RESUMEN
The immature central nervous system is recognized as having substantial neuroplastic capacity. In this study, we explored the hypothesis that rehabilitation can exploit that potential and elicit reciprocal walking in nonambulatory children with chronic, severe (i.e., lower extremity motor score < 10/50) spinal cord injuries (SCIs). Seven male subjects (3-12 years of age) who were at least 1-year post-SCI and incapable of discrete leg movements believed to be required for walking, enrolled in activity-based locomotor training (ABLT; clinicaltrials.gov NCT00488280). Six children completed the study. Following a minimum of 49 sessions of ABLT, three of the six children achieved walking with reverse rolling walkers. Stepping development, however, was not accompanied by improvement in discrete leg movements as underscored by the persistence of synergistic movements and little change in lower extremity motor scores. Interestingly, acoustic startle responses exhibited by the three responding children suggested preserved reticulospinal inputs to circuitry below the level of injury capable of mediating leg movements. On the other hand, no indication of corticospinal integrity was obtained with transcranial magnetic stimulation evoked responses in the same individuals. These findings suggest some children who are not predicted to improve motor and locomotor function may have a reserve of adaptive plasticity that can emerge in response to rehabilitative strategies such as ABLT. Further studies are warranted to determine whether a critical need exists to re-examine rehabilitation approaches for pediatric SCI with poor prognosis for any ambulatory recovery.
Asunto(s)
Trastornos del Movimiento , Traumatismos de la Médula Espinal , Humanos , Masculino , Niño , Reflejo de Sobresalto , Caminata/fisiología , Marcha , Extremidad Inferior , Recuperación de la Función , Médula EspinalRESUMEN
Motor rehabilitative training after stroke can improve motor function and promote topographical reorganization of remaining motor cortical movement representations, but this reorganization follows behavioral improvements. A more detailed understanding of the neural bases of rehabilitation efficacy is needed to inform therapeutic efforts to improve it. Using a rat model of upper extremity impairments after ischemic stroke, we examined effects of motor rehabilitative training at the ultrastructural level in peri-infarct motor cortex. Extensive training in a skilled reaching task promoted improved performance and recovery of more normal movements. This was linked with greater axodendritic synapse density and ultrastructural characteristics of enhanced synaptic efficacy that were coordinated with changes in perisynaptic astrocytic processes in the border region between head and forelimb areas of peri-infarct motor cortex. Disrupting synapses and motor maps by infusions of anisomycin (ANI) into anatomically reorganized motor, but not posterior parietal, cortex eliminated behavioral gains from rehabilitative training. In contrast, ANI infusion in the equivalent cortical region of intact animals had no effect on reaching skills. These results suggest that rehabilitative training efficacy for improving manual skills is mediated by synaptic plasticity in a region of motor cortex that, before lesions, is not essential for manual skills, but becomes so as a result of the training. These findings support that experience-driven synaptic structural reorganization underlies functional vicariation in residual motor cortex after motor cortical infarcts.SIGNIFICANCE STATEMENT Stroke is a leading cause of long-term disability. Motor rehabilitation, the main treatment for physical disability, is of variable efficacy. A better understanding of neural mechanisms underlying effective motor rehabilitation would inform strategies for improving it. Here, we reveal synaptic underpinnings of effective motor rehabilitation. Rehabilitative training improved manual skill in the paretic forelimb and induced the formation of special synapse subtypes in coordination with structural changes in astrocytes, a glial cell that influences neural communication. These changes were found in a region that is nonessential for manual skill in intact animals, but came to mediate this skill due to training after stroke. Therefore, motor rehabilitation efficacy depends on synaptic changes that enable remaining brain regions to assume new functions.
Asunto(s)
Astrocitos/patología , Infarto Cerebral/patología , Corteza Motora/patología , Plasticidad Neuronal , Práctica Psicológica , Sinapsis/patología , Animales , Anisomicina/toxicidad , Mapeo Encefálico , Infarto Cerebral/psicología , Modelos Animales de Enfermedad , Miembro Anterior/inervación , Miembro Anterior/fisiopatología , Masculino , Destreza Motora/efectos de los fármacos , Inhibidores de la Síntesis de la Proteína/toxicidad , Ratas , Ratas Long-Evans , Accidente Cerebrovascular/patología , Rehabilitación de Accidente CerebrovascularRESUMEN
Following unilateral stroke, the contralateral (paretic) body side is often severely impaired, and individuals naturally learn to rely more on the nonparetic body side, which involves learning new skills with it. Such compensatory hyper-reliance on the "good" body side, however, can limit functional improvements of the paretic side. In rats, motor skill training with the nonparetic forelimb (NPT) following a unilateral infarct lessens the efficacy of rehabilitative training, and reduces neuronal activation in perilesion motor cortex. However, the underlying mechanisms remain unclear. In the present study, we investigated how forelimb movement representations and synaptic restructuring in perilesion motor cortex respond to NPT and their relationship with behavioral outcomes. Forelimb representations were diminished as a result of NPT, as revealed with intracortical microstimulation mapping. Using transmission electron microscopy and stereological analyses, we found that densities of axodendritic synapses, especially axo-spinous synapses, as well as multiple synaptic boutons were increased in the perilesion cortex by NPT. The synaptic density was negatively correlated with the functional outcome of the paretic limb, as revealed in reaching performance. Furthermore, in animals with NPT, there was dissociation between astrocytic morphological features and axo-spinous synaptic density in perilesion motor cortex, compared with controls. These findings demonstrate that skill learning with the nonparetic limb following unilateral brain damage results in aberrant synaptogenesis, potentially of transcallosal projections, and this seems to hamper the functionality of the perilesion motor cortex and the paretic forelimb.
Asunto(s)
Miembro Anterior/fisiopatología , Lateralidad Funcional/fisiología , Corteza Motora/fisiopatología , Plasticidad Neuronal/fisiología , Accidente Cerebrovascular/patología , Animales , Astrocitos/patología , Astrocitos/ultraestructura , Mapeo Encefálico , Modelos Animales de Enfermedad , Endotelina-1/toxicidad , Terapia por Ejercicio , Masculino , Microscopía Electrónica de Transmisión , Corteza Motora/patología , Corteza Motora/ultraestructura , Destreza Motora/fisiología , Movimiento/fisiología , Fuerza Muscular , Terminales Presinápticos/patología , Terminales Presinápticos/ultraestructura , Ratas , Ratas Long-Evans , Accidente Cerebrovascular/inducido químicamente , Rehabilitación de Accidente Cerebrovascular , Sinapsis/patología , Sinapsis/ultraestructura , Factores de TiempoRESUMEN
Large-scale genomics projects such as the Human Genome Project and the International HapMap Project promise significant advances in the ability to diagnose and treat many conditions, including those with a neurological basis. A major focus of research has emerged in the neurological sciences to elucidate the molecular and genetic basis of various neurological diseases. Indeed, genetic factors are implicated in susceptibility for many neurological disorders, with family history studies providing strong evidence of familial risk for conditions such as stroke, Parkinson's, Alzheimer's, and Huntington's diseases. Heritability studies also suggest a strong genetic contribution to the risk for neurological diseases. Genome-wide association studies are also uncovering novel genetic variants associated with neurological disorders. Whole-genome and exome sequencing are likely to provide novel insights into the genetic basis of neurological disorders. Genetic factors are similarly associated with clinical phenotypes such as symptom severity and progression as well as response to treatment. Specifically, disease progression and functional restoration depend, in part, on the capacity for neural plasticity within residual neural tissues. Furthermore, such plasticity may be influenced in part by the presence of polymorphisms in several genes known to orchestrate neural plasticity including brain-derived neurotrophic factor (BDNF) and Apolipoprotein E. (APOE). It is important for neurorehabilitation therapist practicing in the "genomic era" to be aware of the potential influence of genetic factors during clinical encounters, as advances in molecular sciences are revealing information of critical relevance to the clinical rehabilitation management of individuals with neurological conditions. Video Abstract available (See Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A88) for more insights from the authors.
Asunto(s)
Encéfalo/fisiopatología , Genoma Humano , Enfermedades del Sistema Nervioso/genética , Enfermedades del Sistema Nervioso/rehabilitación , Plasticidad Neuronal/genética , Humanos , Enfermedades del Sistema Nervioso/fisiopatologíaRESUMEN
Movement representations in the motor cortex can reorganize to support motor skill learning during young adulthood. However, little is known about how motor representations change during aging or whether their change is influenced by continued practice of a skill after it is learned. We used intracortical microstimulation to characterize the organization of the forelimb motor cortex in young and aged C57/BL6 mice after short (2-4 weeks) or long (8 weeks) durations of training on a skilled reaching task or control procedures. In young mice, a short duration of reach training increased the area of proximal forelimb movement representations at the expense of distal representations. Following a longer training duration, ratios of proximal to distal movements returned to baseline, even with ongoing practice and skill maintenance. However, lingering changes were evident in thresholds for eliciting distal forelimb movements, which declined over the longer training period. In aged mice, movement representations and movement thresholds failed to change after either duration of training. Furthermore, there was an age-related loss of digit representations and performance decrements on other sensorimotor tests. Nevertheless, in quantitative measures of reaching success, aged mice learned and performed the skilled reaching task at least as well as younger mice. These results indicate that experience-driven topographical reorganization of motor cortex varies with age, as well as time, and is partially dissociable from behavioral performance. They also support an enduring capacity to learn new manual skills during aging, even as more youthful forms of cortical plasticity and sensorimotor function are lost.
Asunto(s)
Envejecimiento/fisiología , Corteza Motora/fisiología , Destreza Motora/fisiología , Plasticidad Neuronal/fisiología , Factores de Edad , Animales , Conducta Animal/fisiología , Miembro Anterior/fisiología , Masculino , Ratones , Movimiento/fisiología , Estimulación Física , Factores de TiempoRESUMEN
The organization of forelimb representation areas of the monkey, cat, and rat motor cortices has been studied in depth, but its characterization in the mouse lags far behind. We used intracortical microstimulation (ICMS) and cytoarchitectonics to characterize the general organization of the C57BL/6 mouse motor cortex, and the forelimb representation in more detail. We found that the forelimb region spans a large area of frontal cortex, bordered primarily by vibrissa, neck, shoulder, and hindlimb representations. It included a large caudal forelimb area, dominated by digit representation, and a small rostral forelimb area, containing elbow and wrist representations. When the entire motor cortex was mapped, the forelimb was found to be the largest movement representation, followed by head and hindlimb representations. The ICMS-defined motor cortex spanned cytoarchitecturally identified lateral agranular cortex (AGl) and also extended into medial agranular cortex. Forelimb and hindlimb representations extended into granular cortex in a region that also had cytoarchitectural characteristics of AGl, consistent with the primary motor-somatosensory overlap zone (OL) characterized in rats. Thus, the mouse motor cortex has homologies with the rat in having 2 forelimb representations and an OL but is distinct in the predominance of digit representations.
Asunto(s)
Mapeo Encefálico , Miembro Anterior/inervación , Ratones/anatomía & histología , Corteza Motora/anatomía & histología , Animales , Estimulación Eléctrica , Masculino , Ratones Endogámicos C57BLRESUMEN
Brain-derived neurotrophic factor (BDNF) is important to brain functions such as plasticity and repair. A single nucleotide polymorphism for this growth factor, val(66)met, is common and associated with decreased activity-dependent BDNF release. The current study evaluated the effects of this polymorphism in relation to human brain motor system function, short-term plasticity, and learning. Functional magnetic resonance imaging (fMRI) scanning during right index finger movement (n = 24) identified activation in a broad sensorimotor network. However, subjects with the polymorphism showed smaller activation volume within several brain regions as compared with subjects without the polymorphism. Repeat fMRI after 25 min of right index finger training found that the 2 genotype groups modulated brain activation differently. In several brain regions, subjects with the polymorphism showed greater activation volume reduction, whereas subjects without the polymorphism showed greater activation volume expansion. On a driving-based motor learning task (independent cohort, n = 29), subjects with the polymorphism showed greater error during short-term learning and poorer retention over 4 days, relative to subjects without the polymorphism. The presence of this BDNF polymorphism is associated with differences in brain motor system function, altered short-term plasticity, and greater error in short-term motor learning. The broader implications of these findings are considered.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/genética , Encéfalo/fisiología , Metionina/genética , Movimiento/fisiología , Polimorfismo de Nucleótido Simple/genética , Valina/genética , Adolescente , Adulto , Análisis de Varianza , Encéfalo/irrigación sanguínea , Mapeo Encefálico , Estudios de Cohortes , Femenino , Dedos/fisiología , Lateralidad Funcional/genética , Genotipo , Humanos , Procesamiento de Imagen Asistido por Computador , Aprendizaje/fisiología , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Oxígeno/sangre , Desempeño Psicomotor/fisiología , Adulto JovenRESUMEN
Motor training can induce profound physiological plasticity within primary motor cortex, including changes in corticospinal output and motor map topography. Using transcranial magnetic stimulation, we show that training-dependent increases in the amplitude of motor-evoked potentials and motor map reorganization are reduced in healthy subjects with a val66met polymorphism in the brain-derived neurotrophic factor gene (BDNF), as compared to subjects without the polymorphism. The results suggest that BDNF is involved in mediating experience-dependent plasticity of human motor cortex.
Asunto(s)
Sustitución de Aminoácidos/genética , Factor Neurotrófico Derivado del Encéfalo/genética , Corteza Motora/fisiología , Destreza Motora/fisiología , Plasticidad Neuronal/genética , Polimorfismo Genético/genética , Adulto , Mapeo Encefálico , Potenciales Evocados Motores/genética , Femenino , Genotipo , Humanos , Aprendizaje/fisiología , Masculino , Metionina/genética , Corteza Motora/anatomía & histología , Movimiento/fisiología , Regeneración Nerviosa/genética , Pruebas Neuropsicológicas , Recuperación de la Función/genética , Estimulación Magnética Transcraneal , Valina/genéticaRESUMEN
There is a lack of consistency among researchers and clinicians in the use of terminology that describes changes in motor ability following neurological injury. Specifically, the terms and definitions of motor compensation and motor recovery have been used in different ways, which is a potential barrier to interdisciplinary communication. This Point of View describes the problem and offers a solution in the form of definitions of compensation and recovery at the neuronal, motor performance, and functional levels within the framework of the International Classification of Functioning model.
Asunto(s)
Trastornos del Movimiento/fisiopatología , Trastornos del Movimiento/rehabilitación , Plasticidad Neuronal/fisiología , Recuperación de la Función/fisiología , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular/fisiopatología , Terminología como Asunto , Evaluación de la Discapacidad , Hemiplejía/complicaciones , Hemiplejía/fisiopatología , Hemiplejía/rehabilitación , Humanos , Comunicación Interdisciplinaria , Trastornos del Movimiento/etiología , Evaluación de Resultado en la Atención de Salud/métodos , Evaluación de Resultado en la Atención de Salud/normas , Accidente Cerebrovascular/complicacionesRESUMEN
Brain plasticity refers to changes in brain function and structure that arise in a number of contexts. One area in which brain plasticity is of considerable interest is recovery from stroke, both spontaneous and treatment-induced. A number of factors influence these poststroke brain events. The current review considers the impact of genetic factors. Polymorphisms in the human genes coding for brain-derived neurotrophic factor (BDNF) and apolipoprotein E (ApoE) have been studied in the context of plasticity and/or stroke recovery and are discussed here in detail. Several other genetic polymorphisms are indirectly involved in stroke recovery through their modulating influences on processes such as depression and pharmacotherapy effects. Finally, new genetic polymorphisms that have not been studied in the context of stroke are proposed as new directions for study. A better understanding of genetic influences on recovery and response to therapy might allow improved treatment after stroke.
Asunto(s)
Plasticidad Neuronal/genética , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/fisiopatología , Animales , Humanos , Proteínas del Tejido Nervioso/fisiología , Recuperación de la Función/genética , Rehabilitación de Accidente CerebrovascularRESUMEN
Tongue exercise programs are used clinically for dysphagia in aged individuals and have been shown to improve lingual strength. However, the neural mechanisms of age-related decline in swallowing function and its association with lingual strength are not well understood. Using an established rat model of aging and tongue exercise, we hypothesized that the motor cortex of aged rats would have a smaller lingual motor map area than young adult rats and would increase in size as a function of tongue exercise. Over 8 weeks, rats either underwent a progressive resistance tongue exercise program (TE), learned the task but did not exercise (trained controls, TC), or were naïve untrained controls (UC). Cortical motor map areas for tongue and jaw were determined using intracortical microstimulation (ICMS). Rats in the TE and TC groups had a significantly larger motor cortex region for the tongue than the UC group. Lingual cortical motor area was not correlated with protrusive tongue force gains and did not differ significantly with age. These results suggest that learning a novel tongue force skill was sufficient to induce plasticity of the lingual motor cortex yet increasing tongue strength with progressive resistance exercise did not significantly expand the lingual motor area beyond the gains that occurred through the skilled learning component.
RESUMEN
The functional organization of adult cerebral cortex is characterized by the presence of highly ordered sensory and motor maps. Despite their archetypical organization, the maps maintain the capacity to rapidly reorganize, suggesting that the neural circuitry underlying cortical representations is inherently plastic. Here we show that the circuitry supporting motor maps is dependent upon continued protein synthesis. Injections of two different protein synthesis inhibitors into adult rat forelimb motor cortex caused an immediate and enduring loss of movement representations. The disappearance of the motor map was accompanied by a significant reduction in synapse number, synapse size, and cortical field potentials and caused skilled forelimb movement impairments. Further, motor skill training led to a reappearance of movement representations. We propose that the circuitry of adult motor cortex is perpetually labile and requires continued protein synthesis in order to maintain its functional organization.
Asunto(s)
Potenciales Evocados Motores/fisiología , Corteza Motora/metabolismo , Proteínas del Tejido Nervioso/biosíntesis , Desempeño Psicomotor/fisiología , Factores de Edad , Animales , Potenciales Evocados Motores/efectos de los fármacos , Masculino , Corteza Motora/efectos de los fármacos , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Inhibidores de la Síntesis de la Proteína/farmacología , Desempeño Psicomotor/efectos de los fármacos , Ratas , Ratas Long-Evans , Sinapsis/efectos de los fármacos , Sinapsis/metabolismoRESUMEN
PURPOSE: This paper reviews 10 principles of experience-dependent neural plasticity and considerations in applying them to the damaged brain. METHOD: Neuroscience research using a variety of models of learning, neurological disease, and trauma are reviewed from the perspective of basic neuroscientists but in a manner intended to be useful for the development of more effective clinical rehabilitation interventions. RESULTS: Neural plasticity is believed to be the basis for both learning in the intact brain and relearning in the damaged brain that occurs through physical rehabilitation. Neuroscience research has made significant advances in understanding experience-dependent neural plasticity, and these findings are beginning to be integrated with research on the degenerative and regenerative effects of brain damage. The qualities and constraints of experience-dependent neural plasticity are likely to be of major relevance to rehabilitation efforts in humans with brain damage. However, some research topics need much more attention in order to enhance the translation of this area of neuroscience to clinical research and practice. CONCLUSION: The growing understanding of the nature of brain plasticity raises optimism that this knowledge can be capitalized upon to improve rehabilitation efforts and to optimize functional outcome.
Asunto(s)
Daño Encefálico Crónico/fisiopatología , Daño Encefálico Crónico/rehabilitación , Lesión Encefálica Crónica/fisiopatología , Lesión Encefálica Crónica/rehabilitación , Plasticidad Neuronal , Animales , Humanos , Recuperación de la FunciónRESUMEN
Rehabilitation-dependent motor recovery after cerebral ischemia is associated with functional reorganization of residual cortical tissue. Recovery is thought to occur when remaining circuitry surrounding the lesion is "retrained" to assume some of the lost function. This reorganization is in turn supported by synaptic plasticity within cortical circuitry and manipulations that promote plasticity may enhance recovery. Activation of the cAMP/CREB pathway is a key step for experience-dependent neural plasticity. Here we examined the effects of the prototypical phosphodiesterase inhibitor 4 (PDE4) rolipram and a novel PDE inhibitor (HT-0712), known to enhance cAMP/CREB signaling and cognitive function, on restoration of motor skill and cortical function after focal cerebral ischemia. Adult male rats were trained on a skilled reaching task to establish a baseline level of motor performance. Intracortical microstimulation was then used to derive high-resolution maps of forelimb movement representations within the caudal forelimb area of motor cortex contralateral to the trained paw. A focal ischemic infarct was created within approximately 30% of the caudal forelimb area. The effects of administering either rolipram or the novel PDE4 inhibitor HT-0712 during rehabilitation on motor recovery and restoration of movement representations within residual motor cortex were examined. Both compounds significantly enhanced motor recovery and induced an expansion of distal movement representations that extended beyond residual motor cortex. The expansion beyond the initial residual cortex was not observed in vehicle injected controls. Furthermore, the motor recovery seen in the HT-0712 animals was dose dependent. Our results suggest that PDE4 inhibitors during motor rehabilitation facilitate behavioral recovery and cortical reorganization after ischemic insult to levels significantly greater than that observed with rehabilitation alone.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/rehabilitación , Inhibidores de Fosfodiesterasa 4 , Inhibidores de Fosfodiesterasa/farmacología , Piperidonas/farmacología , Recuperación de la Función/efectos de los fármacos , Animales , Isquemia Encefálica/fisiopatología , Mapeo Encefálico , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 4/metabolismo , Miembro Anterior/inervación , Masculino , Corteza Motora/enzimología , Corteza Motora/fisiología , Neuronas Motoras/enzimología , Plasticidad Neuronal/efectos de los fármacos , Ratas , Ratas Long-EvansRESUMEN
Motor skill learning, but not mere motor activity, is associated with an increase in both synapse number and glial cell volume within the cerebellar cortex. The increase in synapse number has been shown to persist for at least 4 weeks in the absence of continued training. The present experiment similarly examined how a prolonged interruption in training affects the training-induced increase in astrocytic volume. Adult female rats were randomly allocated to either an acrobatic motor learning condition (AC) or a motor control condition (MC). The AC animals were trained to traverse a complex series of obstacles and each AC animal was pair matched with an MC animal that traversed an obstacle-free runway. These groups were further assigned to one of three training conditions. Animals in the early condition were trained for 10 consecutive days, animals in the delay condition received the same 10 days of training followed by a 28-day period without training, and animals in the continuous condition were trained for the entire 38 days. Unbiased stereological techniques were used to determine that AC animals had a significantly greater volume of astrocytes per Purkinje cell in the cerebellar paramedian lobule than the MC animals, a difference which was reduced (and not statistically detectable) among animals in the delay condition. These findings demonstrate that learning triggers the hypertrophy of astrocytic processes and furthermore that, unlike learning-induced synaptogenesis, astrocytic growth is reduced in the absence of continued training.
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Aprendizaje por Asociación/fisiología , Astrocitos/citología , Corteza Cerebelosa/citología , Destreza Motora/fisiología , Condicionamiento Físico Animal/fisiología , Adaptación Fisiológica , Animales , Aumento de la Célula , Tamaño de la Célula , Femenino , Distribución Aleatoria , Ratas , Ratas Long-Evans , Sinapsis/fisiologíaRESUMEN
Stroke remains the leading cause of adult disability, with upper extremity motor impairments being the most prominent functional deficit in surviving stroke victims. The development of animal models of upper extremity dysfunction after stroke has enabled investigators to examine the neural mechanisms underlying rehabilitation-dependent motor recovery as well as the efficacy of various adjuvant therapies for enhancing recovery. Much of this research has focused on rat models of forelimb motor function after experimentally induced ischemic or hemorrhagic stroke. This article provides a review of several different methods for inducing stroke, including devascularization, photothrombosis, chemical vasoconstriction, and hemorrhagia. We also describe a battery of sensorimotor tasks for assessing forelimb motor function after stroke. The tasks range from measures of gross motor performance to fine object manipulation and kinematic movement analysis, and we offer a comparison of the sensitivity for revealing motor deficits and the amount of time required to administer each motor test. In addition, we discuss several important methodological issues, including the importance of testing on multiple tasks to characterize the nature of the impairments, establishing stable baseline prestroke motor performance measures, dissociating the effects of acute versus chronic testing, and verifying lesion location and size. Finally, we outline general considerations for conducting research using rat models of stroke and the role that these models should play in guiding clinical trials.
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Modelos Animales de Enfermedad , Ratas , Accidente Cerebrovascular/fisiopatología , Extremidad Superior/fisiopatología , Animales , Síntomas Conductuales , Endotelina-1/farmacología , Infarto de la Arteria Cerebral Media , Proyectos de Investigación , Accidente Cerebrovascular/inducido químicamente , Rehabilitación de Accidente CerebrovascularRESUMEN
Ultrasound (US) is known to non-invasively stimulate and modulate brain function; however, the mechanism of action is poorly understood. This study tested US stimulation of rat motor cortex (100 W/cm2, 200 kHz) in combination with epidural cortical stimulation. US directly evoked hindlimb movement. This response occurred even with short US bursts (3 ms) and had short latency (10 ms) and long refractory (3 s) periods. Unexpectedly, the epidural cortical stimulation hindlimb response was not altered during the 3-s refractory period of the US hindlimb response. This finding suggests that the US refractory period is not a general suppression of motor cortex, but rather the recovery time of a US-specific mechanism.
Asunto(s)
Estimulación Eléctrica/métodos , Corteza Motora/fisiología , Ultrasonografía/métodos , Animales , Espacio Epidural , Masculino , Modelos Animales , Ratas , Ratas Sprague-Dawley , Ondas UltrasónicasRESUMEN
The motor cortex and spinal cord possess the remarkable ability to alter structure and function in response to differential motor training. Here we review the evidence that the corticospinal system is not only plastic but that the nature and locus of this plasticity is dictated by the specifics of the motor experience. Skill training induces synaptogenesis, synaptic potentiation, and reorganization of movement representations within motor cortex. Endurance training induces angiogenesis in motor cortex, but it does not alter motor map organization or synapse number. Strength training alters spinal motoneuron excitability and induces synaptogenesis within spinal cord, but it does not alter motor map organization. All three training experiences induce changes in spinal reflexes that are dependent on the specific behavioral demands of the task. These results demonstrate that the acquisition of skilled movement induces a reorganization of neural circuitry within motor cortex that supports the production and refinement of skilled movement sequences. We present data that suggest increases in strength may be mediated by an increased capacity for activation and/or recruitment of spinal motoneurons while the increased metabolic demands associated with endurance training induce cortical angiogenesis. Together these results show the robust pattern of anatomic and physiological plasticity that occurs within the corticospinal system in response to differential motor experience. The consequences of such distributed, experience-specific plasticity for the encoding of motor experience by the motor system are discussed.
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Ejercicio Físico/fisiología , Corteza Motora/fisiología , Movimiento/fisiología , Músculo Esquelético/fisiología , Plasticidad Neuronal/fisiología , Aptitud Física/fisiología , Médula Espinal/fisiología , Potenciales de Acción/fisiología , Adaptación Fisiológica/fisiología , Animales , Humanos , Neuronas Motoras/fisiología , Contracción Muscular/fisiología , Tractos Piramidales/fisiopatologíaRESUMEN
The Human Genome Project and the International HapMap Project have yielded new understanding of the influence of the human genome on health and disease, advancing health care in significant ways. In personalized medicine, genetic factors are used to identify disease risk and tailor preventive and therapeutic regimens. Insight into the genetic bases of cellular processes is revealing the causes of disease and effects of exercise. Many diseases known to have a major lifestyle contribution are highly influenced by common genetic variants. Genetic variants are associated with increased risk for common diseases such as cardiovascular disease and osteoarthritis. Exercise response also is influenced by genetic factors. Knowledge of genetic factors can help clinicians better understand interindividual differences in disease presentation, pain experience, and exercise response. Family health history is an important genetic tool and encourages clinicians to consider the wider client-family unit. Clinicians in this new era need to be prepared to guide patients and their families on a variety of genomics-related concerns, including genetic testing and other ethical, legal, or social issues. Thus, it is essential that clinicians reconsider the role of genetics in the preservation of wellness and risk for disease to identify ways to best optimize fitness, health, or recovery. Clinicians with knowledge of the influence of genetic variants on health and disease will be uniquely positioned to institute individualized lifestyle interventions, thereby fulfilling roles in prevention and wellness. This article describes how discoveries in genomics are rapidly evolving the understanding of health and disease by highlighting 2 conditions: cardiovascular disease and osteoarthritis. Genetic factors related to exercise effects also are considered.
Asunto(s)
Enfermedades Cardiovasculares/genética , Predisposición Genética a la Enfermedad , Genómica , Osteoartritis/genética , Especialidad de Fisioterapia , Enfermedades Cardiovasculares/terapia , Estudio de Asociación del Genoma Completo , Humanos , Actividad Motora/genética , Osteoartritis/terapia , Farmacogenética , Aptitud Física , Polimorfismo de Nucleótido Simple , Medicina de PrecisiónRESUMEN
BACKGROUND: Cortical electrical stimulation of the motor cortex in combination with rehabilitative training (CS/RT) has been shown to enhance motor recovery in animal models of focal cortical stroke, yet in clinical trials, the effects are much less robust. The variability of stroke location in human patient populations that include both cortical and subcortical brain regions may contribute to the failure to find consistent effects clinically. OBJECTIVE: This study sought to determine whether infarct location influences the enhanced motor recovery previously observed in response to CS/RT. The efficacy of CS/RT to promote improvements in motor function was examined in 2 different rat models of stroke that varied the amount and location of cortical and subcortical damage. METHODS: Ischemic infarctions were induced by injecting the vasoconstricting peptide endothelin-1 either (1) onto the middle cerebral artery (MCA) producing damage to the frontal cortex and lateral striatum or (2) into a subcortical region producing damage to the posterior thalamus and internal capsule (subcortical capsular ischemic injury [SCII]). Daily CS/RT or RT alone was then given for 20 days, during which time performance on a skilled reaching task was assessed. RESULTS: Animals with MCA occlusion infarctions exhibited enhanced improvements on a skilled reaching task in response to CS/RT relative to RT alone. No such enhancement was observed in animals with SCII infarctions across the 20 days of treatment. CONCLUSIONS: The efficacy of CS for enhancing motor recovery after stroke may depend in part on the extent and location of the ischemic infarct.