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Spinal cord injury (SCI) is a global medical problem with high disability and mortality rates. At present, the diagnosis and treatment of SCI are still lacking. Spinal cord injury has a complex etiology, lack of diagnostic methods, poor treatment effect and other problems, which lead to the difficulty of spinal cord regeneration and repair, and poor functional recovery. Recent studies have shown that gene expression plays an important role in the regulation of SCI repair. MicroRNAs (miRNAs) are non-coding RNA molecules that target mRNA expression in order to silence, translate, or interfere with protein synthesis. Secondary damage, such as oxidative stress, apoptosis, autophagy, and inflammation, occurs after SCI, and differentially expressed miRNAs contribute to these events. This article reviews the pathophysiological mechanism of miRNAs in secondary injury after SCI, focusing on the mechanism of miRNAs in secondary neuroinflammation after SCI, so as to provide new ideas and basis for the clinical diagnosis and treatment of miRNAs in SCI. The mechanisms of miRNAs in neurological diseases may also make them potential biomarkers and therapeutic targets for spinal cord injuries.

Background: Induced pluripotent stem cells-derived exosomes (iPSCs-Exo) can effectively treat spinal cord injury (SCI) in mice. But the role of iPSCs-Exo in SCI mice and its molecular mechanisms remain unclear. This research intended to study the effects and molecular mechanism of iPSCs-Exo in SCI mice models.Methods: The feature of iPSCs-Exo was determined by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA), and western blot. The effects of iPSCs-Exo in the SCI mice model were evaluated by Basso Mouse Scale (BMS) scores and H&E staining. The roles of iPSCs-Exo and miR-199b-5p in LPS-treated BMDM were verified by immunofluorescence, RT-qPCR, and Cytokine assays. The target genes of miR-199b-5p were identified, and the function of miR-199b-5p and its target genes on LPS-treated BMDM was explored by recuse experiment.Results: iPSCs-Exo improved motor function in SCI mice model in vivo, shifted the polarization from M1 macrophage to M2 phenotype, and regulated related inflammatory factors expression to accelerate the SCI recovery in LPS-treated BMDM in vitro. Meanwhile, miR-199b-5p was a functional player of iPSCs-Exo, which could target hepatocyte growth factor (Hgf). Moreover, miR-199b-5p overexpression polarized M1 macrophage into M2 phenotype and promoted neural regeneration in SCI. The rescue experiments confirmed that miR-199b-5p induced macrophage polarization and SCI recovery by regulating Hgf and Phosphoinositide 3-kinase (PI3K) signaling pathways.Conclusion: The miR-199b-5p-bearing iPSCs-Exo might become an effective method to treat SCI.

The primary traumatic event that causes spinal cord injury (SCI) is followed by a progressive secondary injury featured by vascular disruption and ischemia, inflammatory responses and the release of cytotoxic debris, which collectively add to the hostile microenvironment of the lesioned cord and inhibit tissue regeneration and functional recovery. In a previous study, we reported that fecal microbiota transplantation (FMT) promotes functional recovery in a contusion SCI mouse model; yet whether and how FMT treatment may impact the microenvironment at the injury site are not well known. In the current study, we examined individual niche components and investigated the effects of FMT on microcirculation, inflammation and trophic factor secretion in the spinal cord of SCI mice. FMT treatment significantly improved spinal cord tissue sparing, vascular perfusion and pericyte coverage and blood-spinal cord-barrier (BSCB) integrity, suppressed the activation of microglia and astrocytes, and enhanced the secretion of neurotrophic factors. Suppression of inflammation and upregulation of trophic factors, jointly, may rebalance the niche homeostasis at the injury site and render it favorable for reparative and regenerative processes, eventually leading to functional recovery. Furthermore, microbiota metabolic profiling revealed that amino acids including β-alanine constituted a major part of the differentially detected metabolites between the groups. Supplementation of β-alanine in SCI mice reduced BSCB permeability and increased the number of surviving neurons, suggesting that β-alanine may be one of the mediators of FMT that participates in the modulation and rebalancing of the microenvironment at the injured spinal cord.

Increased mechanical stress after spinal cord injury (SCI) expands the scope of nerve tissue damage and exacerbates nerve function defects. Surgical decompression after SCI is a conventional therapeutic strategy and has been proven to have neuroprotective effects. However, the mechanisms of the interaction between mechanical stress and neurons are currently unknown. In this study, we monitored intramedullary pressure (IMP) and investigated the therapeutic benefit of decompression (including durotomy and piotomy) after injury and its underlying mechanisms in SCI. We found that decreased IMP promotes the generation and degradation of LC3 II, promotes the degradation of p62 and enhances autophagic flux to alleviate apoptosis. The lysosomal dysfunction was reduced after decompression. Piotomy was better than durotomy for the histological repair of spinal cord tissue after SCI. However, the autophagy‐lysosomal pathway inhibitor chloroquine (CQ) partially reversed the apoptosis inhibition caused by piotomy after SCI, and the structural damage was also aggravated after CQ administration. An antibody microarray analysis showed that decompression may reverse the up‐regulated abundance of p‐PI3K, p‐AKT and p‐mTOR caused by SCI. Our findings may contribute to a better understanding of the mechanism of decompression and the effects of mechanical stress on autophagy after SCI.

Spinal cord injury (SCI) disturbs the autonomic nervous system and induces dysfunction in multiple organs/tissues, such as the gastrointestinal (GI) system. The neuroprotective effects of melatonin in SCI models have been reported; however, it is unclear whether the beneficial effects of melatonin are associated with alleviation of gut dysbiosis. In this study, we showed that daily intraperitoneal injection with melatonin following spinal cord contusion at thoracic level 10 in mice improved intestinal barrier integrity and GI motility, reduced expression levels of certain proinflammatory cytokines, improved animal weight gain and metabolic profiling, and promoted locomotor recovery. Analysis of gut microbiome revealed that melatonin treatment decreased the Shannon index and reshaped the composition of intestinal microbiota. Melatonin-treated SCI animals showed decreased relative abundance of Clostridiales and increased relative abundance of Lactobacillales and Lactobacillus, which correlated with alteration of cytokine (monocyte chemotactic protein 1) expression and GI barrier permeability, as well as with locomotor recovery. Experimental induction of gut dysbiosis in mice before SCI (i.e., by oral delivery of broad-spectrum antibiotics) exacerbates neurological impairment after SCI, and melatonin treatment improves locomotor performance and intestinal integrity in antibiotic-treated SCI mice. The results suggest that melatonin treatment restores SCI-induced alteration in gut microbiota composition, which may underlie the ameliorated GI function and behavioral manifestations.

It has been previously reported that the blockade of interleukin-7 receptor (IL-7R) promotes functional recovery following spinal cord injury (SCI), however, the direct function and molecular mechanism of IL-7 involved in this pathogenic process are unclear. Here, we report that, contrary to IL-7R blockade, the intraspinal administration of IL-7 limits functional recovery following SCI. In addition, IL-7 treatment promotes neuronal apoptosis in spinal cord lesions, which may be attributed to exacerbated focal inflammatory response, as shown by increased accumulation of activated microglia/macrophage and production of proinflammatory mediators. Moreover, IL-7 treatment activates JAK/STAT5 pathway following SCI. At last, more importantly, the pharmacological inhibition of STAT5 abrogates the effects of IL-7 treatment on functional recovery, neuronal apoptosis and focal inflammatory response, suggesting that the effects of IL-7 treatment following SCI are dependent on activating the JAK/STAT5 pathway. Overall, this study reveals the JAK/STAT5 pathway-dependent detrimental role of IL-7 following SCI, and also implies that targeting the IL-7/JAK/STAT5 axis may represent a potential therapeutic approach for SCI treatment.

Additional file 7: Table S2. Analysis of composition of microbiomes (ANCOM) between groups with values corrected for multiple comparisons using False Discovery Rate (FDR).

Additional file 6: Table S1. Fecal SCFAs contents in different groups.

Surgical decompression after spinal cord injury (SCI) is a conventional treatment. Although it has been proven to have clinical effects, there are certain limitations, such as the surgical conditions that must be met and the invasive nature of the treatment. Therefore, there is an urgent need to develop a simple and maneuverable therapy for the emergency treatment of patients with SCI before surgery. Rapamycin (RAPA) has been reported to have potential as a therapeutic agent for SCI. In this study, we observed the therapeutic effects of rapamycin and surgical decompression, in combination or separately, on the histopathology in rabbits with SCI. After combination therapy, intramedullary pressure (IMP) decreased significantly, autophagic flux increased, and apoptosis and demyelination were significantly reduced. Compared with RAPA/surgical decompression alone, the combination therapy had a significantly better effect. In addition, we evaluated the effects of mechanical pressure on autophagy after SCI by assessing changes in autophagic initiation, degradation, and flux. Increased IMP after SCI inhibited autophagic degradation and impaired autophagic flux. Decompression improved autophagic flux after SCI. Our findings provide novel evidence of a promising strategy for the treatment of SCI in the future. The combination therapy may effectively improve emergency treatment after SCI and promote the therapeutic effect of decompression. This study also contributes to a better understanding of the effects of mechanical pressure on autophagy after neurotrauma.

Surgical decompression after spinal cord injury (SCI) is a conventional treatment. Although it has been proven to have clinical effects, there are certain limitations, such as the surgical conditions that must be met and the invasive nature of the treatment. Therefore, there is an urgent need to develop a simple and maneuverable therapy for the emergency treatment of patients with SCI before surgery. Rapamycin (RAPA) has been reported to have potential as a therapeutic agent for SCI. In this study, we observed the therapeutic effects of rapamycin and surgical decompression, in combination or separately, on the histopathology in rabbits with SCI. After combination therapy, intramedullary pressure (IMP) decreased significantly, autophagic flux increased, and apoptosis and demyelination were significantly reduced. Compared with RAPA/surgical decompression alone, the combination therapy had a significantly better effect. In addition, we evaluated the effects of mechanical pressure on autophagy after SCI by assessing changes in autophagic initiation, degradation, and flux. Increased IMP after SCI inhibited autophagic degradation and impaired autophagic flux. Decompression improved autophagic flux after SCI. Our findings provide novel evidence of a promising strategy for the treatment of SCI in the future. The combination therapy may effectively improve emergency treatment after SCI and promote the therapeutic effect of decompression. This study also contributes to a better understanding of the effects of mechanical pressure on autophagy after neurotrauma.

Background Spinal cord injury (SCI) patients display disruption of gut microbiome, and gut dysbiosis exacerbate neurological impairment in SCI models. Cumulative data support an important role of gut microbiome in SCI. Here, we investigated the hypothesis that fecal microbiota transplantation (FMT) from healthy uninjured mice into SCI mice may exert a neuroprotective effect. Results FMT facilitated functional recovery, promoted neuronal axonal regeneration, improved animal weight gain and metabolic profiling, and enhanced intestinal barrier integrity and GI motility in SCI mice. High-throughput sequencing revealed that levels of phylum Firmicutes, family Christensenellaceae, and genus Butyricimonas were reduced in fecal samples of SCI mice, and FMT remarkably reshaped gut microbiome. Also, FMT-treated SCI mice showed increased amount of fecal short-chain fatty acids (SCFAs), which correlated with alteration of intestinal permeability and locomotor recovery. Furthermore, FMT downregulated IL-1β/NF-κB signaling in spinal cord and NF-κB signaling in gut following SCI. Conclusion Our study demonstrates that reprogramming of gut microbiota by FMT improves locomotor and GI functions in SCI mice, possibly through the anti-inflammatory functions of SCFAs.

Patients with spinal cord injury (SCI) have an increased risk for developing type 2 diabetes. It is unknown whether the pancreatic-islet microvascular vasomotion is involved. We used female C57BL/6 mice and a 100-kilodyne T10 Infinite Horizons contusion SCI (or T10 laminectomy) to detect blood glucose and pancreatic-islet microvascular vasomotion. Blood glucose obtained from tail vein was detected using one Touch UltraEasy glucometer. Glucose tolerance test was performed by d-glucose administration intraperitoneally. Functional status of pancreatic-islet microvascular vasomotion was determined by laser Doppler monitoring. Expressions of insulin and glucagon were determined by immunohistochemistry. Expression of VEGF-A was determined by immunohistochemistry and Western blotting. Our result demonstrated that blood glucose was significantly increased at 4 h postinjury compared to that in sham group, with continuous higher blood glucose until 4 days postinjury (p 0.05). SCI mice at day 7 and day 14 had significantly impaired glucose tolerance following glucose administration (p 0.01). Average blood perfusion, amplitude, frequency, and relative velocity of vasomotion were significantly lower at 6 h postinjury than those in the sham group (p 0.05), which were gradually upregulated over time. The expression of insulin was decreased, while the expression of glucagon was increased at 6 h postinjury. Similarly, the expression of VEGF-A was significantly decreased at 6 h postinjury, compared to that in sham group (p 0.05), with slight increases by 14 days postinjury. Our study suggests that the functional status of pancreatic-islet microvascular vasomotion is impaired after injury, which may have implications for developing effective therapeutic interventions for SCI.

Spinal cord injury (SCI) often leads to severe and permanent paralysis and places a heavy burden on individuals, families, and society. Until now, the therapy of SCI is still a big challenge for the researchers. Transplantation of mesenchymal stem cells (MSCs) is a hot spot for the treatment of SCI, but many problems and risks have not been resolved. Some studies have reported that the therapeutic effect of MSCs on SCI is related to the paracrine secretion of cells. The exosomes secreted by MSCs have therapeutic potential for many diseases. There are abundant pericytes which possess the characteristics of stem cells in the neurovascular unit. Due to the close relationship between pericytes and endothelial cells, the exosomes of pericytes can be taken up by endothelial cells more easily. There are fewer studies about the therapeutic potential of the exosomes derived from pericytes on SCI now. In this study, exosomes of pericytes were transplanted into the mice with SCI to study the restoration of motor function and explore the underlying mechanism. We found that the exosomes derived from pericytes could reduce pathological changes, improve the motor function, the blood flow and oxygen deficiency after SCI. In addition, the exosomes could improve the endothelial ability to regulate blood flow, protect the blood-spinal cord barrier, reduce edema, decrease the expression of HIF-1α, Bax, Aquaporin-4, and MMP2, increase the expression of Claudin-5, bcl-2 and inhibit apoptosis. The experiments in vitro proved that exosomes derived from pericytes could protect the barrier of spinal cord microvascular endothelial cells under hypoxia condition, which was related to PTEN/AKT pathway. In summary, our study showed that exosomes of pericytes had therapeutic prospects for SCI.

Neurogenic bowel dysfunction (NBD) and gut dysbiosis frequently occur in patients with traumatic cervical spinal cord injury (TCSCI). We evaluated neurogenic bowel management and changes in the gut microbiota in patients with TCSCI as well as associations between these changes and serum biomarkers. Fresh fecal and clinical data were collected from 20 male patients with TCSCI and 23 healthy males. Microbial diversity and composition were analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Moderate NBD was observed in patients with TCSCI. The diversity of the gut microbiota was lower in patients with TCSCI than in healthy adults. Furthermore, patients with TCSCI showed altered levels of serum biomarkers related to lipid metabolism, indicating unfavorable lipid profiles. Interestingly, Firmicutes had a positive effect and Verrucomicrobia had a negative effect on lipid metabolism (P < 0.05). At the genus level, Bacteroides and Blautia were significantly more abundant in patients than in healthy subjects and could be associated with lipid metabolism (P < 0.05). Faecalibacterium, Megamonas, and Prevotella, which were correlated with lipid metabolism markers, may be suitable targets for the treatment of TCSCI. Lactobacillus was positively correlated with glucose levels. The dysbiosis of several key gut bacteria was associated with serum biomarkers of lipid metabolism in patients with TCSCI. The observed interdependency of the microbiota and lipid metabolism provides a basis for understanding the mechanisms underlying lipid disorders after cervical SCI.

The aim of this study was to estimate the effect of melatonin on spinal cord perfusion, the permeability of blood-spinal cord barrier (BSCB), and edema at the contusion epicenter and regions rostral and caudal to the injury site in rats with spinal cord injury (SCI). Thirty-six female Sprague-Dawley rats were divided into three groups (12 animals in each group): sham, SCI, and melatonin groups. Melatonin (50 mg/kg) was injected intraperitoneally at 30 min after a moderate injury at T10 in the melatonin group (twice a day). At 24 h postinjury, spinal cord perfusion was estimated using laser Doppler flowmetry, the permeability of BSCB was detected by Evan's blue, and edema was estimated by calculating the water content. A linear regression analysis was performed to assess the correlation between spinal cord perfusion and the permeability of BSCB or water content. Our results showed that melatonin significantly upregulated spinal cord blood flow and oxygen saturation in SCI rats using laser Doppler perfusion monitoring. Simultaneously, laser Doppler perfusion imaging indicated that melatonin markedly meliorated spinal cord perfusion in regions rostral and caudal to the injury site, rather than the epicenter site. Consistent with the results of laser Doppler flowmetry, melatonin significantly reduced the amount of Evan's blue dye and water content in regions of rostral and caudal cords. In addition, perfusion correlated with the permeability of BSCB and water content. These findings indicated that melatonin might exert a protective effect by meliorating microcirculation, which coordinated a corresponding response in the integrity of BSCB and edema.

Melatonin can be neuroprotective in models of neurological injury, but its effects on blood vessel loss and neurological impairment following spinal cord injury (SCI) are unclear. Our goal herein was to evaluate the possible protective action of melatonin on the above SCI-induced damage in rats.Sixty-three female Sprague-Dawley rats were randomly divided into three equal groups: sham, SCI and melatonin groups. Melatonin (10 mg/kg) was injected intraperitoneally and further administered twice a day at indicated time after a moderate injury at T10 in melatonin group. Blood vessel was assessed by CD31staining and FITC-LEA, the permeability of blood-spinal cord barrier (BSCB) was detected by Evan's Blue. Neuron was assessed by NeuN staining and the expression of Nissl bodies in the neurons was assessed by Nissl staining. The expressions of brain-derived neurotrophic factor (BDNF), synapsin I, or growth associated protein-43 (GAP-43) in the spinal cord and hippocampus were evaluated by Western blotting.At 7 days post-injury, melatonin treatment rescued blood vessels, increased CD31 levels, ameliorated BSCB permeability. Additionally, melatonin significantly increased the number of neurons and the expression of Nissl bodies in neurons at the injury epicenter. Furthermore, our data showed that SCI reduced levels of the molecular substrates of neurological plasticity, including BDNF, synapsin I, or GAP-43 in the spinal cord and hippocampus. Melatonin treatment partially prevented these reductions.The neuroprotective effect of melatonin was associated with melioration of the microcirculation in the spinal cord and reduction of neurological impairment in the spinal cord and brain.

Background Neurogenic bowel dysfunction (NBD) is a major physical and psychological problem in patients with spinal cord injury (SCI), and gut dysbiosis is commonly occurs in SCI. Here, we document neurogenic bowel management of male patients with chronic traumatic complete SCI in our centre and perform comparative analysis of the gut microbiota between our patients and healthy males. Methods A total of 43 male patients with chronic traumatic complete SCI (20 with quadriplegia and 23 with paraplegia) and 23 healthy male adults were enrolled. Clinical data and fresh stool specimens were collected from all participants. Face-to-face interviews were conducted to survey the neurogenic bowel management of 43 patients with SCI. Gut microbiomes were analysed by sequencing of the V3–V4 region of the 16S rRNA gene. Results NBD was common in adult male patients with chronic traumatic complete SCI. Patients with quadriplegia exhibited a longer time to defecate than did those with paraplegia and had higher NBD scores and heavier neurogenic bowel symptoms. The diversity of the gut microbiota in the SCI group was reduced, and the structural composition was different from that of the healthy adult male group. The abundance of Veillonellaceae and Prevotellaceae increased, while Bacteroidaceae and Bacteroides decreased in the SCI group. The abundance of Bacteroidaceae and Bacteroides in the quadriplegia group and Acidaminococcaceae, Blautia, Porphyromonadaceae, and Lachnoclostridium in the paraplegia group were significantly higher than those in the healthy male group. Serum biomarkers (GLU, HDL, CR, and CRP), NBD defecation time and COURSE had significant correlations with microbial community structure. Microbial community structure was significantly associated with serum biomarkers (GLU, HDL, CR, and CRP), NBD defecation time, and COURSE. Conclusions This study presents a comprehensive landscape of the gut microbiota in adult male patients with chronic traumatic complete SCI and documents their neurogenic bowel management. Gut microbiota dysbiosis in SCI patients was correlated with serum biomarkers and NBD symptoms. Electronic supplementary material The online version of this article (10.1186/s12967-018-1735-9) contains supplementary material, which is available to authorized users.

Background Spinal cord injury (SCI) disturbs the autonomic nervous system and induces dysfunction or failure of multiple organs. The systemic microcirculation disturbance that contributes to the complications associated with SCI remains to be clarified. Methods We used male mice (29–32 g) and modified weight-drop injury at T10 to evaluate the systemic microcirculation dysfunction during the first 2 weeks after SCI. We determined permeability and microvascular blood flow in several organs and evaluated their vasomotor function. We also measured circulating endothelial cells (CECs), circulating endothelial progenitor cells (CEPCs), circulating pericyte progenitor cells (CPPCs), and serum proinflammatory cytokines. Results The endothelial permeability of almost all organs increased after SCI. Microvascular blood flow decreased in the bladder and kidney and increased in the spleen and was accompanied by endothelial vasomotor dysfunction. SCI also induced an increase in CECs, CEPCs, and CPPCs in peripheral blood. Finally, we confirmed changes in a systemic cytokine profile (interleukin [IL]-3, IL-6, IL-10, IL-13, granulocyte colony-stimulating factor, and regulated on activation normal T cell expressed and secreted) after SCI. Conclusions These data indicate that a systemic microcirculation disturbance occurs after SCI. This information may play a key role in the development of effective therapeutic strategies for SCI.

Laser Doppler flowmetry (LDF) is a noninvasive method for blood flow (BF) measurement, which makes it preferable for measuring microcirculatory alterations of the spinal cord. In this article, our goal was to use both Laser Doppler imaging and monitoring to analyze the change of BF after spinal cord injury. Both the laser Doppler image scanner and the probe/monitor were being employed to obtain each readout. The data of LDPI provided a local distribution of BF, which gave an overview of perfusion around the injury site and made it accessible for comparative analysis of BF among different locations. By intensely measuring the probing area over a period of time, a combined probe was used to simultaneously measure the BF and oxygen saturation of the spinal cord, showing overall spinal cord perfusion and oxygen supply. LDF itself has a few limitations, such as relative flux, sensitivity to movement, and biological zero signal. However, the technology has been applied in clinical and experimental study due to its simple setup and rapid measurement of BF.

Pericytes are contractile cells that wrap around the endothelial cells of capillaries throughout the body. They play an important role in regulating the blood brain barrier (BBB) and blood spinal cord barrier (BSCB). The differences between brain and spinal cord microvascular endothelial cells have been investigated. However, no report has elucidated the similarities and differences between brain microvascular pericytes (BMPs) and spinal cord microvascular pericytes (SCMPs) in vitro. The similarities were found between the two types of pericytes not only in the proliferation ability but also in the expression of toll like receptor 4. On the other hand, BMPs showed more than 2 fold in tubular length formation compared with SCMPs. The number of migratory SCMPs was larger than that of migratory BMPs. The expressions of connexin 43 and vascular endothelial growth factor (VEGF) in BMPs were increased compared with those in SCMPs, while SCMPs expressed more desmin and N-cadherin than BMPs. The abilities of tube-formation and migration between BMPs and SCMPs were markedly different, which might be mediated by VEGF, connexin 43, N-cadherin and desmin. These distinguishing features may reflect the more widespread differences between the BBB and BSCB which directly impact pathophysiological processes in various major diseases.

Spinal cord injury (SCI) can promote profound functional modification in various brain centers. However, the question of whether SCI can affect the generation of silent synapses that regulate neuronal plasticity in the hippocampus remains unclear. In the present studies, we demonstrated that acute SCI diminished silent synapses in hippocampus of lesioned rats. Furthermore, the SCI induced decline in silent synapses appeared to require the activation of NR2B-containing N-methyl-D-aspartate receptors. Our data show that SCI impaired synaptic plasticity in the hippocampus, suggesting that this region may serve as a potential therapeutic target for meliorating impaired brain functions after SCI.

The spinal cord microcirculation plays a critically important role in maintaining the normal function of spinal cord neurons, glial cells, and axons. Previous researches were largely focused on improved neurological manifestations of spinal cord injury (SCI) while ignoring to improve spinal cord microcirculation disorder after melatonin treatment. Therefore, the mechanism of melatonin that affects blood spinal cord barrier (BSCB) integrity and microcirculation in SCI remains unclear. The present study was performed to investigate the effect of melatonin on the BSCB in a SCI mice model. Melatonin (5, 10, 25, 50, 100 mg/kg i.p.) was administered to mice immediately following SCI. Compared to the 48 h post-SCI group, mice treated with melatonin (50 mg/kg) exhibited significantly reduced BSCB permeability. Additionally, melatonin treatment restrained microvessel loss; attenuated edema; protected the tight junction proteins, endothelial cells, and pericytes; decreased the number of cell apoptosis; and reduced MMP3/AQP4/HIF-1α/VEGF/VEGFR2 expression after SCI. Above all, our results clearly demonstrated that melatonin could stabilize microvascular barrier function and microcirculation of SCI, whose mechanism was to promote the repair of the damaged BSCB.