Remote damage after spinal cord injury

Abstract

After spinal cord injury pathological changes in the lesion site and adjacent segments are described in detail. Data are accumulating on the tissue response in the areas of the spinal cord and even the brain distant from the epicentre of spinal cord injury. The concept of plasticity and post-traumatic responses in remote lumbar regions, which contain a specific circuits of interneurons known as the central pattern generator, is particularly important for the recovery of motor function. Among the factors influencing the plasticity of neuronal connections and regenerative potential in the area remote from the lesion epicentre, myeloid infiltration, microglial reactivity, neuroinflammation, and molecular rearrangements of the extracellular matrix are only beginning to be systematically studied. After thoracic spinal cord injury rapid responses develop in the lumbar cord that are characteristic of disintegration of the axons of the descending tracts. These shifts are accompanied by glial reactivity, synapse elimination, imbalance between excitation and inhibition, and disruption of connections in neural networks. This severity of these remote changes depends on the type and severity of the injury, which determines the different involvement and degree of destruction of the descending motor pathways. The review presents an analysis of experimental data on the responses and reorganization of the neural network in the lumbar spinal cord after injury in the proximal regions. The lesional biomarkers are of particular interest as a possible cause of pathological changes in distant areas. These molecules are released from dying cells at the epicenter of injury, appear in the cerebrospinal fluid, and acting as injury-associated molecular patterns and alarmins, can exert a neurotoxic effect in areas remote from the epicenter of injury.