Chasing central nervous system plasticity: the brainstem’s contribution to locomotor recovery in rats with spinal cord injury

Abstract

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.

Bridging the Gap: A Reticulo-Propriospinal Detour Bypassing an Incomplete Spinal Cord Injury

“…The number of ME-positive cells was analyzed by unbiased stereological analysis on every fourth coronal brainstem section using a fluorescence microscope (10ϫ, Axioskop 2, Zeiss). Brain sections were fitted into an atlas-based (Paxinos and Watson, 2009, RRID:nlx_152120) template using defined and prominent anatomical landmarks (facial nerve 7N, inferior olive and pyramidal decussation) (for detailed description, see Zörner et al, 2014), thereby normalizing the analysis to potential tissue atrophy. Retrogradely labeled cells were quantified in four regions of the reticular column: the pontine reticular nucleus, oral part (PnO), the pontine reticular nucleus, caudal part (PnC), the NRG, and the medullary reticular nucleus, ventral part (MdV).…”

“…Compensatory sprouting of spared descending systems was associated with functional recovery after unilateral hemilesions (Rosenzweig et al, 2010). Interestingly, Zörner et al (2014) showed that restricted electrolytic microlesion of the ipsilesional NRG resulted in the reappearance of significant deficits of forelimb and hindlimb locomotion in chronic C4 hemisected rats. The recovered weight support of the ipsilesional forelimb as well as the improved hindpaw clearance and step width seen at 4 months after SCI significantly worsened 2 d after ipsilesional NRG ablation.…”

“…In contrast to previous studies examining compensatory plasticity of unlesioned reticulospinal fibers (Ballermann and Fouad, 2006;Zörner et al, 2014), this study aimed to analyze neuroanatomical adaptations of severed NRG projections and propriospinal fibers upon incomplete SCI in rats using combined anterograde and retrograde neuroanatomical tracings and immunohistochemical stainings. Recovery of locomotor function was assessed by detailed kinematic analysis.…”

Relationship between brainstem neurodegeneration and clinical impairment in traumatic spinal cord injury

“…skilled motor function) (Lemon, 2008), while the dorsal column nuclei and medial lemniscus (Liao et al, 2015) and the periaqueductal grey (PAG) (Benarroch, 2012) are involved in sensory processing and pain modulation. Crucially, structural reorganization of brainstem pathways and nuclei has been associated with functional recovery following experimental SCI (Zaaimi et al, 2012, Zörner et al, 2014). Thus, understanding trauma-induced pathophysiological processes affecting the brainstem pathways and nuclei might offer crucial insights into neurodegeneration and plasticity.…”

Anatomical mechanism of spontaneous recovery in regions caudal to thoracic spinal cord injury lesions in rats

“…However, the CST is not the only descending tract that affects movement and is not be the only projection system that conveys functional recovery (Han et al, 2013; Hurd, Weishaupt & Fouad, 2013). Spared reticulospinal fibers play an important role in the recovery process through spontaneous compensatory sprouting and increases in density after injury; they may also operate caudal to the lesion by enhancing indirect access to reticulospinal commands (Ballermann & Fouad, 2006; Zorner et al, 2014). Therefore, we hypothesize that the nerve fiber circuit underlying repair in this study was composed of CST and reticulospinal fibers and propriospinal neurons.…”