Anatomical plasticity such as fibre growth and the formation of new connections in the cortex and spinal cord is one known mechanism mediating functional recovery after damage to the central nervous system. Little is known about anatomical plasticity in the brainstem, which contains key locomotor regions. We compared changes of the spinal projection pattern of the major descending systems following a cervical unilateral spinal cord hemisection in adult rats. As in humans (Brown-Séquard syndrome), this type of injury resulted in a permanent loss of fine motor control of the ipsilesional fore- and hindlimb, but for basic locomotor functions substantial recovery was observed. Antero- and retrograde tracings revealed spontaneous changes in spinal projections originating from the reticular formation, in particular from the contralesional gigantocellular reticular nucleus: more reticulospinal fibres from the intact hemicord crossed the spinal midline at cervical and lumbar levels. The intact-side rubrospinal tract showed a statistically not significant tendency towards an increased number of midline crossings after injury. In contrast, the corticospinal and the vestibulospinal tract, as well as serotonergic projections, showed little or no side-switching in this lesion paradigm. Spinal adaptations were accompanied by modifications at higher levels of control including side-switching of the input to the gigantocellular reticular nuclei from the mesencephalic locomotor region. Electrolytic microlesioning of one or both gigantocellular reticular nuclei in behaviourally recovered rats led to the reappearance of the impairments observed acutely after the initial injury showing that anatomical plasticity in defined brainstem motor networks contributes significantly to functional recovery after injury of the central nervous system.

Anatomically incomplete spinal cord injuries are often followed by considerable functional recovery in patients and animal models, largely because of processes of neuronal plasticity. In contrast to the corticospinal system, where sprouting of fibers and rearrangements of circuits in response to lesions have been well studied, structural adaptations within descending brainstem pathways and intraspinal networks are poorly investigated, despite the recognized physiological significance of these systems across species. In the present study, spontaneous neuroanatomical plasticity of severed bulbospinal systems and propriospinal neurons was investigated following unilateral C4 spinal hemisection in adult rats. Injection of retrograde tracer into the ipsilesional segments C3-C4 revealed a specific increase in the projection from the ipsilesional gigantocellular reticular nucleus in response to the injury. Substantial regenerative fiber sprouting of reticulospinal axons above the injury site was demonstrated by anterograde tracing. Regrowing reticulospinal fibers exhibited excitatory, vGLUT2-positive varicosities, indicating their synaptic integration into spinal networks. Reticulospinal fibers formed close appositions onto descending, double-midline crossing C3-C4 propriospinal neurons, which crossed the lesion site in the intact half of the spinal cord and recrossed to the denervated cervical hemicord below the injury. These propriospinal projections around the lesion were significantly enhanced after injury. Our results suggest that severed reticulospinal fibers, which are part of the phylogenetically oldest motor command system, spontaneously arborize and form contacts onto a plastic propriospinal relay, thereby bypassing the lesion. These rearrangements were accompanied by substantial locomotor recovery, implying a potential physiological relevance of the detour in restoration of motor function after spinal injury.

Rodents are frequently used to model damage and diseases of the central nervous system (CNS) that lead to functional deficits. Impaired locomotor function is currently evaluated by using scoring systems or biomechanical measures. These methods often suffer from limitations such as subjectivity, nonlinearity and low sensitivity, or focus on a few very restricted aspects of movement. Thus, full quantitative profiles of motor deficits after CNS damage are lacking. Here we report the detailed characterization of locomotor impairments after applying common forms of CNS damage in rodents. We obtained many objective and quantitative readouts from rats with either spinal cord injuries or strokes and from transgenic mice (Epha4−/−) during skilled walking, overground walking, wading and swimming, resulting in model-specific locomotor profiles. Our testing and analysis method enables comprehensive assessment of locomotor function in rodents and has broad application in various fields of life science research.

Gait dysfunction is a common and relevant symptom in multiple sclerosis (MS). This study aimed to profile gait pathology in gait-impaired patients with MS using comprehensive 3D gait analysis and clinical walking tests. Thirty-seven patients with MS walked on the treadmill at their individual, sustainable speed while 20 healthy control subjects walked at all the different patient’s paces, allowing for comparisons independent of walking velocity. Kinematic analysis revealed pronounced restrictions in knee and ankle joint excursion, increased gait variability and asymmetry along with impaired dynamic stability in patients. The most discriminative single gait parameter, differentiating patients from controls with an accuracy of 83.3% (χ2 test; p = 0.0001), was reduced knee range of motion. Based on hierarchical cluster and principal component analysis, three principal pathological gait patterns were identified: a spastic-paretic, an ataxia-like, and an unstable gait. Follow-up assessments after 1 year indicated deterioration of walking function, particularly in patients with spastic-paretic gait patterns. Our findings suggest that impaired knee/ankle control is common in patients with MS. Personalised gait profiles and clustering algorithms may be promising tools for stratifying patients and to inform patient-tailored exercise programs. Responsive, objective outcome measures are important for monitoring disease progression and treatment effects in MS trials.