ABSTRACT
Corticospinal excitability is subject to alterations after stroke. While the reversal of these alterations has been proposed as an underlying mechanism for improved walking capacity after gait-specific training, this has not yet been clearly demonstrated. Therefore, the objective of this review is to evaluate the effect of gait-specific training on corticospinal excitability in stroke survivors. We conducted an electronic database search in four databases (i.e., Medline, Embase, CINAHL and Web of Science) in June 2022. Two authors screened in an independent way all the studies and selected those that investigated the effect of gait-specific training on variables such as motor-evoked potential amplitude, motor threshold, map size, latency, and corticospinal silent period in stroke survivors. Nineteen studies investigating the effect of gait-specific training on corticospinal excitability were included. Some studies showed an increased MEP amplitude (7/16 studies), a decreased latency (5/7studies), a decreased motor threshold (4/8 studies), an increased map size (2/3 studies) and a decreased cortical silent period (1/2 study) after gait-specific training. No change has been reported in terms of short interval intracortical inhibition after training. Five studies did not report any significant effect after gait-specific training on corticospinal excitability. The results of this systematic review suggest that gait-specific training modalities can drive neuroplastic adaptation among stroke survivors. However, given the methodological disparity of the included studies, additional clinical trials of better methodological quality are needed to establish conclusions. The results of this review can therefore be used to develop future studies to better understand the effects of gait-specific training on the central nervous system.
Subject(s)
Motor Cortex , Stroke Rehabilitation , Stroke , Humans , Motor Cortex/physiology , Evoked Potentials, Motor/physiology , Exercise Therapy/methods , Gait/physiologyABSTRACT
Spinal cord injury (SCI) triggers neuroinflammation, and subsequently secondary degeneration and oligodendrocyte (OL) death. We report that the alarmin interleukin (IL)-1α is produced by damaged microglia after SCI. Intra-cisterna magna injection of IL-1α in mice rapidly induces neutrophil infiltration and OL death throughout the spinal cord, mimicking the injury cascade seen in SCI sites. These effects are abolished through co-treatment with the IL-1R1 antagonist anakinra, as well as in IL-1R1-knockout mice which demonstrate enhanced locomotor recovery after SCI. Conditional restoration of IL-1R1 expression in astrocytes or endothelial cells (ECs), but not in OLs or microglia, restores IL-1α-induced effects, while astrocyte- or EC-specific Il1r1 deletion reduces OL loss. Conditioned medium derived from IL-1α-stimulated astrocytes results in toxicity for OLs; further, IL-1α-stimulated astrocytes generate reactive oxygen species (ROS), and blocking ROS production in IL-1α-treated or SCI mice prevented OL loss. Thus, after SCI, microglia release IL-1α, inducing astrocyte- and EC-mediated OL degeneration.
Subject(s)
Interleukin-1alpha , Spinal Cord Injuries , Alarmins/metabolism , Animals , Astrocytes/metabolism , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Endothelial Cells/metabolism , Endothelium/metabolism , Interleukin 1 Receptor Antagonist Protein , Interleukin-1alpha/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Microglia/metabolism , Reactive Oxygen Species/metabolism , Spinal Cord/metabolism , Spinal Cord Injuries/metabolismABSTRACT
Chronic pain is a major comorbidity of chronic inflammatory diseases. Here, we report that the cytokine IL-1ß, which is abundantly produced during multiple sclerosis (MS), arthritis (RA), and osteoarthritis (OA) both in humans and in animal models, drives pain associated with these diseases. We found that the type 1 IL-1 receptor (IL-1R1) is highly expressed in the mouse and human by a subpopulation of TRPV1+ dorsal root ganglion neurons specialized in detecting painful stimuli, termed nociceptors. Strikingly, deletion of the Il1r1 gene specifically in TRPV1+ nociceptors prevented the development of mechanical allodynia without affecting clinical signs and disease progression in mice with experimental autoimmune encephalomyelitis and K/BxN serum transfer-induced RA. Conditional restoration of IL-1R1 expression in nociceptors of IL-1R1-knockout mice induced pain behavior but did not affect joint damage in monosodium iodoacetate-induced OA. Collectively, these data reveal that neuronal IL-1R1 signaling mediates pain, uncovering the potential benefit of anti-IL-1 therapies for pain management in patients with chronic inflammatory diseases.
Subject(s)
Inflammation/metabolism , Inflammation/pathology , Neurons/metabolism , Pain/metabolism , Pain/pathology , Receptors, Interleukin-1/metabolism , Adult , Aged , Animals , Arthritis, Rheumatoid/pathology , Behavior, Animal , Chronic Disease , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/pathology , Female , Ganglia, Spinal/metabolism , Ganglia, Spinal/pathology , Hindlimb/pathology , Humans , Hyperalgesia/complications , Hyperalgesia/pathology , Inflammation/complications , Interleukin-1beta/metabolism , Knee Joint/pathology , Male , Mice, Inbred C57BL , Middle Aged , Myeloid Cells/metabolism , Neurons/pathology , Nociceptors/metabolism , Osteoarthritis , Pain/complications , Receptors, Interleukin-1/deficiency , Receptors, Interleukin-1/genetics , Sensory Receptor Cells/metabolism , Spinal Nerve Roots/metabolism , Spinal Nerve Roots/pathology , TRPV Cation Channels/metabolismABSTRACT
The role of microglia in spinal cord injury (SCI) remains poorly understood and is often confused with the response of macrophages. Here, we use specific transgenic mouse lines and depleting agents to understand the response of microglia after SCI. We find that microglia are highly dynamic and proliferate extensively during the first two weeks, accumulating around the lesion. There, activated microglia position themselves at the interface between infiltrating leukocytes and astrocytes, which proliferate and form a scar in response to microglia-derived factors, such as IGF-1. Depletion of microglia after SCI causes disruption of glial scar formation, enhances parenchymal immune infiltrates, reduces neuronal and oligodendrocyte survival, and impairs locomotor recovery. Conversely, increased microglial proliferation, induced by local M-CSF delivery, reduces lesion size and enhances functional recovery. Altogether, our results identify microglia as a key cellular component of the scar that develops after SCI to protect neural tissue.
