Eccentric rehabilitation induces white matter plasticity and sensorimotor recovery in chronic spinal cord injury.

Experience-dependent white matter plasticity offers new potential for rehabilitation-induced recovery after neurotrauma. This first-in-human translational experiment combined myelin water imaging in humans and genetic fate-mapping of oligodendrocyte lineage cells in mice to investigate whether downhill locomotor rehabilitation that emphasizes eccentric muscle actions promotes white matter plasticity and recovery in chronic, incomplete spinal cord injury (SCI). In humans, of 20 individuals with SCI that enrolled, four passed the imaging screen and had myelin water imaging before and after a 12-week (3 times/week) downhill locomotor treadmill training program (SCI + DH).

Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury.

Spinal cord injury (SCI) produces a toxic inflammatory microenvironment that negatively affects plasticity and recovery. Recently, we showed glial activation and peripheral myeloid cell infiltration extending beyond the epicenter through the remote lumbar cord after thoracic SCI. The presence and role of infiltrating monocytes is important, especially in the lumbar cord where locomotor central pattern generators are housed.

Unique Sensory and Motor Behavior in Thy1-GFP-M Mice before and after Spinal Cord Injury.

Sensorimotor recovery after spinal cord injury (SCI) is of utmost importance to injured individuals and will rely on improved understanding of SCI pathology and recovery. Novel transgenic mouse lines facilitate discovery, but must be understood to be effective. The purpose of this study was to characterize the sensory and motor behavior of a common transgenic mouse line (Thy1-GFP-M) before and after SCI.

Adaptation of the Basso-Beattie-Bresnahan locomotor rating scale for use in a clinical model of spinal cord injury in dogs.

Background: Naturally occurring acute spinal cord injury (SCI) in pet dogs provides an important clinical animal model through which to confirm and extend findings from rodent studies; however, validated quantitative outcome measures for dogs are limited.

New Method: We adapted the Basso Beattie Bresnahan (BBB) scale for use in a clinical dog model of acute thoracolumbar SCI. Based on observation of normal dogs, modifications were made to account for species differences in locomotion.

Quantitative evaluation of 3D mouse behaviors and motor function in the open-field after spinal cord injury using markerless motion tracking.

Thousands of scientists strive to identify cellular mechanisms that could lead to breakthroughs in developing ameliorative treatments for debilitating neural and muscular conditions such as spinal cord injury (SCI). Most studies use rodent models to test hypotheses, and these are all limited by the methods available to evaluate animal motor function. This study's goal was to develop a behavioral and locomotor assessment system in a murine model of SCI that enables quantitative kinematic measurements to be made automatically in the open-field by applying markerless motion tracking approaches.

Elevated MMP-9 in the lumbar cord early after thoracic spinal cord injury impedes motor relearning in mice.

Spinal cord injury results in distant pathology around putative locomotor networks that may jeopardize the recovery of locomotion. We previously showed that activated microglia and increased cytokine expression extend at least 10 segments below the injury to influence sensory function. Matrix metalloproteinase-9 (MMP-9) is a potent regulator of acute neuroinflammation.

Characterization of recovered walking patterns and motor control after contusive spinal cord injury in rats.

Currently, complete recovery is unattainable for most individuals with spinal cord injury (SCI). Instead, recovery is typically accompanied by persistent sensory and motor deficits. Restoration of preinjury function will likely depend on improving plasticity and integration of these impaired systems.

Acute and chronic tactile sensory testing after spinal cord injury in rats.

Spinal cord injury (SCI) impairs sensory systems causing allodynia. To identify cellular and molecular causes of allodynia, sensitive and valid sensory testing in rat SCI models is needed. However, until recently, no single testing approach had been validated for SCI so that standardized methods have not been implemented across labs.

Validity of acute and chronic tactile sensory testing after spinal cord injury in rats.

Spinal cord injury (SCI) impairs sensory systems causing allodynia. Measuring the development of allodynia in rodent models of SCI is challenging due to spinal shock and marked motor impairments. Assessment of SCI-induced allodynia is not standardized across labs, making interpretation of results difficult.

Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats.

Spinal cord injury (SCI) impairs sensory systems causing chronic allodynia. Mechanisms underlying neuropathic pain have been more extensively studied following peripheral nerve injury (PNI) than after central trauma. Microglial activation, pro-inflammatory cytokine production and activation of p38 MAP kinase pathways may induce at-level allodynia following PNI.

Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains.

Genetically engineered mice are used extensively to examine molecular responses to spinal cord injury (SCI). Inherent strain differences may confound behavioral outcomes; therefore, behavioral characterization of several strains after SCI is warranted. The Basso, Beattie, Bresnahan Locomotor Rating Scale (BBB) for rats has been widely used for SCI mice, but may not accurately reflect their unique recovery pattern.

Stepwise motor and all-or-none sensory recovery is associated with nonlinear sparing after incremental spinal cord injury in rats.

Spinal cord injury (SCI) causes motor and sensory deficits that impair functional performance. While more functional recovery occurs with greater white matter sparing (WMS), it is unclear which locomotor features are more vulnerable to SCI than others, if recovery of certain features depends on specific amounts of WMS, and whether motor recovery patterns differ from sensory recovery. Locomotor and sensory recovery after graded contusive SCI with cord displacements of 0.

Passive or active immunization with myelin basic protein impairs neurological function and exacerbates neuropathology after spinal cord injury in rats.

Myelin-reactive T-cells are activated by traumatic spinal cord injury (SCI) in rodents and humans. Despite the historical association of these cells with experimental and clinical neuropathology, recent data suggest a neuroprotective role for myelin-reactive T-cells. Because of the biological and therapeutic implications of these findings, we attempted to reproduce the original neuroprotective vaccine protocols in a model of rat SCI.