After spinal cord injury (SCI), destruction of the blood spinal cord barrier (BSCB) results in in ltration of blood cells, such as neutrophils and macrophages, leading to permanent neurological dysfunction.Previous studies have shown that human bone marrow mesenchymal stem cell (BMSC)-derived exosomes have a bene cial neuroprotective effect in SCI models. However, whether BMSC-Exos contribute to the integrity of the BSCB has not been clari ed. The purpose of this study was to investigate the mechanism of BMSC-Exo-induced changes in the permeability of the BSCB after SCI. Here, we showed that BMSC-Exos can inhibit BSCB permeability damage and improve spontaneous repair in a SCI model. Importantly, tissue inhibitors of matrix metalloproteinases 2 (TIMP2) were shown to play an important role in the functions of BMSCS-Exos by inhibiting the matrix metalloproteinase (MMP) pathway, thereby mitigating the reduction in cell junction proteins. Moreover, the ability of BMSC-Exos was signi cantly attenuated when TIMP2 was inhibited by siRNA. This proof-of-principle study demonstrates that BMSC-Exos can preserve the integrity of the BSCB and improve functional recovery after SCI through the TIMP2/MMP signaling pathway.

Lactobacillus rhamnoides, a human intestinal colonizer, can act through various pathways to induce microglia/macrophages to produce cytokines and to polarize microglia/macrophages to different phenotypes to reduce the inflammatory response. In this article, we evaluated the treatment potential of the Lactobacillus rhamnoides GG conditioned medium (LGG-CM) in rat model with SCI (acute spinal cord injury), including functional, neurophysiological, and histological outcomes and the underlying neuroprotective mechanisms. In our experiment, LGG-CM (30 mg/kg) was injected directly into the injury site in rats immediately after SCI. Measured by the BBB scale (Basso, Beattie, and Bresnahan locomotor rating scale) and inclined plane test, rats in the LGG-CM-treated group showed better locomotor scores. Moreover, compared to the vehicle treatment group, LGG-CM increased the mRNA level of the M2 marker (CD206), and decreased that of the M1 marker (iNOS). Western blot assays showed that LGG-CM-treated SCI rats had a higher grayscale ratio of p65 and a lower ratio of p-IκBα/IκBα. Our study shows that local injection of LGG-CM after acute SCI can inhibit inflammatory responses and improve motor function recovery. These effects may be related with the inhibition to the NF-κB (The nuclear factor-kappa B) signal pathway which leads to M2 microglia/macrophage polarization.

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