Traumatic spinal cord injury (SCI) elicits an acute inflammatory response which comprises numerous cell populations. It is driven by the immediate response of macrophages and microglia, which triggers activation of genes responsible for the dysregulated microenvironment within the lesion site and in the spinal cord parenchyma immediately adjacent to the lesion. Recently published data indicate that microglia induces astrocyte activation and determines the fate of astrocytes. Conversely, astrocytes have the potency to trigger microglial activation and control their cellular functions. Here we review current information about the release of diverse signaling molecules (pro-inflammatory vs. anti-inflammatory) in individual cell phenotypes (microglia, astrocytes, blood inflammatory cells) in acute and subacute SCI stages, and how they contribute to delayed neuronal death in the surrounding spinal cord tissue which is spared and functional but reactive. In addition, temporal correlation in progressive degeneration of neurons and astrocytes and their functional interactions after SCI are discussed. Finally, the review highlights the time-dependent transformation of reactive microglia and astrocytes into their neuroprotective phenotypes (M2a, M2c and A2) which are crucial for spontaneous post-SCI locomotor recovery. We also provide suggestions on how to modulate the inflammation and discuss key therapeutic approaches leading to better functional outcome after SCI.

Endurance training prior to spinal cord injury (SCI) has a beneficial effect on the activation of signaling pathways responsible for survival, neuroplasticity, and neuroregeneration. It is, however, unclear which training-induced cell populations are essential for the functional outcome after SCI. Adult Wistar rats were divided into four groups: control, six weeks of endurance training, Th9 compression (40 g/15 min), and pretraining + Th9 compression. The animals survived six weeks. Training alone increased the gene expression and protein level of immature CNP-ase oligodendrocytes (~16%) at Th10, and caused rearrangements in neurotrophic regulation of inhibitory GABA/glycinergic neurons at the Th10 and L2 levels, known to contain the interneurons with rhythmogenic potential. Training + SCI upregulated markers for immature and mature (CNP-ase, PLP1) oligodendrocytes by ~13% at the lesion site and caudally, and increased the number of GABA/glycinergic neurons in specific spinal cord regions. In the pretrained SCI group, the functional outcome of hindlimbs positively correlated with the protein levels of CNP-ase, PLP1, and neurofilaments (NF-l), but not with the outgrowing axons (Gap-43) at the lesion site and caudally. These results indicate that endurance training applied before SCI potentiates the repair in damaged spinal cord, and creates a suitable environment for neurological outcome.