Carbamylated erythropoietin ameliorating hypothermia in rats with traumatic brain injury combined with seawater immersion
Objective To evaluate the effect of carbamylated erythropoietin(C-EPO)on hypothermia in rats with traumatic brain injury combined with seawater immersion(TBI-SIH),and its relationship with NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasomes.Methods A total of 36Sprague-Dawley(SD)rats were randomly divided into three groups:sham group(n=12),TBI+SIH group(n=12),and C-EPO treatment group(n=12).The controlled cortical impact(CCI)TBI injury method and constant temperature water bath immersion method were employed to establish a TBI+SIH rat model.C-EPO was administered at a dose of 50 μg/kg every 24 hours.Forty-eight hours after modeling,the modified neurological severity score(mNSS)and open field test were conducted.The ELISA was employed to test the levels of IL-1β,IL-18,and Caspase-1 within the injury region,while quantitative polymerase chain reaction(qPCR)was utilized to assess the expression levels of NLRP3 mRNA,caspase-1 mRNA,and IL-18 mRNA.Results Compared with the sham group,the TBI+SIH group exhibited increased mNSS values[(9.9±0.8)points],and decreased total movement distance[(26 743±2 034)mm]and stay time in central area[(7.7± 1.5)s]in the open field test,elevated brain water content[(82.16±3.25)％]and EB content[(33.49± 5.28)μg/g],and increased levels of IL-1β[(476.0±34.7)pg/mg],IL-18[(1 501.0±113.2)pg/mg],and caspase-1[(1 873.0±156.0)pg/mg]in the injury area,and significantly upregulated expressions of NLRP3 mRNA(1.48±0.19),Caspase-1 mRNA(1.90±0.49),and IL-18 mRNA(2.92±0.63)(P＜0.05).Compared with the TBI+SIH group,the C-EPO treatment group showed reduced mNSS scores[(5.2±0.7)points],increased total movement distance[(45 901±3 425)mm]and stay time in central area[(21.0±3.5)s]in the open field test,decreased brain water content[(80.79±3.40)％]and EB content[(19.23±3.76)μg/g],reduced levels of IL-1β[(412.0±22.0)pg/mg],IL-18[(660.0±45.8)pg/mg],and caspase-1[(1 123.0± 121.9)pg/mg]in the injured cortex,and downregulated expressions of NLRP3 mRNA(0.96±0.11),Caspase-1 mRNA(0.93±0.30),and IL-18 mRNA(1.28±0.35)(P＜0.05).Compared with the sham group,the TBI+SIH group showed obvious cerebral edema and cerebral hemorrhage;compared with the TBI+SIH group,the C-EPO treatment group had less cerebral edema,clearer brain structure,and the degree of cerebral hemorrhage was obviously milder.Conclusion C-EPO can reduce brain damage in TBI-SIH rats,and the mechanism of action may be related to inhibition of the activation of NLRP3 inflammasomes.
Traumatic brain injurySeawater immersion hypothermiaCarbamylated erythropoietinNLR familyThermal protein domain associated protein 3
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