Abstract
Spinal cord injury (SCI) is an incurable condition in which the brain is disconnected partially or completely from the periphery. Mainly, SCIs are traumatic and are due to traffic, domestic or sport accidents. To date, SCIs are incurable and, most of the time, leave the patients with a permanent loss of sensitive and motor functions. Therefore, for several decades, researchers have tried to develop treatments to cure SCI. Among them, recently, our lab has demonstrated that, in mice, repetitive trans-spinal magnetic stimulation (rTSMS) can, after SCI, modulate the lesion scar and can induce functional locomotor recovery non-invasively. These results are promising; however, before we can translate them to humans, it is important to reproduce them in a more clinically relevant model. Indeed, SCIs do not lead to the same cellular events in mice and humans. In particular, SCIs in humans induce the formation of cystic cavities. That is why we propose here to validate the effects of rTSMS in a rat animal model in which SCI leads to the formation of cystic cavities after penetrating and contusive SCI. To do so, several techniques, including immunohistochemical, behavioral and MRI, were performed. Our results demonstrate that rTSMS, in both SCI models, modulates the lesion scar by decreasing the formation of cystic cavities and by improving axonal survival. Moreover, rTSMS, in both models, enhances functional locomotor recovery. Altogether, our study describes that rTSMS exerts positive effects after SCI in rats. This study is a further step towards the use of this treatment in humans.
Highlights
Spinal cord injury (SCI) is a debilitating condition which can lead to a permanent loss of motor and sensitive functions
Locotronic results demonstrate that 15 days after SCI, repetitive trans-spinal magnetic stimulation (rTSMS) treatment did not enhance locomotor abilities (Figure 2A-C), there is no significant difference between SCI and Stm groups at this time point (Figure 2A-C)
60 days after SCI, our results reveal that rTSMS modulates the spinal scar by decreasing the GFAP negative (GFAP-) area (Figure 4G)
Summary
Spinal cord injury (SCI) is a debilitating condition which can lead to a permanent loss of motor and sensitive functions. At the same time the initial traumatic injury leads to neuronal and oligodendroglial death 2,4 These cellular events conduct to the formation of a spinal scar composed of a fibrotic core presents into the lesion epicenter and of an astroglial scar located at the border of the lesion 5–7. In rats and Humans, the fibrotic core presents at the lesion epicenter of the spinal scar in mice is replaced progressively by cystic cavities within weeks to months after SCI 14. That is why it can be of primary importance before to translate an innovative therapy to clinical in Humans to validate it in mice and in rats. In Humans SCI are mainly due to contusive injury whereas in preclinical models, SCI are oftenly penetrating because this model is reproducible and does not require specific apparatus 15
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