Intrathecal injection with dexmedetomidine maintained structure and function of blood-spinal cord barrier after ischemia reperfusion through down regulating FGFR3

English Keywords:Spinal cord ischemia reperfusion injury  Blood-spinal cord barrier  Fibroblast growth factor receptor 3  Occludin  Dexmedetomidine  Rat

English Abstract:

  【Abstract】 Objectives: To observe the effects of intrathecal injection with dexmedetomidine(Dex) on expressions of FGFR3, structure of blood-spinal cord barrier(BSCB), and related protein occludin after spinal cord ischemia reperfusion injury(SCIRI) in rat model. Methods: One hundred and twenty rats were randomly divided into four groups: sham group, IR group, Dex group and Dex+ATIP group. Intrathecal injection of 30μl normal saline was performed in sham group and IR group, 10μg dexmedetomidine(30μl) in Dex group, and 10μg dexmedetomidine and 10μg ATIP(total in 30μl) in Dex+ATIP group. Intrathecal injection was done once a day and continuously for 3 days. Aortic arch was only exposed but not occluded in sham group. SCIRI model in the other three groups were established by aortic arch occlusion for 14min. At 12h and 48h after model-making, L4-L6 segments of spinal cord were extracted. Spinal water content was determined by wet and dry method. Evan′s Blue(EB) extravasation was used to assess the structure of BSCB. Protein and mRNA expression of FGFR3 and occludin were assessed by Weston blot and PCR. Results: Compared with sham group, rats in IR group, Dex group and Dex+ATIP group had significantly higher spinal water content, EB extravasation, protein and mRNA levels of FGFR3, but lower protein and mRNA level of occludin at both 12h and 48h after model-making(P<0.05). Compared with IR group and Dex+ATIP group at the above time points, rats in Dex group had lower spinal water content, EB extravasation, protein and mRNA level of FGFR3, but higher level of occludin(P<0.05). There were no significant differences in the above indexes between IR group and Dex+ATIP group. At 12 and 48h after model-making, almost no red fluorescent stain was visualized in spinal cord parenchyma of sham group under microscopy, a little more fluorescent stain was observed in Dex group, but red fluorescent stain was observed markedly increase in IR group and Dex+ATIP group. The changes at 48h were more obviously than those at 12h. Conclusions: Intrathecal injection with Dex can maintain structure of BSCB and preserve expression of occludin by inhibiting spinal FGFR3 expression.