The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping th...The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. The damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24- hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplification, labeling, and hybridization were used to obtain the microRNA expression profiles of each group. Bioinformatics analysis confirmed tour differentially expressed microRNAs （miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p） and their common target genes （Tmem69 and Cxcll0）. Compared with the sham group, miR- 22-3p was continuously upregulated in all three ischemia groups but was highest in the group with 11o reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identified the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury.展开更多
Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis （ACD）. CXCR3 in the spinal cord also con- tribut...Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis （ACD）. CXCR3 in the spinal cord also con- tributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3-/- mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund＇s adjuvant-induced chronic inflammatory pain were reduced in Cxcr3-/- mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water （AEW）. Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Further- more, touch-elicited itch （alloknesis） after compound 48/80 or AEW treatment was suppressed in Cxcr3-/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3-/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.展开更多
基金supported by a Grant from the National Natural Science Foundation of China,No.81350013,31572217,and 81672263
文摘The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. The damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24- hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplification, labeling, and hybridization were used to obtain the microRNA expression profiles of each group. Bioinformatics analysis confirmed tour differentially expressed microRNAs （miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p） and their common target genes （Tmem69 and Cxcll0）. Compared with the sham group, miR- 22-3p was continuously upregulated in all three ischemia groups but was highest in the group with 11o reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identified the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury.
基金supported by Grants from the National Natural Science Foundation of China(31371121,81300954,and 31671091)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China
文摘Recent studies have shown that the chemokine receptor CXCR3 and its ligand CXCL10 in the dorsal root ganglion mediate itch in experimental allergic contact dermatitis （ACD）. CXCR3 in the spinal cord also con- tributes to the maintenance of neuropathic pain. However, whether spinal CXCR3 is involved in acute or chronic itch remains unclear. Here, we report that Cxcr3-/- mice showed normal scratching in acute itch models but reduced scratching in chronic itch models of dry skin and ACD. In contrast, both formalin-induced acute pain and complete Freund＇s adjuvant-induced chronic inflammatory pain were reduced in Cxcr3-/- mice. In addition, the expression of CXCR3 and CXCL10 was increased in the spinal cord in the dry skin model induced by acetone and diethyl ether followed by water （AEW）. Intrathecal injection of a CXCR3 antagonist alleviated AEW-induced itch. Further- more, touch-elicited itch （alloknesis） after compound 48/80 or AEW treatment was suppressed in Cxcr3-/- mice. Finally, AEW-induced astrocyte activation was inhibited in Cxcr3-/- mice. Taken together, these data suggest that spinal CXCR3 mediates chronic itch and alloknesis, and targeting CXCR3 may provide effective treatment for chronic pruritus.
