tests, arterial blood gases analysis, and nocturnal cardio-respiratory monitoring. Neurophysiological assessments were made including EMG, and somatosensory evoked potentials. The neuroradiological assessment consisted of MRI of spinal cord and brain before and after Gadolinium DTA infusion. A clinical psychologist performed psychological evaluation including an interview and psychological tests. Human fetal brain tissue specimens, all derived from the forebrain, were routinely collected from fetuses at gestational ages greater than the 8th post-conceptional week. They were immediately dissected and used to generate hNSC lines under sterile conditions. Dissociation of brain tissue, primary culturing and cell propagation were performed according to the procedure described previously by Vescovi and colleagues. Six patients received hNSCs microinjections into the dorsal (T7-T9) cord tract (3 of them received unilateral hNSCs microinjection while the remaining ones received bilateral microinjections); the other twelve patients received hNSCs microinjections into the cervical (C5-C6) cord tract (3 of them received unilateral hNSCs microinjection while the remaining ones received bilateral microinjections). Results No patients manifested severe adverse events such as death, respiratory failure or permanent post-surgical neurological deficits. Minor adverse events were: intercostal pain (2 patients) which was reversible after a mean period of 3 days after surgery, arm and leg sensory dysesthesia (6 patients) which was reversible after a mean period of 6 weeks after surgery. No patient manifested bladder and bowel dysfunction, or arm and leg motor deficit. All patients showed a good acceptance of the procedure and no significant modifications of the psychological status or quality of life were observed. Conclusions Our results appear to demonstrate that the procedures of fetal stem cells transplantation into the spinal cord of humans are safe and well tolerated by ALS patients. The minimal side effects and the absence of detrimental effects on neurological function support further research in stem cell transplantation in carefully monitored patients with ALS.

Myelin and oligodendrocyte development in the canine spinal cord.

We studied the developmental pattern of oligodendrocyte differentiation and myelin formation in the fetal canine spinal cord from E40 to P0. The pattern of development matches what has been described in the spinal cord of humans, rodents, and many other species. Oligodendrocytes were first found at E40, close to the central canal, with their spread in a tangential manner to the ventral and then lateral columns. Myelin development followed the same pattern but was not seen until E46. A clear subpial zone lacking glial cells and myelin was seen in the lateral column in early development, suggesting that there may also be a radial component of migration of oligodendrocyte progenitor cells (OPCs) from a ventral site. This spatial-temporal developmental pattern seen in wild type matches a delay in myelination of the superficial tracts of the spinal cord seen in a canine myelin mutant, suggesting that the mutation prevents the distribution and differentiation of OPCs at an early, but narrow, window of time during fetal development.

A Lack of Association between Human Herpes Viridiae (HHV) and Vestibular Schwannoma: Analysis of 121 Cases

Objectives: Vestibular schwannoma (VS) is a benign tumor thatarises from the Schwann cells of the vestibular nerve. Human herpes virus (HHV) 1 and 2 have been found within the parenchyma of virtually all the organs of the body and the dorsal root ganglia of the spinal cord in humans. HHV has been shown to replicate within Schwann cells, and infection by HHV has been shown to mimic VS on magnetic resonance imaging. Others hypothesized that the likely cause of VS is HHV infection and that prior exposure to HHV-3 is a potential risk factor in VS development. Our objective wasto assess for the presence of HHV viral DNA using immunohistochemical techniques in surgically excised vestibular schwannoma samples. Methods: Tissue microarrays (TMAs) representing sporadic and NF2-associated vestibular schwannomas from 121 patients, as well as both positive and negative controls, were studied. TMA sections were immunostained-using antibodies directed against HHV-1, HHV-2, HHV-3, HHV-5, and HHV-8. Results: There was no immunohistochemically detectable HHV (HHV-1, HHV-2, HHV-3, HHV-5, HHV-8) in any of the 121 cases of sporadic or NF2 cases analyzed. Conclusions: These data offer no support for an association between HHV and the development of sporadic or NF2 associated VS in humans.

Limb compressive load does not inhibit post activation depression of soleus H-reflex in indiviudals with chronic spinal cord injury

ObjectiveWe investigated the effect of various doses of limb compressive load on soleus H-reflex amplitude and post activation depression in individuals with/without chronic SCI. We hypothesized that SCI reorganization changes the typical reflex response to an external load. MethodsTen healthy adults and 10 individuals with SCI received three doses of compressive load to the top of their knee (10%, 25%, and 50% of the body weight, BW). Soleus H-reflexes were measured before (baseline) and during the loading phase. ResultsWith persistent background muscle activity across all testing sessions, segment compressive load significantly decreased post activation depression in the control group, but did not change the post activation ratio in the SCI group. Normalized H2 amplitude significantly increased according to load (50%>25%>10%) in the control group whereas was minimally modulated to load in those with SCI. ConclusionsSegment compressive load inhibits post activation depression in humans without SCI, but minimally modulates the reflex circuitry in people with chronic SCI. These findings suggest that spinal cord reorganization mitigates the typical response to load in people with chronic SCI. SignificanceEarly limb load training may impact the reorganization of the spinal cord in humans with acute SCI.

The Importance of TM3-4 Loop Subdomains for Functional Reconstitution of Glycine Receptors by Independent Domains

Truncated glycine receptors that have been found in human patients suffering from the neuromotor disorder hyperekplexia or in spontaneous mouse models resulted in non-functional ion channels. Rescue of function experiments with the lacking protein portion expressed as a separate independent domain demonstrated restoration of glycine receptor functionality in vitro. This construct harbored most of the TM3-4 loop, TM4, and the C terminus and was required for concomitant transport of the truncated α1 and the complementation domain from the endoplasmic reticulum toward the cell surface, thereby enabling complex formation of functional glycine receptors. Here, the complementation domain was stepwise truncated from its N terminus in the TM3-4 loop. Truncation of more than 49 amino acids led again to loss of functionality in the receptor complex expressed from two independent domain constructs. We identified residues 357-418 in the intracellular TM3-4 loop as being required for reconstitution of functional glycine-gated channels. All complementation constructs showed cell surface protein expression and correct orientation according to glycine receptor topology. Moreover, we demonstrated that the truncations did not result in a decreased protein-protein interaction between both glycine receptor domains. Rather, deletions of more than 49 amino acids abolished conformational changes necessary for ion channel opening. When the TM3-4 loop subdomain harboring residues 357-418 was expressed as a third independent construct together with the truncated N-terminal and C-terminal glycine receptor domains, functionality of the glycine receptor was again restored. Thus, residues 357-418 represent an important determinant in the process of conformational rearrangements following ligand binding resulting in channel opening.

The P18 component of the median nerve SEP recorded from a posterior to anterior neck montage

ObjectiveTo investigate the P18 component in the posterior to anterior neck montage after median nerve stimulation. MethodsSomatosensory evoked potentials, through electrical wrist stimulation, were collected. In 12 subjects, the presence of the P18 component was evaluated in the posterior to anterior neck montage. In 10 subjects, the effects of simultaneous vibration of the hand were evaluated. In five subjects, responses after double-pulse stimulation (ISI 20ms) were evaluated. ResultsThe P18 component was identified in all subjects. Vibration reduced the amplitude of all components except the P18 and N18. Double-pulse stimulation reduced the amplitude of the P18 and the N18 components without significantly changing the amplitude of the other components. ConclusionsThe posterior to anterior neck montage allows for recording the P18 component. The amplitude reduction of all components during vibration, except N18 and P18, is interpreted as reflecting inhibitory activities at the cuneiform nucleus and at the segmental dorsal horn of the spinal cord, respectively. The reduction in the P18 component after double-pulse stimulation is compatible with previous observations on the positive component of cord dorsum potentials. SignificanceStudying this component may add to the knowledge of the function of the spinal cord in humans.