Comparison of the effects of two therapeutic strategies based on olfactory ensheathing cell transplantation and repetitive magnetic stimulation after spinal cord injury in female mice

Abstract

Spinal cord injury (SCI) is a debilitating condition, which leads to a permanent loss of functions below the injury site. The events which take place after SCI are characterized by cellular death, release of inhibitory factors, and inflammation. Many therapies have been studied to cure SCI, among them magnetic stimulation aims to reduce the secondary damages in particular by decreasing apoptosis, while, cellular transplantation promotes neuroregeneration by enhancing axonal regrowth. In the present study, we compared individually primary olfactory ensheathing cell (OEC) transplantation and repetitive trans‐spinal magnetic stimulation (rTSMS) and then, we combined these two therapeutic approaches on tissue repair and functional recovery after SCI. To do so, SCIs were performed at Th10 level on female C57BL/6 mice, which were randomized into four groups: SCI, SCI + primary bOECs, SCI + STM, SCI + primary bulbar olfactory ensheathing cells (bOECs) + stimulation (STM). On these animals bioluminescence, immunohistological, and behavioral experiments were performed after SCI. Our results show that rTSMS has beneficial effect on the modulation of spinal scar by reducing fibrosis, demyelination, and microglial cell activation and by increasing the astroglial component of the scar, while, primary bOEC transplantation decreases microglial reactivity. At the opposite, locotronic experiments show that both treatments induce functional recovery. We did not observed any additional effect by combining the two therapeutic approaches. Taken together, the present study indicates that primary bOEC transplantation and rTSMS treatment act through different mechanisms after SCI to induce functional recovery. In our experimental paradigm, the combination of the two therapies does not induce any additional benefit.

Repetitive Trans Spinal Magnetic Stimulation Improves Functional Recovery and Tissue Repair in Contusive and Penetrating Spinal Cord Injury Models in Rats

“…Indeed, the effects of rTSMS were measured first in a penetrating injury model in which the spinal cord was transected with a needle. This model was chosen because it was used initially in our princeps studies in mice [ 9 , 16 ]. As described in mice, in this model, rTSMS treatment enhances functional recovery and modulates the lesion scar in rats.…”

“…Surgical Procedure In order to assess the effects of the rTSMS treatment and to compare them to those described in mice, first we performed penetrating SCI by using a 25-gauge needle in rats, as described previously [9,16].…”

“…Immunohistochemistry was performed as described previously [ 9 , 16 ]. The following primary antibodies were used: rabbit anti-platelet-derived growth factorβ (PDGFRβ, Abcam, Cambridge, UK, ab32570), mouse anti-glial fibrillary acidic protein (GFAP Cy3-conjugated Sigma-Aldrich, C9205 and GFAP unconjugated Sigma-Aldrich, G3893), rabbit anti-ionized calcium-binding adapter molecule 1 (Iba1, Wako, 019-19741, Osaka, Japan) and mouse anti-neurofilament 200 kD (NF200, Millipore, Burlington, MA, USA, MAB5256).…”

“…Recently, our research group reported that repetitive trans-spinal magnetic stimulation (rTSMS) can be used as a non-invasive treatment after SCI. Our study demonstrates that rTSMS modulates the spinal scar and enhances axonal regrowth and locomotor recoveries [ 9 , 16 , 17 ]. These experiments were conducted in a mouse model, and SCI was performed by complete transection.…”

Plasticity of the Injured Spinal Cord

“…Noninvasive approaches such as magnetic stimulation have also been investigated recently to manipulate the cellular populations which compose the scar after SCI. In effect, in recent studies repetitive trans-spinal magnetic stimulation (rTSMS), a noninvasive therapy, has been applied to a complete transection model in mice [45,46]. In this model, rTSMS was applied 10 min per day for 14 days after SCI.…”