Marina Martinez

Sensorimotor training promotes functional recovery and somatosensory cortical map reactivation following cervical spinal cord injury.

Sensorimotor activity has been shown to play a key role in functional recovery after partial spinal cord injury (SCI). Most studies in rodents have focused on the rehabilitation of hindlimb locomotor functions after thoracic or lumbar SCI, whereas forelimb motor and somatosensory abilities after cervical SCI remain largely uninvestigated, despite the high incidence of such injuries in humans. Moreover, little is known about the neurophysiological substrates of training‐induced recovery in supraspinal structures. This study was aimed at evaluating the effects of a training procedure combining both motor and sensory stimulation on behavioral performance and somatosensory cortical map remodeling after cervical (C4–C5) spinal hemisection in rats. This SCI severely impaired both sensory and motor capacities in the ipsilateral limbs. Without training, post‐lesion motor capacities gradually improved, whereas forepaw tactile abilities remained impaired. Consistently, no stimulus‐evoked responses were recorded within the forepaw representational zone in the primary somatosensory (S1) cortex at 2 months after the SCI. However, our data reveal that with training started from the 7th day post‐lesion, a nearly complete recovery (characterized by an early and rapid improvement of motor functions) was associated with a gradual compensation of tactile deficits. Furthermore, the recovery of tactile abilities was correlated with the areal extent of reactivation of S1 cortex forepaw representations. Rehabilitative training promoted post‐lesion adaptive plasticity, probably by enhancing endogenous activity within spared spinal and supraspinal circuits and pathways sustaining sensory and motor functions. This study highlights the beneficial effect of sensorimotor training in motor improvement and its critical influence on tactile recovery after SCI.

A New Rating Scale for Open-Field Evaluation of Behavioral Recovery after Cervical Spinal Cord Injury in Rats

The Basso, Beattie, Bresnahan (BBB) locomotor rating scale has proven a reliable tool to evaluate impairments of hindlimb locomotor skills after thoracic spinal cord injury (SCI). With the increasing use of cervical SCI rat models, there is a critical need to develop scoring scales designed to more precisely examine alteration and recovery of forelimb functions. The main goal of the present study was to elaborate and evaluate a new rating scale for open-field testing of the fore- and hindlimb locomotor functions after cervical SCI. We also assessed the effectiveness of this rating scale for discriminating the functional consequences of dorsolateral (Hdl group), lateral (Hl group), or complete C4 unilateral hemisections (Hc group). Our findings show that the new rating scale can be considered as a sensitive and reliable descriptor of the postoperative time course of deficits affecting differentially the fore- and hindlimb sensorimotor functions following injuries of various severities. This new method provides reproducible data and can be used reliably by non-expert examiners. The proposed rating scale appears to be a useful tool for the assessment of various treatments designed to promote functional recovery after SCI. See online Supplementary Material (scoring spreadsheet and videotape recordings) at www.liebertonline.com.

Recovery of hindlimb locomotion after incomplete spinal cord injury in the cat involves spontaneous compensatory changes within the spinal locomotor circuitry.

After incomplete spinal cord injury (SCI), compensatory changes occur throughout the whole neuraxis, including the spinal cord below the lesion, as suggested by previous experiments using a dual SCI paradigm. Indeed, cats submitted to a lateral spinal hemisection at T10-T11 and trained on a treadmill for 3-14 wk re-expressed bilateral hindlimb locomotion as soon as 24 h after spinalization, a process that normally takes 2-3 wk when a complete spinalization is performed without a prior hemisection. In this study, we wanted to ascertain whether similar effects could occur spontaneously without training between the two SCIs and within a short period of 3 wk in 11 cats. One day after the complete spinalization, 9 of the 11 cats were able to re-express hindlimb locomotion either bilaterally (n = 6) or unilaterally on the side of the previous hemisection (n = 3). In these 9 cats, the hindlimb on the side of the previous hemisection (left hindlimb) performed better than the right side in contrast to that observed during the hemispinal period itself. Cats re-expressing the best bilateral hindlimb locomotion after spinalization had the largest initial hemilesion and the most prominent locomotor deficits after this first SCI. These results provide evidence that 1) marked reorganization of the spinal locomotor circuitry can occur without specific locomotor training and within a short period of 3 wk; 2) the spinal cord can reorganize in a more or less symmetrical way; and 3) the ability to walk after spinalization depends on the degree of deficits and adaptation observed in the hemispinal period.

Incomplete spinal cord injury promotes durable functional changes within the spinal locomotor circuitry

While walking in a straight path, changes in speed result mainly from adjustments in the duration of the stance phase while the swing phase remains relatively invariant, a basic feature of the spinal central pattern generator (CPG). To produce a broad range of locomotor behaviors, the CPG has to integrate modulatory inputs from the brain and the periphery and alter these swing/stance characteristics. In the present work we raise the issue as to whether the CPG can adapt or reorganize in response to a chronic change of supraspinal inputs, as is the case after spinal cord injury (SCI). Kinematic data obtained from six adult cats walking at different treadmill speeds were collected to calculate the cycle and subphase duration at different stages after a first spinal hemisection at T(10) and after a subsequent complete SCI at T(13) respectively aimed at disconnecting unilaterally and then totally the spinal cord from its supraspinal inputs. The results show, first, that the neural control of locomotion is flexible and responsive to a partial or total loss of supraspinal inputs. Second, we demonstrate that a hemisection induces durable plastic changes within the spinal locomotor circuitry below the lesion. In addition, this study gives new insights into the organization of the spinal CPG for locomotion such that phases of the step cycle (swing, stance) can be independently regulated for adapting to speed and also that the CPGs controlling the left and right hindlimbs can, up to a point, be regulated independently.

Chapter 16--spinal plasticity in the recovery of locomotion.

Locomotion is a very robust motor pattern which can be optimized after different types of lesions to the central and/or peripheral nervous system. This implies that several plastic mechanisms are at play to re-express locomotion after such lesions. Here, we review some of the key observations that helped identify some of these plastic mechanisms. At the core of this plasticity is the existence of a spinal central pattern generator (CPG) which is responsible for hindlimb locomotion as observed after a complete spinal cord section. However, normally, the CPG pattern is adapted by sensory inputs to take the environment into account and by supraspinal inputs in the context of goal-directed locomotion. We therefore also review some of the sensory and supraspinal mechanisms involved in the recovery of locomotion after partial spinal injury. We particularly stress a recent development using a dual spinal lesion paradigm in which a first partial spinal lesion is made which is then followed, some weeks later, by a complete spinalization. The results show that the spinal cord below the spinalization has been changed by the initial partial lesion suggesting that, in the recovery of locomotion after partial spinal lesion, plastic mechanisms within the spinal cord itself are very important.

Treadmill training promotes spinal changes leading to locomotor recovery after partial spinal cord injury in cats.

After a spinal hemisection at thoracic level in cats, the paretic hindlimb progressively recovers locomotion without treadmill training but asymmetries between hindlimbs persist for several weeks and can be seen even after a further complete spinal transection at T13. To promote optimal locomotor recovery after hemisection, such asymmetrical changes need to be corrected. In the present study we determined if the locomotor deficits induced by a spinal hemisection can be corrected by locomotor training and, if so, whether the spinal stepping after the complete spinal cord transection is also more symmetrical. This would indicate that locomotor training in the hemisected period induces efficient changes in the spinal cord itself. Sixteen adult cats were first submitted to a spinal hemisection at T10. One group received 3 wk of treadmill training, whereas the second group did not. Detailed kinematic and electromyographic analyses showed that a 3-wk period of locomotor training was sufficient to improve the quality and symmetry of walking of the hindlimbs. Moreover, after the complete spinal lesion was performed, all the trained cats reexpressed bilateral and symmetrical hindlimb locomotion within 24 h. By contrast, the locomotor pattern of the untrained cats remained asymmetrical, and the hindlimb on the side of the hemisection was still deficient. This study highlights the beneficial role of locomotor training in facilitating bilateral and symmetrical functional plastic changes within the spinal circuitry and in promoting locomotor recovery after an incomplete spinal cord injury.

Differential tactile and motor recovery and cortical map alteration after C4-C5 spinal hemisection

After incomplete spinal cord injury (SCI), the adult central nervous system is spontaneously capable of substantial reorganizations that can underlie functional recovery. Most studies have focused on intraspinal reorganizations after SCI and not on the correlative cortical remodeling. Yet, differential studies of neural correlates of the recovery of sensory and motor abilities may be conducted by segregating motor and somatosensory representations in distinct and topologically organized primary cortical areas. This study was aimed at evaluating the effects of a cervical (C4-C5) spinal cord hemisection on sensorimotor performances and electrophysiological maps in primary somatosensory (S1) and motor (M1) cortices in adult rats. After SCI, an enduring loss of the affected forepaw tactile sensitivity was paralleled by the abolishment of somatosensory evoked responses in the deprived forepaw area within the S1 cortex. In contrast, severe motor deficits in unilateral forelimb were partially restored over the first postoperative month, despite remnant deficits in distal movement. The overall M1 map size was drastically reduced in SCI rats relative to intact rats. In the remaining M1 map, the shoulder and elbow movements were over-represented, consistent with the behavioral recovery of proximal joint movements in almost all rats. By contrast, residual wrist representations were observed in M1 maps of half of the rats that did not systematically correlate with a behavioral recovery of these joint movements. This study highlights the differential potential of ascending and descending pathways to reorganize after SCI.

Effect of Locomotor Training in Completely Spinalized Cats Previously Submitted to a Spinal Hemisection

After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later. Cats were not treadmill trained during the hemispinal period. After spinalization, 5 of 9 cats were not trained and served as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week for 3 weeks. Using detailed kinematic analyses, we showed that, without training, the asymmetrical state of locomotion induced by the hemisection was retained durably after the subsequent spinalization. By contrast, training cats after spinalization induced a reversal of the left/right asymmetries, suggesting that new plastic changes occurred within the spinal cord through locomotor training. Moreover, training was shown to improve the kinematic parameters and the performance of the hindlimb on the previously hemisected side. These results indicate that spinal locomotor circuits, previously modified by past experience such as required for adaptation to the hemisection, can remarkably respond to subsequent locomotor training and improve bilateral locomotor kinematics, clearly showing the benefits of locomotor training in the spinal state.

Changes in CNS structures after spinal cord lesions: implications for BMI

It is well established that a spinal circuitry can generate locomotor movements of the hindlimbs in absence of descending supraspinal inputs. This is based, among others, on the observation that after a complete spinalization, cats can walk with the hindlimbs on a treadmill. Does this spinal pattern generator (CPG) also participate in the recovery of locomotion after a partial spinal cord lesion (SCI)? After such SCI, functional reorganization can occur spontaneously along the whole neuraxis, namely the spinal cord circuitry below the lesion (CPG) and in supraspinal structures still partially connected to the spinal cord. This review focuses mainly on the capacity of the spinal and supraspinal structures to reorganize spontaneously after incomplete SCI in animals (rats and cats). BMI approaches to foster recovery of functions after various types of SCI should take into account these changes at the various levels of the CNS.

Sensorimotor Experience Influences Recovery of Forelimb Abilities but Not Tissue Loss after Focal Cortical Compression in Adult Rats

Sensorimotor activity has been shown to play a key role in functional outcome after extensive brain damage. This study was aimed at assessing the influence of sensorimotor experience through subject-environment interactions on the time course of both lesion and gliosis volumes as well as on the recovery of forelimb sensorimotor abilities following focal cortical injury. The lesion consisted of a cortical compression targeting the forepaw representational area within the primary somatosensory cortex of adult rats. After the cortical lesion, rats were randomly subjected to various postlesion conditions: unilateral C5–C6 dorsal root transection depriving the contralateral cortex from forepaw somatosensory inputs, standard housing or an enriched environment promoting sensorimotor experience and social interactions. Behavioral tests were used to assess forelimb placement during locomotion, forelimb-use asymmetry, and forepaw tactile sensitivity. For each group, the time course of tissue loss was described and the gliosis volume over the first postoperative month was evaluated using an unbiased stereological method. Consistent with previous studies, recovery of behavioral abilities was found to depend on post-injury experience. Indeed, increased sensorimotor activity initiated early in an enriched environment induced a rapid and more complete behavioral recovery compared with standard housing. In contrast, severe deprivation of peripheral sensory inputs led to a delayed and only partial sensorimotor recovery. The dorsal rhizotomy was found to increase the perilesional gliosis in comparison to standard or enriched environments. These findings provide further evidence that early sensory experience has a beneficial influence on the onset and time course of functional recovery after focal brain injury.