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Diabetes mellitus (DM) is a common and chronic metabolic disease, which disturbs the internal environment, and then causes series of acute or chronic complications. Chronic hyperglycemia induces macroangiopathy and microangiopathy, which is synergistically regulated by intricate molecular mechanisms, including inflammatory responses, intracellular stress, pyrotosis and ferroptosis. DM hinders the repair of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) and aggravates the neurological damage. Pericytes are the main component of neurovascular units, which regulates angiogenesis, capillary blood flow, and BSCB permeability. After SCI, the BSCB is destroyed, the coverage rate of pericytes is significantly reduced. Then, it greatly affects the normal function of blood vessels. Diabetes not only plays a role in regulating the contraction phenotype and signal transduction of pericytes, but also changes the secretion genome spectrum of pericytes, and then affects the normal function of pericytes. Moreover, it has also been shown that diabetes promotes the loss of pericytes after SCI. This review systematically describes the regulatory effect of diabetes on pericytes in the vascular system, and the effect of diabetes mediated-pericyte injury on BSCB after SCI.
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Objective To investigate the mechanisms of basic fibroblast growth factor(bFGF) promoting blood spi-nal cord barrier(BSCB) recovery in rats after spinal cord injury(SCI).Methods Rats were randomly divided into sham group,SCI model group, bFGF intervention group(80 μg/kg). The nerve function of hind limb motor was evaluated by Basso, Beattie, and Bresnahan (BBB) scores during postoperative 14 days. Neuron loss of injured spinal cords was observed by haematoxylin and eosin(HE) staining and NeuN staining.The integrity of BSCB was investigated with Evan's Blue staining and fluorescein isothiocyanate (FITC)-dextran extravasation. The expression protein of adhesive connection protein (p120-catenin,β-catenin) and tight junction protein expression(occludin, claudin-5) were analyzed by Western blot.Results Compared with SCI model group, bFGF intervention group neuron loss decreased significantly at 3 d after injury(P<0.05);the permeability of blood spinal cord barrier obvi-ously reduced at 1d after injury; the expressions of p120-catenin, beta-catenin, occludin, claudin-5 protein of bFGF intervention group were increased dramatically at 1 d after injury(P<0.05). Conclusions bFGF improves the recovery of BSCB in an SCI model by reducing the loss of neurons and increasing the expressions of adhesion junction proteins and tight juction proteins.
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Aim To investigate the effect of sevoflurane preconditioning on spinal cord ischemia-reperfusion in-jury ( SCIRI ) of miR-199a-5p in rats. Methods Twenty-four SD rats were randomly divided into: group of sham ( Sham group) , group of ischemia-reperfusion ( I/R group ) , and group of sevoflurane and control ( SEVO+I/R group) . Sham group received the same operation, but did not inhale sevoflurane or close the aortic arch; SCIRI model was established after 14 min of the aortic arch of the non-invasive arterial clip in I/R group. SEVO+I/R group, before the establishment of SCIRI model, was inhaled 2.4% sevoflurane for 3 h. Basso Beattie Bresnahan scoring method was used to evaluate neuromotor function and TUNEL staining to observe apoptosis. Evans blue ( EB) was used to de-termine blood-spinal cord barrier ( BSCB) permeabili-ty; real-time qPCR to detect miR-199a-5p content;Western blot to measure the levels of caspase-9 and Bcl-2 in spinal cord tissues. Results Compared with sham group, the score of neuromotor function in I/R group decreased, cell apoptosis rate increased, BSCB permeability increased, miR-199a-5p expression de-creased, caspase-9 expression increased, and Bcl-2 expression decreased; compared with I/R group, the neurological motor function score of SEVO+I/R group increased, the apoptotic rate decreased, the BSCB per-meability decreased, the expression of miR-199a-5p increased, the expression of caspase-9 decreased, and the expression of Bcl-2 increased. Conclusion Sevoflurane pretreatment may reduce BSCB permeabili-ty and neuronal apoptosis by up-regulation of miR-199a-5p and protection of SCIRI in rats.
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Aim To investigate the effects of miR-122a on blood-spinal cord barrier after spinal cord ischemia-reperfusion injury in rats.Methods Thirty-six SD rats were randomly divided into three groups:group of sham(S group),group of control(C group)and group of miR-122a antagomir(M group).Rats in S group were subjected to exposure of aorta arch but without occlusion.Spinal ischemia-reperfusion injury was induced by clamping the aorta arch for 14 min in C group and M group.Rats in M group and C group were intrathecally injected with miR-122a antagomir or antagomir control daily for three times after injury.The miR-122a expression in injured spinal cord tissue was detected by real-time PCR.The occludin expression in injured spinal cord tissue was detected by Western blot.The permeability of blood-spinal cord barrier was examined using evans blue as a vascular tracer.The neurological motor function was evaluated by Basso Beattie Bresnahan score.Results Compared with S group,the expression of miR-122a was increased,the expression of occludin was decreased,the permeability of blood-spinal cord barrier was increased,and neurological motor function score was decreased significantly in C group(P<0.05).Compared with C group,the expression of miR-122a was decreased,the expression of occludin was increased,the permeability of blood-spinal cord barrier was decreased,and neurological motor function score was increased significantly in M group(P<0.05).Conclusion miR-122a can regulate the expression of occludin and change the permeability of blood-spinal cord barrier.
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Objective To investigate the effects of Propofol in blood spinal cord barrier (BSCB) disruption induced by spinal cord ischemia reperfusion injury (SCIRI). Methods 72 Japanese white rabbits were randomly assigned into 3 groups: sham-operation group (S); ischemia/reperfusion group (I/R) and Propofol treatment group (I/R + P). The Group S was separated the aorta without cross-clamping. SCIRI was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Propofol was intravenously infused at 10 minutes before aortic clamping and at onset of reperfusion in the Group I/R + P. The Group S and Group I/R were intravenously infused 0.9%sodium chloride. Hind-limb motor function was assessed using Tarlov criteria, and histological observation by histological examination. The permeability of the BSCB was examined using EB as vascular tracers. The expression of MMP-9, claudin-5 and NF-κB were assessed by Western blot, RT-PCR. Results Propofol minimized the neuromotor dysfunction and histopathological deficits and attenuated EB extravasation. In addition, Propofol suppressed SCIRI-induced increase of MMP-9 and NF-κB. Finally, Propofol reduced the loss of claudin-5. Conclusion Propofol stabilizes the BSCB integrity after SCIRI. This beneficial effect is partly mediated by inhibition of MMP-9 and preservation claudin-5 and relates to inhibiting the NF-κB signal pathway.
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@#Objective To investigate the influence of matrix metalloproteinases-9 (MMP-9) on permeability of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI). Methods 68 male C57BL/6 mice were randomly divided into sham group, 2 days group (S2), 7 days group (S7) and 14 days group (S14) after SCI with 17 mice in each group. All the groups received a moderate impacted spinal cord injury except the sham group. Evan's Blue (EB) was administered intraperitoneally to detect the permeability of BSCB. Occludin was analyzed by immunofluorescence, the expressions of occludin and MMP-9 were detected by Western blotting. Results After SCI, BMS score significantly reduced, compared with S2 group, S14 group showed a significant increase (P<0.01). The permeability of BSCB was seriously damaged after SCI. Compared with S2 group, S14 group showed a notable down-regulation in the permeability of injured micro-vessels (P<0.05). The expression of occludin was down-regulated and the expression of MMP-9 was up-regulated 7 days after SCI (P<0.05). Compared with S2 group, S14 group showed a significant up-regulation of occludin and a remarkable down-regulation of MMP-9 (P<0.05). Conclusion After SCI, MMP-9 might mediate the expression of occludin to influence the BSCB permeability.
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Objective To investigate the influence of matrix metalloproteinases-9 (MMP-9) on permeability of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI). Methods 68 male C57BL/6 mice were randomly divided into sham group, 2 days group (S2), 7 days group (S7) and 14 days group (S14) after SCI with 17 mice in each group. All the groups received a moderate impacted spinal cord injury ex-cept the sham group. Evan's Blue (EB) was administered intraperitoneally to detect the permeability of BSCB. Occludin was analyzed by im-munofluorescence, the expressions of occludin and MMP-9 were detected by Western blotting. Results After SCI, BMS score significantly reduced, compared with S2 group, S14 group showed a significant increase (P<0.01). The permeability of BSCB was seriously damaged af-ter SCI. Compared with S2 group, S14 group showed a notable down-regulation in the permeability of injured micro-vessels (P<0.05). The expression of occludin was down-regulated and the expression of MMP-9 was up-regulated 7 days after SCI (P<0.05). Compared with S2 group, S14 group showed a significant up-regulation of occludin and a remarkable down-regulation of MMP-9 (P<0.05). Conclusion After SCI, MMP-9 might mediate the expression of occludin to influence the BSCB permeability.
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Objective To examine the expression of tight junction protein claudin-5 in blood-spinal cord barrier (BSCB) after spinal cord injury about rat. Methods One hundred-twenty adult male SD rats were randomly divided into blank group (60) and injured group (60). The animal model of spinal cord injury was established using modified Allen method. The expression of claudin-5 in BSCB was examined at 6 h, 12 h, 1 d, 3 d, 5 d and 7 d (five rats per time point). Western blot and RT_PCR were used to detect protein and mRNA expression levels of claudin-5, respectively. Results The success rate of spinal cord injury molding was 81.7%. In injured group, EB content increased gradually over time, reached the peak at the third day(0.9435 ± 0.0813)μg/g and then reduced gradually (P<0.05), EB content was signifi-cantly higher in injured group than in blank group. Claudin-5 mRNA expression in injured group reduced gradually over time and reached the lowest point at the third day(2.871 ± 0.527)and then increased gradually(P<0.05). Claudin-5 mRNA expression was significantly lower in injured group than in blank group(P<0.05). Claudin-5 protein expression in injured group reduced gradually over time, reached the lowest at the third day(0.072 ±0.008)and then increased gradually (P<0.05). Claudin- 5 protein expression was significantly lower in injured group than in blank group(P<0.05). Con-clusions The alteration of claudin-5 expression after SCI may lead to the permeability of BSCB, which may in turn con-tribute to the secondary spinal cord injury.
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Objective To study the effects of methylprednisolone on the permeability of blood-spinal cord barrier (BSCB) and claudin-5 expression after spinal cord injury in rats. Methods The rat model of spinal cord injury was estab?lished using modified Allen method. SD rats were randomly divided into sham-operated group, spinal cord injury group and methylprednisolone pretreatment group. The permeability of BSCB and expression of claudin–5 were assessed at 12 h, 1, 3, 5, and 7 d after the onset of spinal cord injury (five animals per each time point). RT-PCR and Western blot were used to detect the expression of claudin-5. Results The success rate of the model was 84.0%. EB content was sig?nificantly higher in spinal cord injury group than in sham-operated group at each time point (F value 27.732,P was lower in spinal cord injury group than in sham operated group at each time point (Fvalue 18.108,P<0.05). The pro?tein expression of Claudin-5 was higher in methylprednisolone pretreatment group than spinal cord injury group at each time point (F value 20.247,P<0.05). Conclusions Methylprednisolone improves permeability of BSCB after spinal cord injury probably through enhancing claudin-5 expression in rats.