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BACKGROUND: There is a growing interest in the use of technology in the field of neurorehabilitation in order to quantify and generate knowledge about sensorimotor disorders after neurological diseases, understanding that the technology has a high potential for its use as therapeutic tools. Taking into account that the rehabilitative process of motor disorders should extend beyond the inpatient condition, it’s necessary to involve low-cost technology, in order to have technological solutions that can approach the outpatient period at home. OBJECTIVE: to present the virtual applications-based RehabHand prototype for the rehabilitation of manipulative skills of the upper limbs in patients with neurological conditions and to determine the target population with respect to spinal cord injured patients. METHODS: Seven virtual reality applications have been designed and developed with a therapeutic sense, manipulated by means of Leap Motion Controller. The target population was determined from a sample of 40 people, healthy and patients, analyzing hand movements and gestures. RESULTS: The hand movements and gestures were estimated with a fitting rate between the range 0.607–0.953, determining the target population by cervical levels and upper extremity motor score. CONCLUSIONS: Leap Motion is suitable for a determined sample of cervical patients with a rehabilitation purpose.

Spinal cord injury (SCI) is characterized by the disruption of neuronal axons and the creation of an inhibitory environment for spinal tissue regeneration. For decades, researchers and clinicians have been devoting a great effort to develop novel therapeutic approaches which include the fabrication of biocompatible implants that could guide neural tissue repair in the lesion site in an attempt to recover the functionality of the nervous tissue. In this context, although fiberlike structures have been hypothesized to serve as a topographical guidance for axonal regrowth, work on the exploration of this type of materials is still limited for SCI. Aiming to develop such guidance platforms, we recently designed and explored in vitro reduced graphene oxide materials in the shape of microfibers (rGO-MFs). After preliminary studies to assess the feasibility of their implantation at the injured spinal cord in vivo, no evident signs of subacute local toxicity were noticed (10 days of implantation). In this work, we specifically examine for the first time the regenerative potential of these scaffolds, slightly modified in their fabrication for improved reproducibility, when chronically interfaced with a cervical spinal cord injury. After extensive characterization of their physicochemical properties and in vitro experiments with neural progenitor cells, their neural regenerative capacity in vivo is investigated in a rat experimental model of SCI after 4 months of implantation (chronic state). Behavioral tests involving the use of forelimbs are performed. Immunofluorescence studies evidence that rGO-MFs scaffolds foster the presence of neuronal structures along with blood vessels both within the epicenter and in the surroundings of the lesion area. Moreover, the inflammatory response does not worsen by the presence of this material. These findings outline the potential of rGO-MF-based scaffolds to promote regenerative features at the injured spinal cord such as axonal and vascular growth. Further studies including biological functionalization might improve their therapeutic potential by a synergistic effect of topographical and chemical cues, thus boosting neural repair after SCI.

Study designCohort study of patients with spinal cord injury (SCI)ObjectivesTo describe the clinical and analytical features of a Covid-19 infected cohort with SCI to contribute new knowledge for a more accurate diagnosis and to outline prevention measures.SettingThis study was conducted at the National Hospital for Paraplegics (Toledo, Spain).MethodsA cohort analysis of seven patients with SCI infected by Covid-19 was carried out. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical and radiographic findings were registered.ResultsRT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (5 out 7). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (6 out of 7). The second most common symptom was asthenia (4 out of 7), followed by dyspnea, cough and expectoration (3 out of 7 for each symptom). The MEWS score for Covid-19 severity rating was classified as severe in 5 out of 7. All but one patient showed radiological alterations evident in chest X-Rays at the time of diagnosis. All patients recovered gradually.ConclusionOur patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.

Neural tissue engineering approaches show increasing promise for the treatment of neural diseases including spinal cord injury, for which an efficient therapy is still missing. Encouraged by both positive findings on the interaction of carbon nanomaterials such as graphene with neural components and the necessity of more efficient guidance structures for neural repair, we herein study the potential of reduced graphene oxide (rGO) microfibers as substrates for neural growth in the injured central neural tissue. Compact, bendable, and conductive fibers are obtained. When coated with neural adhesive molecules (poly-L-lysine and N-cadherin), these microfibers behave as supportive substrates of highly interconnected cultures composed of neurons and glial cells for up to 21 days. Synaptic contacts close to rGO are identified. Interestingly, the colonization by meningeal fibroblasts is dramatically hindered by N-cadherin coating. Finally, in vivo studies reveal the feasible implantation of these rGO microfibers as a guidance platform in the injured rat spinal cord, without evident signs of subacute local toxicity. These positive findings boost further investigation at longer implantation times to prove the utility of these substrates as components of advanced therapies for enhancing repair in the damaged central neural tissue including the injured spinal cord., This work was supported by the Instituto de Salud Carlos III-MINECO-FEDER (CP13/00060), the Ministerio de Economía y Competitividad, and the Fondo Europeo de Desarrollo Regional (MAT2016-78857-R and MAT2015-68639-R, MINECO/FEDER, UE). It was also partially funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 737116.

The COVID-19 pandemic represents an unprecedented global challenge in this century. COVID-19 is a viral respiratory infection, yet the clinical characteristics of this infection differ in spinal cord injury patients from those observed in the general population. Cough and asthenia are the most frequent symptoms in this population. Moreover, infected spinal cord injury patients rarely present complications that require admission to an Intensive Care Unit, in contrast to the general population. Thus, there is a clear need to understand how COVID-19 affects spinal cord injury patients from a molecular perspective. Here, we employed an -omics strategy in order to identify variations in protein abundance in spinal cord injury patients with and without COVID-19. After a quantitative differential analysis using isobaric tags and mass spectrometry and a verification phase, we have found differences mainly related to coagulation and platelet activation. Our results suggest a key role of heparin in the response of spinal cord injury patients to COVID-19 infection, showing a significant correlation between these proteins and heparin dose. Although the number of patients is limited, these data may shed light on new therapeutic options to improve the management these patients and, possibly, those of the general population as well., This research was funded by the Consejo Superior de InvestigacionesCientíficas (CSIC) through the project PIE 202020E108, the Instituto de Salud Carlos III through the project PI18/00995 (co-funded by European Regional Development Fund/European Social Fund - “Investing in your future”) and Grant PRB3 (IPT17/0019—ISCIII-SGEFI/ERDF). The MCNU (PGC2018-097019-B-I00) and La Caixa (HR17-00247).

Incomplete cervical lesion is the most common type of human spinal cord injury (SCI) and causes permanent paresis of arm muscles, a phenomenon still incompletely understood in physiopathological and neuroanatomical terms. We performed spinal cord hemisection in adult rats at the caudal part of the segment C6, just rostral to the bulk of triceps brachii motoneurons, and analyzed the forces and kinematics of locomotion up to 4 months postlesion to determine the nature of motor function loss and recovery. A dramatic (50%), immediate and permanent loss of extensor force occurred in the forelimb but not in the hind limb of the injured side, accompanied by elbow and wrist kinematic impairments and early adaptations of whole-body movements that initially compensated the balance but changed continuously over the follow-up period to allow effective locomotion. Overuse of both contralateral legs and ipsilateral hind leg was evidenced since 5 days postlesion. Ipsilateral foreleg deficits resulted mainly from interruption of axons that innervate the spinal cord segments caudal to the lesion, because chronic loss (about 35%) of synapses was detected at C7 while only 14% of triceps braquii motoneurons died, as assessed by synaptophysin immunohistochemistry and retrograde neural tracing, respectively. We also found a large pool of propriospinal neurons projecting from C2-C5 to C7 in normal rats, with topographical features similar to the propriospinal premotoneuronal system of cats and primates. Thus, concurrent axotomy at C6 of brain descending axons and cervical propriospinal axons likely hampered spontaneous recovery of the focal neurological impairments.

The attractiveness of graphene-derived materials (GDMs) for neural applications has fueled their exploration as components of biomaterial interfaces contacting the brain and the spinal cord. In the last years, an increasing body of work has been published on the ability of these materials to create biocompatible and biofunctional substrates able to promote the growth and activity of neural cells in vitro and positively interact with neural tissues when implanted in vivo. Encouraging results in the central nervous tissue might impulse the study of GDMs towards preclinical arena. In this mini-review article, we revise the most relevant literature on the interaction of GDMs with the spinal cord. Studies involving the implantation of these materials in vivo in the injured spinal cord are first discussed, followed by models with spinal cord slides ex vivo and a final description of selected results with neural cells in vitro. A closing debate of the major conclusions of these results is presented to boost the investigation of GDMs in the field., This project has received funding from the Agencia Estatal de Investigación of Spain and the Fondo Europeo de Desarrollo Regional (MAT2016-78857-R, AEI/FEDER, UE).

Incomplete cervical lesion is the most common type of human spinal cord injury (SCI) and causes permanent paresis of arm muscles, a phenomenon still incompletely understood in physiopathological and neuroanatomical terms. We performed spinal cord hemisections in adult rats at the caudal part of the segment C6, and analysed the forces and kinematics of locomotion up to four months post-injury to determine the nature of motor function loss and recovery. A severe (50 %), immediate and permanent loss of extensor force occurred in the forelimb but not in the hindlimb of the injured side, accompanied by elbow and wrist kinematic impairments and early adaptations of whole-body movements that initially compensated the balance but changed continuously over the follow-up period to allow effective locomotion.

The rat is widely used for modeling human spinal cord injury (SCI) and paraplegia. However, quadruped animals adapt trunk, forelimb and hindlimb movements to compensate for deficits, improving their behavioral scores and complicating the interpretation of spontaneous and treatment-induced function recovery. The kinematics of locomotion was studied in rats, both normal and after SCI (T9 contusion), and variables indicative of hindlimb function were related to brain-spinal cord connections (BSCC) spared during lesioning. Normal animals showed forward velocities characteristic of fast walking. The hind paw was placed approximately three centimeters in front of the hip at the initial contact. Hip height decreased during the first third of hindlimb stance and increased later. Mild and moderate spinal cord contusions destroyed the gray matter and adjacent axons but spared the ventrolateral tracts to various degrees. Injured animals placed the hindpaw in a more caudal position than normal and showed reduced forward velocity and hip height. Knee extension was also impaired, and both hindlimb and forelimb steps were adapted to compensate for the deficits. BSCC was estimated by averaging the transverse area of white matter at the lesion epicenter and the percentage of brain neurons labeled after peroxidase injection into L2 and L3. Recovery of hindlimb motor function was proportional to the amount of BSCC. On average, injured animals retained 18% of BSSC and recovered 23% of hindlimb function. These findings show that kinematic analysis is a reliable tool for assessing locomotor deficits and compensations and suggest limited spontaneous motor plasticity after SCI.