| Objective:1.To discover the changes of serum and cerebral spinal fluid periostin concentrations in rats with traumatic brain injury and further to verify whether periostin is derived from central nervous system.2.To discern the effects of intraventricular administration of periostin on neurologic function,brain edema,nervous cellular apoptosis and brain inflammation in rats with traumatic brain injury and further to demonstrate the role of periostin in traumatic brain injury.3.To elucidate the influence of intraventricular infection of periostin on cortical brain injury-related proteins(such as matrix metalloproteinase-9,zonulaoccludens-1,aquaporin-4,signal transducer and activator of transcription 3 and Janus kinase 2)expressions in traumatic brain injury rats and further to determine signalingmediating mechanisms of periostin for effects on traumatic brain injury.Methods:1.To set sham-operation group and traumatic brain injury group and then to analyze and compare the changes of serum and cerebral spinal fluid periostin concentrations after traumatic brain injury in rats and subsequently to ascertain periostin's origination from brain tissues.2.To form sham-operation group,traumatic brain injury and periostin intervention group and thereby to investigate effects of intraventricular administration of periostin on neurological function(modified neurological severity scores and escape latency in Morris water maze),brain edema,nervous cellular apoptosis(percentage of apoptotic nervous cells and expression of apoptosis-related FTAR9 protein),and brain inflammation(microglial specific protein OX-42 expression)in rats with traumatic brain injury and consequently to identify influence of periostin on traumatic brain injury.3.To configure sham-operation group,traumatic brain injury group and periostin intervention group and hence to inject periostin protein via intraventricular administration and thus to observe the effect of periostin on cortical brain injuryrelated proteins(i.e.,matrix metalloproteinase-9,zonulaoccludens-1,aquaporin-4,signal transducer and activator of transcription 3 and Janus kinase 2)expressions and to determine signaling-mediating mechanisms of periostin for effects on traumatic brain injury.Results: Part 1 Expression of periostin in rats with traumatic brain injury?1.HE staining for cerebral tissue in traumatic brain injury rats: no obvious bleeding occurred in rats in sham-operation group and there was an obvious bleeding in cerebral injured lesion for rats with traumatic brain injury.2.Change of periostin concentrations in the peripheral blood of rats with traumatic brain injury: As compared with periostin concentrations in the peripheral blood from rats in sham-operation group(84.1±10.9)ng/mL,periostin concentrations in the peripheral blood of rates in traumatic brain injury group were significantly elevated(164.3±19.3)ng/m L;and the difference was statistically significant(P < 0.05).3.Change of periostin concentrations in the cerebral spinal fluid of rats with traumatic brain injury: As compared with periostin concentrations in the cerebral spinal fluid from rats in sham-operation group(43.4±7.5)ng/mL,periostin concentrations in the cerebral spinal fluid of rates in traumatic brain injury group were significantly elevated(329.2±33.4)ng/mL;and the difference was statistically significant(P < 0.05).4.Comparison of periostin levels between cerebral spinal fluid and peripheral blood in rats with traumatic brain injury: Periostin levels were significantly higher in cerebral spinal fluid than in peripheral blood derived form rats in traumatic brain injury group(P < 0.05).Part 2 Effect of periostin on brain injury in rats with traumatic brain injury:1.HE staining for cerebral tissue in traumatic brain injury rats: no obvious bleeding occurred in rats in sham-operation group and there was an obvious and scattered bleeding in cerebral injured lesion for rats with traumatic brain injury and a marked and broad bleeding was found in cerebral injured lesion of rats in periostin intervention group.2.Effect of periostin on cognitive function of rats with traumatic brain injury: At days 6,7,8,9 and 10 after foundation of animal model,escape latencies of rats in sham-operation group were(67.0±6.9)s,(60.5±6.2)s,(53.2±4.8)s,(42.5±3.3)s and(34.0±3.4)s respectively;escape latencies of rats in traumatic brain injury group were(95.0±8.9)s,(88.8±11.7)s,(78.2±10.8)s,(71.3±10.5)s and(68.2±11.6)s respectively;and escape latencies of rats in periostin intervention group were(104.7±13.8)s,(99.5±13.5)s,(89.0±14.1)s,(86.0±12.5)s and(80.3±10.9)s respectively.As compared with rats in sham-operation group,escape latency was significantly prolonged(P<0.05);also,escape latency was significantly longer in rats from periostin intervention group than from traumatic brain injury group(P<0.05).3.Effect of periostin on modified neurological severity score in rats with traumatic brain injury: Rats in sham-operation group had a lowest score,namely 0.Rats in traumatic brain injury group had a mean score of(10.5±1.1)in modified neurological severity score.Rats in periostin intervention group had a mean score of(13.0±1.8)in modified neurological severity score.Modified neurological severity score was significantly higher among rats in traumatic brain injury group than in shamoperation group(P<0.05)and modified neurological severity score was significantly higher among rats in periostin intervention group than in traumatic brain injury group(P<0.05).4.Effect of periostin on nervous cellular apoptosis in rats with traumatic brain injury: Rats in sham-operation group had a mean apoptotic percentage of(6.8±0.7)%.Rats in traumatic brain injury group had a mean apoptotic percentage of(15.1±5.1)%.Rats in periostin intervention group had a mean apoptotic percentage of(28.0±4.3)%.Mean apoptotic percentage was significantly higher among rats in traumatic brain injury group than in sham-operation group(P < 0.05)and mean apoptotic percentage was significantly higher among rats in periostin intervention group than in traumatic brain injury group(P<0.05).5.Effect of periostin on cortical apoptosis-related protein TFAR19 expressions in rats with traumatic brain injury: Rats in sham-operation group had a mean relative TFAR19 expression percentage of(100.0±4.3)%.Rats in traumatic brain injury group had a mean relative TFAR19 expression percentage of(117.4±5.1)%.Rats in periostin intervention group had a mean relative TFAR19 expression percentage of(130.7±14.4)%.Mean relative TFAR19 expression percentage was significantly higher among rats in traumatic brain injury group than in sham-operation group(P<0.05)and mean relative TFAR19 expression percentage was significantly higher among rats in periostin intervention group than in traumatic brain injury group(P<0.05).6.Effect of periostin on brain water content in rats with traumatic brain injury: Rats in sham-operation group had a mean brain water content percentage of(78.3±1.5)%.Rats in traumatic brain injury group had a mean brain water content percentage of(80.0±1.1)%.Rats in periostin intervention group had a mean brain water content percentage of(81.9±1.3)%.Mean brain water content percentage was significantly higher among rats in traumatic brain injury group than in shamoperation group(P<0.05)and mean brain water content percentage was significantly higher among rats in periostin intervention group than in traumatic brain injury group(P<0.05).7.Effect of periostin on cortical microglial specific protein OX-42 expressions in rats with traumatic brain injury: Rats in sham-operation group had a mean relative OX-42 expression percentage of(100.0±21.7)%.Rats in traumatic brain injury group had a mean relative OX-42 expression percentage of(138.2±12.3)%.Rats in periostin intervention group had a mean relative OX-42 expression percentage of(168.8±31.2)%.Mean relative OX-42 expression percentage was significantly higher among rats in traumatic brain injury group than in sham-operation group(P<0.05)and mean relative OX-42 expression percentage was significantly higher among rats in periostin intervention group than in traumatic brain injury group(P<0.05).Part 3 Molecular mechanisms regarding effect of periostin on brain injury after traumatic brain injury:1.Influence of periostin on expressions of brain injury-related proteins in brain tissues of rats with traumatic brain injury: Among rats in sham-operation group,relative expression percentages of matrix metalloproteinase-9,zonulaoccludens-1 and aquaporin-4 in brain tissues were(100.0±14.3)%,(100.0±7.4)% and(100.0±8.4)% respectively;Among rats in traumatic brain injury group,relative expression percentages of matrix metalloproteinase-9,zonulaoccludens-1 and aquaporin-4 in brain tissues were(158.1±22.9)%,(51.7±18.6)% and(160.1±17.1)% respectively;Among rats in periostin intervention group,relative expression percentages of matrix metalloproteinase-9,zonulaoccludens-1 and aquaporin-4 in brain tissues were(204.4±24.4)%,(6.9±3.2)% and(230.1±34.3)% respectively.Relative expression percentages of matrix metalloproteinase-9 and aquaporin-4 were significantly higher among rats in traumatic brain injury group than in sham-operation group(both P<0.05)and relative expression percentages of matrix metalloproteinase-9 and aquaporin-4 were significantly higher among rats in periostin intervention group than in traumatic brain injury group(both P <0.05).Relative expression percentage of zonulaoccludens-1 was significantly lower among rats in traumatic brain injury group than in sham-operation group(P < 0.05)and relative expression percentage of zonulaoccludens-1 was significantly lower among rats in periostin intervention group than in traumatic brain injury group(P<0.05).2.Influence of periostin on signal transducer and activator of transcription 3 and Janus kinase 2 signaling pathway in brain tissues of rats with traumatic brain injury: Among rats in sham-operation group,relative expression percentages of signal transducer and activator of transcription 3 and Janus kinase 2 in brain tissues were(100.0±22.3)% and(100.0±14.6)% respectively;Among rats in traumatic brain injury group,relative expression percentages of signal transducer and activator of transcription 3 and Janus kinase 2 in brain tissues were(151.5±12.0)% and(130.4±12.8)% respectively;Among rats in periostin intervention group,relative expression percentages of signal transducer and activator of transcription 3 and Janus kinase 2 in brain tissues were(243.1±38.3)% and(173.7±10.1)% respectively.Relative expression percentages of signal transducer and activator of transcription 3 and Janus kinase 2 were significantly higher among rats in traumatic brain injury group than in sham-operation group(both P < 0.05)and relative expression percentages signal transducer and activator of transcription 3 and Janus kinase 2 were significantly higher among rats in periostin intervention group than in traumatic brain injury group(both P<0.05).Conclusions:1.Serum and cerebral spinal fluid periostin concentrations are significantly elevated in rats with traumatic brain injury and periostin levels are markedly higher in cerebral spinal fluid than in peripheral blood.2.Intraventricular administration of periostin aggravates neurological function defect of rats with traumatic brain injury,increases nervous cellular apoptosis,worsens cerebral edema,activates microglia,enhances expressions of matrix metalloproteinase-9,aquaporin-4,signal transducer and activator of transcription 3 and Janus kinase 2 as well as inhibits expression of zonulaoccludens-1.3.Those data indicate that,after traumatic brain injury in rats,expression of periostin protein is elevated;periostin possibly up-regulates signal transducer and activator of transcription 3 and Janus kinase 2 signaling pathway,regulates expressions of matrix metalloproteinase-9,zonulaoccludens-1 and aquaporin-4,damages blood-brain barrier,aggravates brain edema,activates brain inflammation,induces nervous cellular apoptosis and worsens neurologic function.Taken together,periostin might be implicated in pathophysiological processes underlying traumatic brain injury and inhibition of periostin expression could be a new approach for treatment of traumatic brain injury. |
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