Abstract
Spinal cord injury (SCI) leads to a loss of sensitive and motor functions. Currently, there is no therapeutic intervention offering a complete recovery. Here, we report that repetitive trans-spinal magnetic stimulation (rTSMS) can be a noninvasive SCI treatment that enhances tissue repair and functional recovery. Several techniques including immunohistochemical, behavioral, cells cultures, and proteomics have been performed. Moreover, different lesion paradigms, such as acute and chronic phase following SCI in wild-type and transgenic animals at different ages (juvenile, adult, and aged), have been used. We demonstrate that rTSMS modulates the lesion scar by decreasing fibrosis and inflammation and increases proliferation of spinal cord stem cells. Our results demonstrate also that rTSMS decreases demyelination, which contributes to axonal regrowth, neuronal survival, and locomotor recovery after SCI. This research provides evidence that rTSMS induces therapeutic effects in a preclinical rodent model and suggests possible translation to clinical application in humans.
Highlights
Spinal cord injury (SCI) is an incurable disease which leads to a permanent loss of motor, sensation, and sensory functions below the injury level [1]
We investigated Iba1 expression; Iba1 is a microglial and macrophage-specific marker involved with the membrane ruffling and phagocytosis in activated microglia
Our results showed that Iba1+ area in the repetitive trans-spinal magnetic stimulation (rTSMS) group is significantly decreased by nearly 3 times (Fig. 1N–P), indicating that rTSMS treatment modules spinal scar by reducing fibrosis and inflammation and by increasing astrocytic scar formation (GFAP+, quantified by GFAP-negative area)
Summary
Spinal cord injury (SCI) is an incurable disease which leads to a permanent loss of motor, sensation, and sensory functions below the injury level [1]. The endogenous neural stem cells in the spinal cord can contribute to the scar formation, and secrete neurotrophic factors to prevent neuronal death [10] These quiescent adult neural stem cells in the spinal cord can be activated after SCI, and differentiate into mostly astrocytes and migrate to the injury site to form the core of astrocytic scar [10, 11]. Ependymal cells have been proposed as a therapeutic target for endogenous regeneration after SCI [11, 12] These recent discoveries have led to new starting points for innovative therapies based on the modulation of the cellular populations in the lesion scar. A noninvasive treatment combining the modulation of endogenous cell types is of high interest for SCI therapy
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