Exercise attenuates neurological deficits by stimulating a critical HSP70/NF-ΚB/IL-6/synapsin I axis in traumatic brain injury rats

Background: despite previous evidence for a potent inflammatory response after a traumatic brain injury (tbi),it is unknown whether exercise preconditioning (ep) improves outcomes after a tbi by modulating inflammatory responses. methods: we performed quantitative real-time pcr (qpcr) to quantify the genes encoding 84 cytokines and chemokines in the peripheral blood and used elisa to determine both the cerebral and blood levels of interleukin-6 (il-6). we also performed the chromatin immunoprecipitation (chip) assay to evaluate the extent of nuclear factor kappa-b (nf-κb) binding to the dna elements in the il-6 promoter regions. also,we adopted the western blotting assay to measure the cerebral levels of heat shock protein (hsp) 70,synapsin i,and β-actin. finally,we performed both histoimmunological and behavioral assessment to measure brain injury and neurological deficits,respectively. results: we first demonstrated that tbi upregulated nine pro-inflammatory and/or neurodegenerative messenger rnas (mrnas) in the peripheral blood such as cxcl10,il-18,il-16,cd-70,mif,ppbp,ltd,tnfrsf 11b,and faslg. in addition to causing neurological injuries,tbi also upregulated the following 14 anti-inflammatory and/or neuroregenerative mrnas in the peripheral blood such as ccl19,ccl3,cxcl19,il-10,il-22,il-6,bmp6,ccl22,il-7,bmp7,ccl2,ccl17,il-1rn,and gpi. second,we observed that ep inhibited both neurological injuries and six pro-inflammatory and/or neurodegenerative genes (cxcl10,il-18,il-16,cd70,mif,and faslg) but potentiated four anti-inflammatory and/or neuroregenerative genes (bmp6,il-10,il-22,and il-6). prior depletion of cerebral hsp70 with gene silence significantly reversed the beneficial effects of ep in reducing neurological injuries and altered gene profiles after a tbi. a positive pearson correlation exists between il-6 and hsp70 in the peripheral blood or in the cerebral levels. in addition,gene silence of cerebral hsp70 significantly reduced the overexpression of nf-κb,il-6,and synapsin i in the ipsilateral brain regions after an ep in rats. conclusions: tbi causes neurological deficits associated with stimulating several pro-inflammatory gene profiles but inhibiting several anti-inflammatory gene profiles of cytokines and chemokines. exercise protects against neurological injuries via stimulating an anti-inflammatory hsp70/nf-κb/il-6/synapsin i axis in the injured brains. © 2017 the author(s).