| BackgroundSpinal cord injury(SCI)is a severe central nervous system(CNS)disease,with traumatic spinal cord injury(TSCI)being the most common type.TSCI can lead to a series of serious complications,including pneumonia,atelectasis,respiratory failure,urinary tract infection,enteritis,pressure sore,sepsis,neurogenic shock,deep vein thrombosis,paralysis,sensory disorders,depression and anxiety,defecation disorders,sexual dysfunction,neuropathic pain,neurogenic bladder,autonomic reflex abnormalities,etc.Overall,approximately 16.2% of patients meet the diagnostic criteria for major depression disorder(MDD),but the prevalence of non-traumatic SCI is slightly higher than that of TSCI(21.1% vs.13.8%).It is estimated that approximately 30.66% of SCI patients are diagnosed with new or recurrent MDD(median time 74 days),and MDD is the most common complication(22.3%)in the first year after TSCI.MDD is closely related to immune disorders.The normal immune system of healthy individuals can not only resist the invasion of pathogenic microorganisms,but also constantly safeguard our mental health.Structurally,the hippocampal volume of MDD patients was significantly smaller than that of normal people.Histological studies have also confirmed that the number of hippocampal neurons in mice with depression like behavior secondary to TSCI is significantly reduced and microglia are activated.Numerous basic studies have shown that peripheral inflammation plays an important role in the evolution and progression of depression like behavior after SCI.SCI rats with depression like behavior contain higher levels of pro-inflammatory cytokines in the peripheral serum and also in the central nervous system.The activation of the peripheral and central immune systems can easily trigger depression,which has been proven in diseases involving autoimmune diseases and immune activation,such as multiple sclerosis and immune system activation during infections such as sepsis.It can be seen that trauma and inflammation have a significant impact on the evolution and progression of depressive behavior after SCI.ObjectiveDue to the inability to score the depression scale on experimental animals,this study is based on a novel depression classification method,aiming to preliminarily explore the relative levels of central and peripheral inflammation during the depression phase in rats identified by behavioral analysis as secondary depression like behavior of TSCI,as well as their potential connections with the evolution and progression of depression like behavior.MethodsFirstly,we constructed a rat contusion type SCI model using a domestically produced impactor.Subsequently,open field experiments,social exploration experiments,sugar water preference experiments,and forced swimming experiments were used to conduct behavioral evaluations on all rats at three time periods around the 10 th,20th,and 30 th days after injury.The results of the pre injury behavioral evaluation were used as baseline values to standardize the behavioral scores of the depression period around the 30 th day after injury,Finally,the rats with TSCI secondary depression like behavior and non-depression rats were comprehensively selected by hierarchical clustering method.During the process of completing all behavioral assessments,we evaluated and recorded the recovery of hind limb movement in each rat at a given time point based on the Basso-Beattie-Bresnahan(BBB)motor function scoring system.Secondly,we used fluorescence single labeling method to detect the apoptosis level,neuronal survival and microglia activation level near the CA1 area of hippocampus in each classification of rats.Finally,we used the ELISA kit method to detect and compare the relative levels of inflammatory factors in the peripheral serum of rats of different classifications.ResultsIn this study,we successfully constructed a rat contusion type SCI model.The BBB motor score showed that the overall motor function of the hind limbs of TSCI rats recovered to a certain extent within 35 days after injury.Based on hierarchical clustering method,8 of 29 TSCI rats(about 28%)were classified as depression group,and the remaining 21 TSCI rats were classified as non-depression group.In addition,all six sham group rats that underwent laminectomy were classified as non-depressed,and three non-depressed TSCI rats exhibited similar behavioral characteristics to sham group rats.Finally,compared with the TSCI rats identified as non-depressed by behavioral assessment,the TSCI rats with secondary depression like behavior had significantly higher apoptosis levels near the CA1 area of the hippocampus(P<0.001),neuron loss(P<0.001),large activation of microglia(P=0.001),and The levels of inflammatory factor TNFα(P < 0.001),IL-1 β(P=0.0431)and IL-6(P=0.0074)in the peripheral blood were significantly increased;Compared with Sham rats identified as non-depressed by behavioral assessment,non-depressed TSCI rats had significantly higher neuron loss(P<0.001)near hippocampal CA1 area(P<0.001),but microglia were not significantly activated,and only IL-1α(P=0.0279)was found in peripheral blood was significantly increased.ConclusionsTSCI rats exhibit continuous differentiation in behavioral performance,with approximately 28% of rats gradually achieving the worst depression related behavioral scores and being identified as depressed.At the histological level,the hippocampus neurons of rats with depression like behavior secondary to TSCI showed the most significant apoptosis and the lowest survival level of neurons.The inflammation levels in the hippocampus and peripheral blood of rats with TSCI secondary depressive behavior are higher than those of non-depressive rats,and inflammation may participate in and promotes the evolution and progression of depressive behavior in TSCI rats. |
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