36 results on '"López-Dolado E"'
Search Results
2. High-Performance Implantable Sensors based on Anisotropic Magnetoresistive La0.67Sr0.33MnO3 for Biomedical Applications
- Author
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Vera A., Martínez I., Enger L.G., Guillet B., Guerrero R., Diez J.M., Rousseau O., Lam Chok Sing M., Pierron V., Perna, Paolo, Hernández J.J., Rodríguez, Isabel, Calaresu I., Meier A., Huck C., Domínguez-Bajo A., González-Mayorga A., López-Dolado E., Serrano M.C., Ballerini L., Pérez, Lucas, Miranda, Rodolfo, Flament S., González, Teresa, Méchin L., Camarero, Julio, Vera A., Martínez I., Enger L.G., Guillet B., Guerrero R., Diez J.M., Rousseau O., Lam Chok Sing M., Pierron V., Perna, Paolo, Hernández J.J., Rodríguez, Isabel, Calaresu I., Meier A., Huck C., Domínguez-Bajo A., González-Mayorga A., López-Dolado E., Serrano M.C., Ballerini L., Pérez, Lucas, Miranda, Rodolfo, Flament S., González, Teresa, Méchin L., and Camarero, Julio
- Published
- 2022
3. Nanostructured gold electrodes promote neural maturation and network connectivity
- Author
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Domínguez-Bajo A., Rosa J.M., González-Mayorga A., Rodilla B.L., Arché-Núñez A., Benayas E., Ocón P., Pérez, Lucas, Camarero, Julio, Miranda, Rodolfo, González, Teresa, Aguilar J., López-Dolado E., Serrano M.C., Domínguez-Bajo A., Rosa J.M., González-Mayorga A., Rodilla B.L., Arché-Núñez A., Benayas E., Ocón P., Pérez, Lucas, Camarero, Julio, Miranda, Rodolfo, González, Teresa, Aguilar J., López-Dolado E., and Serrano M.C.
- Published
- 2021
4. Interfacing Neurons with Nanostructured Electrodes Modulates Synaptic Circuit Features
- Author
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Domínguez-Bajo A., Rodilla B.L., Calaresu I., Arché-Núñez A., González-Mayorga A., Scaini D., Pérez L., Camarero J., Miranda R., López-Dolado E., González M.T., Ballerini L., Serrano M.C. and A.D.?B. and B.L.R. contributed equally to this work. This work was funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 737116 (ByAxon). The work was also partially funded by the Spanish Ministry of Science and Innovation through project BiSURE (Grant: DPI2017?90058?R) and the ‘Severo Ochoa’ Programme for Centers of Excellence in R&D (MINECO, Grant SEV?2016?0686), as well as by the Comunidad de Madrid project NanoMagCOST (CM S2018/NMT?4321). BLR acknowledges UCM for her predoctoral fellowship. Authors are thankful to Dr. Esperanza Salvador, Isidoro Poveda, Gabriel Carro, Enrique Rodríguez, Dr. Francisco Urbano, and Dr. Covadonga Agudo from the Servicio Interdepartamental de Investigación at the Universidad Autónoma de Madrid for respective assistance with SEM, FESEM, and TEM studies. Sylvia Gutiérrez from the Advanced Light Microscopy Service at the Centro Nacional de Biotecnología (CNB?CSIC) is acknowledged for her assistance with CLSM studies.
- Published
- 2020
5. Interfacing Neurons with Nanostructured Electrodes Modulates Synaptic Circuit Features
- Author
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Domínguez-Bajo A., Rodilla B.L., Calaresu I., Arché-Núñez A., González-Mayorga A., Scaini D., Pérez, Lucas, Camarero, Julio, Miranda, Rodolfo, López-Dolado E., González, Teresa, Ballerini L., Serrano M.C., Domínguez-Bajo A., Rodilla B.L., Calaresu I., Arché-Núñez A., González-Mayorga A., Scaini D., Pérez, Lucas, Camarero, Julio, Miranda, Rodolfo, López-Dolado E., González, Teresa, Ballerini L., and Serrano M.C.
- Published
- 2020
6. Cortical correlates of TMS-induced phantom hand movements revealed with concurrent TMS-fMRI
- Author
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Bestmann, S., Oliviero, A., Voss, M., Dechent, P., Lopez-Dolado, E., Driver, J., and Baudewig, J.
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- 2006
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7. Concurrent Validity of a Virtual Version of Box and Block Test for Patients with Neurological Disorders
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Alvarez-Rodríguez, M., primary, López-Dolado, E., additional, Salas-Monedero, M., additional, Lozano-Berrio, V., additional, Ceruelo-Abajo, S., additional, Gil-Agudo, A., additional, and de los Reyes-Guzmán, A., additional
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- 2020
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8. In Vivo Rat Spinal Cord and Striated Muscle Monitoring Using the Current Interruption Method and Bioimpedance Measurements
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Hernández-Balaguera, E., primary, López-Dolado, E., additional, and Polo, J. L., additional
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- 2018
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9. Daño medular intraoperatorio en cirugía de escoliosis idiopática: reinstrumentar y cuándo
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Talavera-Mosquera, J.M., primary and López-Dolado, E., additional
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- 2016
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10. Obtaining electrical equivalent circuits of biological tissues using the current interruption method, circuit theory and fractional calculus
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Hernández-Balaguera, E., primary, López-Dolado, E., additional, and Polo, J. L., additional
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- 2016
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11. Intervenciones que mejoran el pronóstico en la neurofibromatosis tipo 2: a propósito de un caso
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Rodríguez Palero, S., primary, Muñoz González, L., additional, Amosa Delgado, M., additional, Iodrovo, F., additional, and López Dolado, E., additional
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- 2011
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12. Tratamiento de la tendinopatía calcificante de hombro: ¿iontoforesis con ácido acético u onda corta?
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Jiménez-García, D., primary, López-Dolado, E., additional, and López-Zarzuela, M.C., additional
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- 2008
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13. Tratamiento intervencionista del dolor neuropático
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López-Dolado, E., primary and Calderón Muñoz, F., additional
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- 2006
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14. 3d graphene oxide scaffolds as pro-regenerative biomaterials in the rat injured spinal cord
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Domínguez-Bajo, A., F. Ankor González-Mayorga, López-Dolado, E., and Serrano, M. C.
15. [Gait training in incomplete spinal cord injuries with body weight support]
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Alcobendas-Maestro M, López-Dolado E, Ana Esclarín-Ruz, and Mc, Valdizán-Valledor
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Adult ,Male ,Spinal Cord ,Body Weight ,Humans ,Female ,Walking ,Middle Aged ,Gait ,Physical Therapy Modalities ,Spinal Cord Injuries ,Exercise Therapy - Abstract
A spinal cord injury implies the loss of or alteration to the gait pattern. Stimulating the pattern generating centres in the sublesional spinal cord determines the appearance of flexion and extension automatisms that are useful for gait training in patients with spinal cord injuries. These centres can be stimulated using a treadmill and supporting the body weight by means of a harness.To be able to trigger spinal cord automatisms and to stimulate pattern generating centres. To determine the value of an electromechanical system for mobilising the lower limbs as a complement to the treadmill and body weight support. To study changes in muscle tone.A short gait training programming was carried out with ten individuals with incomplete spinal cord injuries who satisfied eligibility-exclusion criteria using a treadmill in association with a body weight support system and an electromechanical system for mobilising the lower limbs.Spinal cord flexion and extension automatisms were stimulated and an important improvement in spasticity was achieved. Longer programmes are needed in order to evidence changes in the gait pattern and in muscular balance.
16. Flexible metallic core-shell nanostructured electrodes for neural interfacing.
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Rodilla BL, Arché-Núñez A, Ruiz-Gómez S, Domínguez-Bajo A, Fernández-González C, Guillén-Colomer C, González-Mayorga A, Rodríguez-Díez N, Camarero J, Miranda R, López-Dolado E, Ocón P, Serrano MC, Pérez L, and González MT
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- Rats, Animals, Electrodes, Microelectrodes, Neurons physiology, Electric Impedance, Nanostructures, Nanowires
- Abstract
Electrodes with nanostructured surface have emerged as promising low-impedance neural interfaces that can avoid the charge-injection restrictions typically associated to microelectrodes. In this work, we propose a novel approximation, based on a two-step template assisted electrodeposition technique, to obtain flexible nanostructured electrodes coated with core-shell Ni-Au vertical nanowires. These nanowires benefit from biocompatibility of the Au shell exposed to the environment and the mechanical properties of Ni that allow for nanowires longer and more homogeneous in length than their only-Au counterparts. The nanostructured electrodes show impedance values, measured by electrochemical impedance spectroscopy (EIS), at least 9 times lower than those of flat reference electrodes. This ratio is in good accordance with the increased effective surface area determined both from SEM images and cyclic voltammetry measurements, evidencing that only Au is exposed to the medium. The observed EIS profile evolution of Ni-Au electrodes over 7 days were very close to those of Au electrodes and differently from Ni ones. Finally, the morphology, viability and neuronal differentiation of rat embryonic cortical cells cultured on Ni-Au NW electrodes were found to be similar to those on control (glass) substrates and Au NW electrodes, accompanied by a lower glial cell differentiation. This positive in-vitro neural cell behavior encourages further investigation to explore the tissue responses that the implantation of these nanostructured electrodes might elicit in healthy (damaged) neural tissues in vivo, with special emphasis on eventual tissue encapsulation., (© 2024. The Author(s).)
- Published
- 2024
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17. Research Priorities of the Pediatric Spinal Cord Injury Population: An International Insight for Rehabilitation Care.
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Ríos-León M, Onal B, Arango-Lasprilla JC, Augutis M, Graham A, Kelly EH, Kontaxakis A, López-Dolado E, Scheel-Sailer A, Valiullina S, and Taylor J
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- Adult, Adolescent, Humans, Child, Cross-Sectional Studies, Caregivers, Walking, Research, Spinal Cord Injuries epidemiology, Spinal Cord Injuries rehabilitation
- Abstract
Background: Although feedback from people with adult-onset spinal cord injury (SCI) has been considered for new rehabilitation programs, little is known about the priorities of the pediatric-onset SCI population. This study describes and compares health and life (H&L) domain research priorities of youth with pediatric-onset SCI and their parents/caregivers., Methods: A cross-sectional survey, designed by the Pan-European Paediatric Spinal Cord Injury (PEPSCI) Collaboration, was performed at six European countries. Dyad data from 202 participants, youth with pediatric-onset SCI (n = 101) and their parents/caregivers (n = 101), were analyzed with the PEPSCI H&L domain surveys., Results: The cohort was composed of 8 to 12-year-olds (30.7%), 13 to 17-year-olds (38.6%), and 18 to 25-year-olds (30.7%). The top three H&L domain research priorities reported by parents/caregivers of 8 to 12-year-olds were "walking/ability to move" (91%), "bladder" function (90%), and "general health/feel" (89%), compared with "physical function" (93%), "general health/feel" (90%), and "walking/ability to move" (89%) rated by parents/caregivers of 13 to 25-year-olds. "Bowel" function (85%), "leg/foot movement" (84%), and "bladder" function (84%) were reported as priorities by 13 to 25-year-olds, whereas "physical function" (84%), "experience at school" (83%), and "general mood" were highlighted by 8 to 12-year-olds. The top 10 priorities preferred by 13 to 25-year-olds when compared with the top 10 priorities reported by their parents/caregivers, included problems related to "bowel" and "pain.", Conclusions: Health domain research priorities were highlighted by 13 to 25-year-olds, compared with their parents/caregivers who equally identified H&L domains. This survey will aid health care and clinical research organizations to engage stakeholders to implement a comprehensive research strategy for the pediatric SCI population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2024
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18. Pediatric health and life domain priorities: A national survey of people with spinal cord injury and their parents and caregivers.
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Ríos-León M, Onal B, Arango-Lasprilla JC, Augutis M, Civicos-Sanchez N, Graham A, Kelly EH, López-Dolado E, Scheel-Sailer A, Subiñas-Medina P, and Taylor J
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- Adolescent, Humans, Child, Young Adult, Adult, Caregivers, Cross-Sectional Studies, Paraplegia rehabilitation, Activities of Daily Living, Spinal Cord Injuries rehabilitation
- Abstract
Context/objective: No information is available regarding priorities for pediatric-onset spinal cord injury (SCI). This study described the Health and Life (H&L) domain priorities of youth with pediatric-onset SCI and their parents/caregivers living in Spain., Design: A cross-sectional survey., Setting: Two SCI rehabilitation centers., Participants: Sixty participants, youth with pediatric-onset SCI (n = 26) and parents/caregivers (n = 34)., Interventions: Not applicable., Outcome Measures: Median overall priorities calculated on the basis of importance, unhappiness, and research measured with a new survey of pediatric H&L domains and rated using a 5-point Likert Scale., Results: A total of 60 surveys were received providing information on 35 individuals with SCI: 2-7-year-olds (25.7%), 8-12-year-olds (22.9%), 13-17-year-olds (31.4%), and 18-25-year-olds (20.0%). The top three overall H&L priorities reported by parents/caregivers of 2-12-year-olds were "parenthood expectations" (84%), "leg/foot movement" (83%), and "bladder" function (83%), compared to "dressing/undressing" (78%), "walking/ability to move" (77%) and "bladder" function (77%) rated for 13-25-year-olds. "Sit-to-stand" (79%), "leg/foot movement" (78%) and "arm/hand movement" (77%) were reported as priorities by 13-25-year-olds. The 13-25-year-olds highlighted "sit-to-stand" (100%), "eating/drinking" (54%), and "physical function" (94%) as their top unhappiness, importance, and research priorities, respectively. Significant differences between tetraplegia and paraplegia were found in "mobility in the community" (unhappiness item) for 13-25-years-old., Conclusion: Health domains were considered the top overall H&L priorities by parents/caregivers of 13-25-year-olds, compared to life domains reported for their 2-12-year-olds. This survey will aid rehabilitation professionals to engage stakeholders to implement a comprehensive SCI management program for the pediatric population.
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- 2024
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19. High-Performance Implantable Sensors based on Anisotropic Magnetoresistive La 0.67 Sr 0.33 MnO 3 for Biomedical Applications.
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Vera A, Martínez I, Enger LG, Guillet B, Guerrero R, Diez JM, Rousseau O, Lam Chok Sing M, Pierron V, Perna P, Hernández JJ, Rodríguez I, Calaresu I, Meier A, Huck C, Domínguez-Bajo A, González-Mayorga A, López-Dolado E, Serrano MC, Ballerini L, Pérez L, Miranda R, Flament S, González MT, Méchin L, and Camarero J
- Subjects
- Anisotropy, Polymers, Prostheses and Implants, Magnetic Fields
- Abstract
We present the design, fabrication, and characterization of an implantable neural interface based on anisotropic magnetoresistive (AMR) magnetic-field sensors that combine reduced size and high performance at body temperature. The sensors are based on La
0.67 Sr0.33 MnO3 (LSMO) as a ferromagnetic material, whose epitaxial growth has been suitably engineered to get uniaxial anisotropy and large AMR output together with low noise even at low frequencies. The performance of LSMO sensors of different film thickness and at different temperatures close to 37 °C has to be explored to find an optimum sensitivity of ∼400%/T (with typical detectivity values of 2 nT·Hz-1/2 at a frequency of 1 Hz and 0.3 nT·Hz-1/2 at 1 kHz), fitted for the detection of low magnetic signals coming from neural activity. Biocompatibility tests of devices consisting of submillimeter-size LSMO sensors coated by a thin poly(dimethyl siloxane) polymeric layer, both in vitro and in vivo , support their high suitability as implantable detectors of low-frequency biological magnetic signals emerging from heterogeneous electrically active tissues.- Published
- 2023
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20. Nanostructured gold electrodes promote neural maturation and network connectivity.
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Domínguez-Bajo A, Rosa JM, González-Mayorga A, Rodilla BL, Arché-Núñez A, Benayas E, Ocón P, Pérez L, Camarero J, Miranda R, González MT, Aguilar J, López-Dolado E, and Serrano MC
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- Animals, Electrodes, Gold, Nanotechnology, Rats, Nanostructures, Nanowires
- Abstract
Progress in the clinical application of recording and stimulation devices for neural diseases is still limited, mainly because of suboptimal material engineering and unfavorable interactions with biological entities. Nanotechnology is providing upgraded designs of materials to better mimic the native extracellular environment and attain more intimate contacts with individual neurons, besides allowing for the miniaturization of the electrodes. However, little progress has been done to date on the understanding of the biological impact that such neural interfaces have on neural network maturation and functionality. In this work, we elucidate the effect of a gold (Au) highly ordered nanostructure on the morphological and functional interactions with neural cells and tissues. Alumina-templated Au nanostructured electrodes composed of parallel nanowires of 160 nm in diameter and 1.2 μm in length (Au-NWs), with 320 nm of pitch, are designed and characterized. Equivalent non-structured Au electrodes (Au-Flat) are used for comparison. By using diverse techniques in in vitro cell cultures including live calcium imaging, we found that Au-NWs interfaced with primary neural cortical cells for up to 14 days allow neural networks growth and increase spontaneous activity and ability of neuronal synchronization, thus indicating that nanostructured features favor neuronal network. The enhancement in the number of glial cells found is hypothesized to be behind these beneficial functional effects. The in vivo effect of the implantation of these nanostructured electrodes and its potential relevance for future clinical applicability has been explored in an experimental model of rat spinal cord injury. Subacute responses to implanted Au-NWs show no overt reactive or toxic biological reactions besides those triggered by the injury itself. These results highlight the translational potential of Au-NWs electrodes for in vivo applications as neural interfaces in contact with central nervous tissues including the injured spinal cord., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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21. RehabHand: Oriented-tasks serious games for upper limb rehabilitation by using Leap Motion Controller and target population in spinal cord injury.
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de Los Reyes-Guzmán A, Lozano-Berrio V, Alvarez-Rodríguez M, López-Dolado E, Ceruelo-Abajo S, Talavera-Díaz F, and Gil-Agudo A
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- Adult, Female, Humans, Male, Middle Aged, Motion, Upper Extremity physiopathology, Neurological Rehabilitation methods, Spinal Cord Injuries rehabilitation, Video Games, Virtual Reality
- Abstract
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.
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- 2021
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22. Interfacing Neurons with Nanostructured Electrodes Modulates Synaptic Circuit Features.
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Domínguez-Bajo A, Rodilla BL, Calaresu I, Arché-Núñez A, González-Mayorga A, Scaini D, Pérez L, Camarero J, Miranda R, López-Dolado E, González MT, Ballerini L, and Serrano MC
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- Animals, Calcium Signaling, Cells, Cultured, Cerebral Cortex cytology, Equipment Design, Female, Hippocampus cytology, Microelectrodes, Rats, Rats, Wistar, Electric Stimulation instrumentation, Nanotechnology instrumentation, Nanowires chemistry, Neurons cytology, Neurons physiology, Synapses physiology
- Abstract
Understanding neural physiopathology requires advances in nanotechnology-based interfaces, engineered to monitor the functional state of mammalian nervous cells. Such interfaces typically contain nanometer-size features for stimulation and recording as in cell-non-invasive extracellular microelectrode arrays. In such devices, it turns crucial to understand specific interactions of neural cells with physicochemical features of electrodes, which could be designed to optimize performance. Herein, versatile flexible nanostructured electrodes covered by arrays of metallic nanowires are fabricated and used to investigate the role of chemical composition and nanotopography on rat brain cells in vitro. By using Au and Ni as exemplary materials, nanostructure and chemical composition are demonstrated to play major roles in the interaction of neural cells with electrodes. Nanostructured devices are interfaced to rat embryonic cortical cells and postnatal hippocampal neurons forming synaptic circuits. It is shown that Au-based electrodes behave similarly to controls. Contrarily, Ni-based nanostructured electrodes increase cell survival, boost neuronal differentiation, and reduce glial cells with respect to flat counterparts. Nonetheless, Au-based electrodes perform superiorly compared to Ni-based ones. Under electrical stimulation, Au-based nanostructured substrates evoke intracellular calcium dynamics compatible with neural networks activation. These studies highlight the opportunity for these electrodes to excite a silent neural network by direct neuronal membranes depolarization., (© 2020 The Authors. Published by Wiley-VCH GmbH.)
- Published
- 2020
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23. Clinical features of coronavirus disease 2019 (COVID-19) in a cohort of patients with disability due to spinal cord injury.
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Rodríguez-Cola M, Jiménez-Velasco I, Gutiérrez-Henares F, López-Dolado E, Gambarrutta-Malfatti C, Vargas-Baquero E, and Gil-Agudo Á
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- Adult, Aged, COVID-19, Cohort Studies, Coronavirus Infections complications, Disabled Persons, Female, Humans, Male, Middle Aged, Pandemics, Pneumonia, Viral complications, Risk Factors, SARS-CoV-2, Spain, Betacoronavirus, Coronavirus Infections diagnosis, Pneumonia, Viral diagnosis, Spinal Cord Injuries complications
- Abstract
Study Design: Cohort study of patients with spinal cord injury (SCI)., Objectives: To describe the clinical and analytical features of a coronavirus disease 2019 (Covid-19) infected cohort with SCI to enable accurate diagnosis and to outline prevention measures., Setting: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain)., Methods: A cohort analysis of seven patients with SCI infected by Covid-19 was performed. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical, and radiographic findings were registered., Results: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (five out of seven). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (six out of seven). The second most common symptom was asthenia (four out of seven), followed by dyspnea, cough, and expectoration (three out of seven for each symptom). The Modified Early Warning System score for Covid-19 severity rating was classified as severe in five out of seven cases. All but one patient showed radiological alterations evident in chest X-rays at the time of diagnosis. All patients recovered gradually., Conclusion: Our 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.
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- 2020
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24. Lessons learned from the coronavirus disease 2019 (Covid-19) outbreak in a monographic center for spinal cord injury.
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López-Dolado E and Gil-Agudo A
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- COVID-19, Coronavirus Infections epidemiology, Coronavirus Infections prevention & control, Coronavirus Infections transmission, Humans, Pandemics prevention & control, Pneumonia, Viral epidemiology, Pneumonia, Viral prevention & control, Pneumonia, Viral transmission, Risk Factors, SARS-CoV-2, Betacoronavirus, Coronavirus Infections complications, Disease Outbreaks, Pneumonia, Viral complications, Spinal Cord Injuries complications
- Published
- 2020
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25. Graphene Oxide Microfibers Promote Regenerative Responses after Chronic Implantation in the Cervical Injured Spinal Cord.
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Domínguez-Bajo A, González-Mayorga A, López-Dolado E, Munuera C, García-Hernández M, and Serrano MC
- Subjects
- Animals, Rats, Reproducibility of Results, Spinal Cord, Cervical Cord, Graphite
- Abstract
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.
- Published
- 2020
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26. Myelinated axons and functional blood vessels populate mechanically compliant rGO foams in chronic cervical hemisected rats.
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Domínguez-Bajo A, González-Mayorga A, Guerrero CR, Palomares FJ, García R, López-Dolado E, and Serrano MC
- Subjects
- Animals, Axons pathology, Biocompatible Materials chemistry, Graphite chemistry, Male, Neovascularization, Physiologic, Rats, Rats, Wistar, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology, Tissue Scaffolds chemistry, Biocompatible Materials therapeutic use, Graphite therapeutic use, Nerve Regeneration, Spinal Cord Injuries therapy
- Abstract
Neural diseases at the central nervous system including spinal cord injury (SCI) remain therapeutic challenges. Graphene materials are being delineated as alternative tools for neural repair. Herein, the regenerative ability of reduced graphene oxide (rGO) scaffolds to support pivotal features of neural repair at 4 months after SCI is assessed by an interdisciplinary approach. 3D randomly porous foams have been prepared in mechanical compliance with neural cells and tissues (Young's modulus of 1.3 ± 1.0 kPa) as demonstrated by atomic force microscopy techniques applied ex vivo. After implantation, the significant increase in Young's modulus caused by massive cell/protein infiltration does not alter the mechanical performance of the contralateral spinal cord but provides mechanical stability to the lesion. These aerogels appear fully vascularized and populated with neurites, some of them being myelinated excitatory axons. Clinically-inspired magnetic resonance imaging studies demonstrate that the scaffolds significantly reduce perilesional damage with respect to rats without implants and cause no compressive damage in the contralateral hemicord and rostral/caudal regions. The rGO implants do not either alter the rat spontaneous behaviour or induce toxicity in major organs. Finally, preliminary data suggest hints of rGO sheets dissociation and eventual degradation at the injured spinal cord for the first time. In summary, these 3D porous rGO scaffolds are able to induce, without any further biological functionalization, a compilation of positive effects that have been rarely described before, if ever, for any other material implanted in the injured spinal cord., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
- Published
- 2019
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27. Favorable Biological Responses of Neural Cells and Tissue Interacting with Graphene Oxide Microfibers.
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González-Mayorga A, López-Dolado E, Gutiérrez MC, Collazos-Castro JE, Ferrer ML, Del Monte F, and Serrano MC
- Abstract
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., Competing Interests: The authors declare no competing financial interest.
- Published
- 2017
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28. Graphene-Derived Materials Interfacing the Spinal Cord: Outstanding in Vitro and in Vivo Findings.
- Author
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Domínguez-Bajo A, González-Mayorga A, López-Dolado E, and Serrano MC
- Abstract
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.
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- 2017
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29. Immunomodulatory and angiogenic responses induced by graphene oxide scaffolds in chronic spinal hemisected rats.
- Author
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López-Dolado E, González-Mayorga A, Gutiérrez MC, and Serrano MC
- Subjects
- Angiogenesis Inducing Agents chemistry, Animals, Axons metabolism, Axons pathology, Biocompatible Materials chemistry, Biocompatible Materials therapeutic use, Graphite chemistry, Humans, Immunomodulation, Male, Microscopy, Confocal, Microscopy, Electron, Transmission, Oxides chemistry, Rats, Wistar, Regeneration, Spinal Cord blood supply, Spinal Cord pathology, Spinal Cord Injuries immunology, Spinal Cord Injuries pathology, Spinal Cord Injuries surgery, Spinal Cord Regeneration, Angiogenesis Inducing Agents therapeutic use, Graphite therapeutic use, Neurons pathology, Oxides therapeutic use, Spinal Cord Injuries therapy, Tissue Scaffolds chemistry
- Abstract
Attractive physic-chemical features of graphene oxide (GO) and promising results in vitro with neural cells encourage its exploration for biomedical applications including neural regeneration. Fueled by previous findings at the subacute state, we herein investigate for the first time chronic tissue responses (at 30 days) to 3D scaffolds composed of partially reduced GO (rGO) when implanted in the injured rat spinal cord. These studies aim to define fibrotic, inflammatory and angiogenic changes at the lesion site induced by the chronic implantation of these porous structures. Injured animals receiving no scaffolds show badly structured lesion zones and more cavities than those carrying rGO materials, thus pointing out a significant role of the scaffolds in injury stabilization and sealing. Notably, GFAP(+) cells and pro-regenerative macrophages are evident at their interface. Moreover, rGO scaffolds support angiogenesis around and, more importantly, inside their structure, with abundant and functional new blood vessels in whose proximities inside the scaffolds some regenerated neuronal axons are found. On the contrary, lesion areas without rGO scaffolds show a diminished quantity of blood vessels and no axons at all. These findings provide a foundation for the usefulness of graphene-based materials in the design of novel biomaterials for spinal cord repair and encourage further investigation for the understanding of neural tissue responses to this kind of materials in vivo., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
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- 2016
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30. Subacute Tissue Response to 3D Graphene Oxide Scaffolds Implanted in the Injured Rat Spinal Cord.
- Author
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López-Dolado E, González-Mayorga A, Portolés MT, Feito MJ, Ferrer ML, Del Monte F, Gutiérrez MC, and Serrano MC
- Subjects
- Animals, Central Nervous System metabolism, Male, Nerve Regeneration, Neurons cytology, Neurons metabolism, Oxides chemistry, Rats, Rats, Wistar, Graphite chemistry, Prostheses and Implants, Spinal Cord metabolism, Tissue Scaffolds chemistry
- Abstract
The increasing prevalence and high sanitary costs of lesions affecting the central nervous system (CNS) at the spinal cord are encouraging experts in different fields to explore new avenues for neural repair. In this context, graphene and its derivatives are attracting significant attention, although their toxicity and performance in the CNS in vivo remains unclear. Here, the subacute tissue response to 3D flexible and porous scaffolds composed of partially reduced graphene oxide is investigated when implanted in the injured rat spinal cord. The interest of these structures as potentially useful platforms for CNS regeneration mainly relies on their mechanical compliance with neural tissues, adequate biocompatibility with neural cells in vitro and versatility to carry topographical and biological guidance cues. Early tissue responses are thoroughly investigated locally (spinal cord at C6 level) and in the major organs (i.e., kidney, liver, lung, and spleen). The absence of local and systemic toxic responses, along with the positive signs found at the lesion site (e.g., filler effect, soft interface for no additional scaring, preservation of cell populations at the perilesional area, presence of M2 macrophages), encourages further investigation of these materials as promising components of more efficient material-based platforms for CNS repair., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2015
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31. Dynamic motor compensations with permanent, focal loss of forelimb force after cervical spinal cord injury.
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López-Dolado E, Lucas-Osma AM, and Collazos-Castro JE
- Subjects
- Animals, Biomechanical Phenomena, Cervical Vertebrae, Forelimb innervation, Forelimb physiopathology, Hindlimb innervation, Hindlimb physiopathology, Immunohistochemistry, Male, Rats, Rats, Wistar, Spinal Cord Injuries complications, Motor Activity physiology, Nerve Regeneration physiology, Recovery of Function physiology, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology
- Abstract
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.
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- 2013
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32. Spinal cord direct current stimulation: finite element analysis of the electric field and current density.
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Hernández-Labrado GR, Polo JL, López-Dolado E, and Collazos-Castro JE
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- Animals, Cervical Vertebrae, Electrodes, Electromagnetic Fields, Finite Element Analysis, Humans, Spinal Cord Injuries physiopathology, Spinal Cord Injuries therapy, Electric Stimulation Therapy methods, Models, Neurological, Spinal Cord physiology
- Abstract
Applied low-intensity direct current (DC) stimulates and directs axonal growth in models of spinal cord injury (SCI) and may have therapeutic value in humans. Using higher electric strengths will probably increase the beneficial effects, but this faces the risk of tissue damage by electricity or toxic reactions at the electrode-tissue interface. To inform the optimisation of DC-based therapeutics, we developed a finite element model (FEM) of the human cervical spine and calculated the electric fields (EFs) and current densities produced by electrodes of different size, geometry and location. The presence of SCI was also considered. Three disc electrodes placed outside the spine produced low-intensity, uneven EFs, whereas the EFs generated by the same electrodes located epidurally were about three times more intense. Changes in electrical conductivity after SCI had little effect on the EF magnitudes. Uniformly distributed EFs were obtained with five disc electrodes placed around the dura mater, but not with a paddle-type electrode placed in the dorsal epidural space. Replacing the five disc electrodes by a single, large band electrode yielded EFs > 5 mV/mm with relatively low current density (2.5 μA/mm(2)) applied. With further optimisation, epidural, single-band electrodes might enhance the effectiveness of spinal cord DC stimulation.
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- 2011
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33. [Acute transverse myelitis: a clinical review and algorithm for diagnostic intervention].
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Gómez-Argüelles JM, Sánchez-Solla A, López-Dolado E, Díez-De la Lastra E, and Florensa J
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- Diagnosis, Differential, Humans, Algorithms, Myelitis, Transverse diagnosis
- Abstract
Introduction: Under the term of acute transverse myelitis (ATM), there are included a heterogeneous group of diseases, with the nexus common to produce an inflammatory focal injury of the spinal cord, of acute form. In order to try to group all the etiologies that can provoke this affectation, it is nowadays tried to define several groups of pathologies with a common nexus: those ATM associated to some process, or at least predisposed of the ATM, like are certain infections, immunological systemic and/or multifocal processes, and inclusive tumors, but when we did not get to know this triggering factor, then calling them idiopathic ATM., Aim: To know the different classes from existing ATM, creating an algorithm diagnosis that helps to this classification of ordinate form, simplifying the work to the clinicians that faces a ATM, exposing its differential diagnosis, prognosis and possible treatment., Development: For it we consulted the last guides and works published related to the ATM, mainly from the diagnostic and therapeutic point of view., Conclusions: Our knowledge of the ATM is being constantly modified with the coming of new diagnostic techniques and theories that try to explain their origin, probably immunological. Unfortunately, the treatment, and therefore the prognosis, has not varied in the same proportion to the knowledge that we are acquiring in the other areas. Without a doubt, it is a way important to walk, but the next future can teach to us more on this disease.
- Published
- 2009
34. Locomotor deficits and adaptive mechanisms after thoracic spinal cord contusion in the adult rat.
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Collazos-Castro JE, López-Dolado E, and Nieto-Sampedro M
- Subjects
- Animals, Axonal Transport, Biomechanical Phenomena, Denervation, Disability Evaluation, Disease Models, Animal, Efferent Pathways injuries, Efferent Pathways pathology, Efferent Pathways physiopathology, Forelimb innervation, Forelimb physiopathology, Gait Disorders, Neurologic diagnosis, Hindlimb innervation, Hindlimb physiopathology, Horseradish Peroxidase, Male, Muscle Contraction physiology, Muscle, Skeletal innervation, Muscle, Skeletal physiopathology, Neurons cytology, Neurons physiology, Rats, Rats, Wistar, Spinal Cord pathology, Spinal Cord physiopathology, Spinal Cord Injuries diagnosis, Thoracic Vertebrae, Adaptation, Physiological physiology, Gait Disorders, Neurologic physiopathology, Neuronal Plasticity physiology, Recovery of Function physiology, Spinal Cord Injuries physiopathology
- Abstract
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.
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- 2006
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35. [Gait training in incomplete spinal cord injuries with body weight support].
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Alcobendas-Maestro M, López-Dolado E, Esclarín de Ruz A, and Valdizán-Valledor MC
- Subjects
- Adult, Body Weight, Female, Humans, Male, Middle Aged, Spinal Cord pathology, Spinal Cord physiology, Spinal Cord Injuries pathology, Spinal Cord Injuries physiopathology, Walking, Exercise Therapy, Gait, Physical Therapy Modalities, Spinal Cord Injuries rehabilitation
- Abstract
Introduction: A spinal cord injury implies the loss of or alteration to the gait pattern. Stimulating the pattern generating centres in the sublesional spinal cord determines the appearance of flexion and extension automatisms that are useful for gait training in patients with spinal cord injuries. These centres can be stimulated using a treadmill and supporting the body weight by means of a harness., Aims: To be able to trigger spinal cord automatisms and to stimulate pattern generating centres. To determine the value of an electromechanical system for mobilising the lower limbs as a complement to the treadmill and body weight support. To study changes in muscle tone., Patients and Methods: A short gait training programming was carried out with ten individuals with incomplete spinal cord injuries who satisfied eligibility-exclusion criteria using a treadmill in association with a body weight support system and an electromechanical system for mobilising the lower limbs., Results and Conclusions: Spinal cord flexion and extension automatisms were stimulated and an important improvement in spasticity was achieved. Longer programmes are needed in order to evidence changes in the gait pattern and in muscular balance.
- Published
- 2004
36. [Devic's optic neuromyelitis: analysis of 7 cases].
- Author
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Sebastián de la Cruz F and López-Dolado E
- Subjects
- Adolescent, Adult, Cervical Vertebrae pathology, Child, Diagnosis, Differential, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Medulla Oblongata pathology, Neuromyelitis Optica drug therapy, Prognosis, Quality of Life, Retrospective Studies, Severity of Illness Index, Neuromyelitis Optica diagnosis
- Abstract
Introduction: Devic's optic neuromyelitis is an unusual condition characterized by the association of unilateral or bilateral optic neuritis and myelitis, both of which are relapsing. Prognosis is usually poor, both for the optic nerve and for the spinal medulla which becomes cavitated. This leads to severe handicap and deterioration in quality of life, except in cases presenting as children., Patients and Methods: We studied seven cases of this condition and describe their clinical and neuroimaging features, cerebrospinal fluid (CSF), evaluation, complications, prognosis and treatment. This data was compared with that in the literature., Results and Conclusions: 1. It is an unusual condition--only 7 cases have been seen at our centre--making up approximately 0.1% of the inflammatory pathology of the spinal cord seen. 2. During the first few hours or days the clinical and radiological findings may not correspond. There may be marked deterioration of CNS function but with normal neuroimaging findings. This may lead to serious problems in diagnosis, which can usually be resolved by repeating the investigation. 3. Differential diagnosis should be made with intramedullary tumors when on neuroimaging there is increased spinal cord diameter with uptake of contrast, and psychiatric disorders when this is normal. 4. The condition usually deteriorates leading to severe disability, since loss of visual acuity is added to the severe spinal cord lesion. 5. Diagnosis should be made by application of the criteria of clinical evolution, imaging and biochemistry defined in the literature, although firm diagnosis can only be made on anatomopathological studies, usually at autopsy.
- Published
- 1999
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