The alarmin interleukin-1α triggers secondary degeneration through reactive astrocytes and endothelium after spinal cord injury

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

Corticospinal Responses Following Gait-Specific Training in Stroke Survivors: A Systematic Review

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