Corticostatin-6

Objective: To investigate the changes of gene expression in early stage of hemitransection of spinal cord and the regulatory effects of the traditional Chinese mixture Suifukang (SFK) on these changes. Methods: Eighty-six adult male SD rats were randomly divided into 3 groups: Suifukang group (Group S, n = 31, administered with SFK 3 days before the hemitransection at the dose of 2.5 g crude drugs/100 kg body weight QD and then 4 h and 8 h after hemitransection), model group (Group M, n = 45, administered with normal saline in the manner as in Group S), and normal control group (Group N, n = 10, without any treatment). The rats of Groups S and M underwent hemitransection of spinal cord at the level T12 three days before treatment. Twenty-four hours after the spinal cord injury (SCI), the rats were anesthetized and the injured tissues of Groups S and M and the corresponding tissues of Group N were removed. Total RNA was extracted, mRNA was purified and marked by Cy3 or Cy5 fluorescence labeling to synthesize cDNA hybridized probe that was hybridized with Biostars gene chip. Then the chip was scanned with ScanArray500 scanning apparatus. The data were analyzed by Imagene3.0 software. Results: There were 139 differentially expressed genes in Group M, 83 up-regulated and 56 down-regulated, involved in multifarious functions, such as cell metabolism, especially lipid metabolism, and regulation of ionic channel, immunity and defense, cytoskeleton protein, extracellular matrix, cell cycle, etc. There were 37 differentially expressed gene in Group S, 11 up-regulated, such as such Anxal, Ca(2+)-ATPase, IL-1 beta, Ofp, and 26 down-regulated, such as HSP-70 and Psap, several being key genes related to protection and regeneration of neuron. Conclusion: In the early stage after SCI many genes related to nervous degeneration, necrosis, traumatic inflammation, secondary injury of spinal cord, and aborted regeneration, etc, are expressed differentially. SFK regulates the changes of gene expression induced by SCI, thus initiating the protective effect of nervous tissues and promoting and supporting the regeneration of injured nervous tissues.

Objective: To investigate the characteristic changes of expression of the genes with specific functions in acute spinal cord injury (SCI). Methods: Nine SD rats were randomly divided into 3 equal groups: SCI 8-hour group in which modified Allen's falling strike method was used to establish spinal cord contusion model, the spinal cords were taken out 8 hours later to undergo examination of the gene expression profile by using cDNA microarray including 13 200 gene, 12 genes were selected to undergo semi-quantitative RT-PCR, and the up-regulation of the candidate gene C/EBPdelta was verified by in situ hybridization and immunohistochemistry.; SCI 72-hour group undergoing the same treatment, however, with the spinal cord taken out 72 hours later; and control group undergoing only sham operation with the spinal cord taken out immediately. Results: In the SCI 8 hour group the expression of 52 genes differed in comparison with the control group, 30 genes, including those related to transcription factors, oxidative stress, complement, pro-inflammatory reaction, and anti-inflammatory reaction, were up-regulated and 22 genes related to ion channel, synaptic proteins, and cytoskeletal proteins, were down-regulated. In the SCI 72-hour group the expression of 44 genes with known functions related to growth/differentiation/survival, axonal guidance, neuron regeneration, signal transduction, ubiquitin-proteasome system, and tumor suppressor differed, 26 genes were up-regulated and 18 down-regulated, in comparison with the control group. Semi-quantitative RT-PCR results of the 12 genes were consistent with those by the microarray examination. Conclusion: Significant changes occur in the early stage of SCI. Expressed at a high level in SCI, C/EBPdelta may be a therapeutic target of SCI.

Study design: Basic imaging experiment. Objective: To explore the use of 2-photon-excited fluorescence (2PEF) microscopy to investigate the therapeutic effect of methylprednisolone (MP) in mice with spinal cord injury (SCI). Summary of background data: MP can alleviate secondary SCI through its anti-inflammatory effect; however, how MP regulates axonal dynamics in a compression SCI model is not well characterized. We used 2PEF microscopy to trace axonal dynamics in vivo during MP therapy. Methods: Two types of transgenic mice (weighing 23-25 g) including YFP-H line (n = 18) and CX3CR1-GFP (n = 18) were used for experimental procedure. Each type of mouse was randomly divided into 3 groups, and the sample size of every subgroup was 6. The sham groups including YFP-H line group (n = 6) and CX3CR1-GFP group (n = 6) received laminectomy only (group 1). SCI groups received saline treatment (group 2) and SCI groups received MP treatment (group 3). Hind limb motor function was evaluated using the Basso Mouse Scale. 2PEF microscopy was used to image in vivo axonal dynamics at baseline and at 0.5 hours, 24 hours, 48 hours, and 72 hours postinjury. Histology was employed to examine pathological changes and microglial/macrophage proliferation after all imaging sessions. Results: Group 1 exhibited no significant differences in hind limb motor function before versus after surgery. The Basso Mouse Scale scores were significantly lower in groups 2 and 3 than in group 1 (P < 0.05). Degree of recovery was higher in group 3 than in group 2 at 7 days postinjury (P < 0.05). The axons in group 1 remained intact at all time points. The survival rate of axons in groups 2 and 3 progressively decreased at 48 hours postinjury; at 72 hours postinjury, the axon survival rate was higher in group 3 than group 2 (P < 0.05). Histology revealed that group 3 presented milder damage in injured spinal cord than group 2. Microglial/macrophage proliferation was lower in group 3 than in group 2 (P < 0.05). Conclusion: 2PEF microscopy is useful for detecting early changes, indicating axonal disruption in compression SCI. MP therapy may help alleviate axonal progressive damage and reduce the proliferation of microglia/macrophages in acute SCI. Level of evidence: N/A.