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Objective@#To investigate the protective effect of propofol on neurological function in rats after traumatic brain injury (TBI) and its possible mechanism.@*Methods@#A total of 96 SD rats were randomly divided into sham operation group, sham operation+ propofol group, TBI group and TBI + propofol group, with 24 rats in each group. The TBI model was prepared by modified Feeney method. The sham operation+ propofol group and the TBI+ propofol group were given 50 mg/kg of propofol once daily. The sham operation group and the TBI group were injected with the same amount of normal saline. Modified neurobehavioral functional scores (mNSS) were evaluated at 1, 3, 7 and 14 days after injury; dry-wet specific gravity method was used to detect brain water content in injured area; TUNEL staining was used to detect neuronal apoptosis; chemiluminescence was used to detect activity of Oxygen cluster (ROS) content; Western blot was used to determine the expressions of inositol requirement enzyme 1 (IRE-1), enhancer binding protein homolog protein (CHOP), heme oxygenase 1 (HO-1), quinone oxidoreductase 1 (NQO1) and nuclear factor E2 related factor 2 (Nrf2) protein.@*Results@#Compared with the sham operation group and the sham operation + propofol group, the mNSS, brain tissue water content, apoptosis number and ROS increased at 1, 3, 7 and 14 days after TBI in the TBI group and TBI + propofol group (P<0.05). Compared with TBI group, mNSS in TBI+ propofol group decreased significantly [(9.3±1.4)points ∶(10.9±1.2)points] 7 days after injury (P<0.05); the brain tissue water content decreased significantly [(81.0±0.8)%∶(82.1±0.8)%] 3 days after injury (P<0.05); the number of apoptotic cells decreased significantly 7 days after injury[(14.1±1.4)%∶(15.6±1.6)%], with the most significant decrease at 14 days after injury [( 10.4±1.5)%∶(13.2±1.4)% (P<0.05); and ROS decreased significantly 7 days after injury [(61.5±4.0)RFU∶(77.3±5.5)RFU](P<0.05). Compared with the sham operation group and the sham operation+ propofol group, the expressions of IRE-1 and CHOP were significantly up-regulated in the TBI group and the TBI+ propofol group (P<0.05); the expressions of HO-1, NQO1 and Nrf2 in the TBI group were significantly decreased (P<0.05); the expressions of HO-1 and NQO1 in TBI+ propofol group were increased (P<0.05) while the expression of Nrf2 were decreased slightly (P<0.05). Compared with the TBI group, the expressions of IRE-1 and CHOP in TBI+ propofol group were decreased (P<0.05), while the expressions of HO-1, NQO1 and Nrf2 were significantly increased (P<0.05).@*Conclusion@#After TBI in rats, propofol can reduce oxidative stress by activating the Nrf2-antioxidant element (ARE) pathway, reduce brain edema, and inhibit neuronal apoptosis, thus playing a neuro-protective role.
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Objective To investigate the protective effect of propofol on neurological function in rats after traumatic brain injury (TBI) and its possible mechanism.Methods A total of 96 SD rats were randomly divided into sham operation group,sham operation + propofol group,TBI group and TBI +propofol group,with 24 rats in each group.The TBI model was prepared by modified Feeney method.The sham operation + propofol group and the TBI + propofol group were given 50 mg/kg of propofol once daily.The sham operation group and the TBI group were injected with the same amount of normal saline.Modified neurobehavioral functional scores (mNSS) were evaluated at 1,3,7 and 14 days after injury;dry-wet specific gravity method was used to detect brain water content in injured area;TUNEL staining was used to detect neuronal apoptosis;chemiluminescence was used to detect activity of Oxygen cluster (ROS) content;Western blot was used to determine the expressions of inositol requirement enzyme 1 (IRE-1),enhancer binding protein homolog protein (CHOP),heme oxygenase 1 (HO-1,quinone oxidoreductase 1 (NQO1) and nuclear factor E2 related factor 2 (Nrf2) protein.Results Compared with the sham operation group and the sham operation + propofol group,the mNSS,brain tissue water content,apoptosis number and ROS increased at 1,3,7 and 14 days after TBI in the TBI group and TBI + propofol group (P ＜ 0.05).Compared with TBI group,mNSS in TBI + propofol group decreased significantly [(9.3 ± 1.4) points ∶ (10.9 ± 1.2) points] 7 days after injury (P ＜ 0.05);the brain tissue water content decreased significantly [(81.0 ± 0.8) ％ ∶ (82.1 ± 0.8) ％] 3 days after injury (P ＜ 0.05);the number of apoptotic cells decreased significantly 7 days after injury [(14.1 ± 1.4) ％ ∶ (15.6 ± 1.6) ％],with the most significant decrease at 14 days after injury [(10.4 ± 1.5) ％ ∶ (13.2 ± 1.4) ％ (P ＜ 0.05);and ROS decreased significantly 7 days after injury [(61.5 ± 4.0) RFU∶ (77.3 ± 5.5) RFU] (P ＜ 0.05).Compared with the sham operation group and the sham operation + propofol group,the expressions of IRE-1 and CHOP were significantly up-regulated in the TBI group and the TBI + propofolgroup (P ＜ 0.05);the expressions of HO-1,NQO1 and Nrf2 in the TBI group were significantly decreased (P ＜0.05);the expressions of HO-1 and NQO1 in TBI + propofol group were increased (P ＜0.05) while the expression of Nrf2 were decreased slightly (P ＜ 0.05).Compared with the TBI group,the expressions of IRE-1 and CHOP in TBI + propofol group were decreased (P ＜ 0.05),while the expressions of HO-1,NQO1 and Nrf2 were significantly increased (P ＜ 0.05).Conclusion After TBI in rats,propofol can reduce oxidative stress by activating the Nrf2-antioxidant element (ARE) pathway,reduce brain edema,and inhibit neuronal apoptosis,thus playing a neuro-protective role.
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Objective To investigate the effects and mechanisms of glutamine (Gln) supplementation on oxidative stress,autophagy response and neurobehavioral outcome after traumatic brain injury (TBI) in rats.Methods TBI animal models were established using Feeney's method.Eighty SD rats were randomly divided into 4 groups:sham operation group (group Sham),Sham + glutamine supplementation group (group Sham+ GLN),traumatic brain injury group (group TBI),and TBI + glutamine supplementation group (group TBI+ GLN).We measured rat behavioral outcomes by modified neurologic severity score (mNSS) tests at day 1,3,7 and 14 after TBI.The apoptosis neurons in TBI cerebral cortex were determined by TUNEL staining.The expression of reactive oxygen species (ROS) was tested by ROS kits.Oxidative stress and autophagy related cytokines (HO-1,NQO1,Nrf2,LC3-Ⅱ and Beclin-1) were tested with Western blotting.Results Compared with the TBI group,the neurological function was improved [(9.79±0.43) vs.(8.43±0.30),F =6.775,P =0.010] and the apoptosis rate decreased (19.88％ ± 1.60％ vs.15.35％ ± 1.28％,P =0.013) in the TBI+ GLN group after 7-day treatment.Compared with the Sham group,the protein expression of ROS increased (P=0.000),and the expression of anti-oxidative stress factors (HO-1,NQO1) and Nrf2 pathway significantly decreased in the TBI group.After glutamine supplementation was given,the expression of ROS decreased and the expressions of HO-1 and NQO1 increased.The Nrf2 pathway and autophagy response also were activated with the expressions of Nrf2,LC3-Ⅱ and Beclin-1 increasing.Conclusion Glutamine supplementation can markedly reduce neuron apoptosis and improve neurological outcomes after TBI,thus has the protective effect on nerves by inhibiting TBI-induced oxidative stress response,activating Nrf2 pathway and autophagy response.
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Objective To investigate the effects of glutamine (Gln) supplementation on neurologica severity score,brain edema,neuron apoptosis,and endoplasmic reticulum stress (ERS) response after traumatic brain injury (TBI) in rats.Methods TBI rat models were established using modified Feeney's method.Eighty Sprague-Dawley rats were divided into 4 groups with a random number table:sham operation group (Sham group),TBI group,Gln supplementation group (TBI + Gln group) and ERS inducer 2-deoxy-D-glucose group (TBI +Gln + 2-DG group).We measured the rats' neurobehavioral outcomes by modified neurologic severity score (mNSS) on day 1,3,7 and 14 after TBI.Neuron apoptosis was detected using TUNEL staining.Brain water content was measured with wet-dry weight method.The apoptosis-related protein (caspase-12,caspase3,and Bcl-2) and ERS-related cytokines [inositol-requiring enzyme 1 (IRE-1),C/EBP homologous protein (CHOP)] expressions in TBI cerebral cortex were determined by immunohistochemistry staining and Western blot.Results Compared with the Sham group,the levels of brain edema,mNSS,apoptosis-related protein (caspase-12,caspase-3,Bcl-2) and ERS-related proteins (IRE-1,CHOP) were significantly increased in the other three groups (all P =0.00).Compared with the TB1 group,the TBI +Gln group showed significant lower brain water content [3 d:(81.39±0.59)％ vs.(83.54±0.52)％,P=0.04;7 d:(74.86±0.38)％ vs.(77.32±0.66)％,P=0.03],improved mNSS (8.63 ±0.22 vs.10.37±0.29,P=0.03),suppressed expressions of apoptosis-and ERS-related proteins (caspase-12,caspase-3,IRE-1,and CHOP)(P =0.01,P ＜ 0.01),and increased expression of anti-apoptotic protein Bcl-2 (P =0.02).Compared withthe TBI + Gln group,the expression of ERS-related factors (IRE-1 and CHOP),brain edema level,and neurological severity were increased in the TBI + Glu + 2-DG group.Conclusion Glutamine supplementation may have neuroprotection function,demonstrated as reducing brain edema and neuron apoptosis,and improving neurobehaviroal outcomes after TBI,possibly mediated by inhibiting TBI-induced ERS response.
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Objective To investigate the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) supplementation on neuron apoptosis,brain edema,activation of microglia,inflammatory response and neural function after traumatic brain injury (TBI) in rats,so as to understand the protection of ω-3 PUFA in rats following TBI and its mechanism.Methods TBI model was established using Feeney's method.Ninety SD rats were randomly divided into 5 groups:sham operation group (sham group),TBI group,TBI + selective activator of c-Jun N-terminal kinase (JNK) anisomycin group (TBI + Aniso group),TBI + ω-3 PUFA supplementation group (TBI + ω-3 group),and TBI + ω-3 PUFA supplementation + JNK activation group (TBI + ω-3 + Aniso group).We measured rat behavioral outcomes by modified neurological severity score (mNSS) on day 1,3,and 7 after TBI.Brain water content was measured with wet-dry weight method.The neuron apoptosis and microglial activation (identified by specific marker IBA-1) in TBI cerebral cortex were determined by TUNEL staining and immunofluorescence.Inflammatory cytokines [tumor necrosis factor-α (TNF-α),interleukin (IL)-1α,IL-1β,and IL-6] and the JNK signaling pathway (JNK,pJNK) were tested with reverse transcription-polymerase chain reaction and Western blot,respectively.Results Compared with the sham group,the levels of brain cell apoptosis,brain edema,neuron apoptosis,and inflammatory-relatived factors (TNF-α,IL-1 α,IL-1β,and IL-6) were significantly increased in the other four groups (P ＜ 0.05).Compared with the TBl group,ω-3 PUFA supplementation reduced brain water content following TBI,especially on day 3 after TBI [(78.14 ± 0.57) ％ vs.(82.31 ± 0.81) ％,P ＜ 0.01],and improved neurological function score (P ＜ 0.05).Meanwhile,ω-3 PUFA supplementation suppressed neuron apoptosis,the activation of microglia,and the mRNA and protein expressions of inflammatory cytokines (TNF-α,IL-1α,IL-1 β,IL-6).The activation of JNK signaling pathway was also inhibited by ω-3 PUFA.Conclusion ω-3 PUFA supplementation may markedly reduce brain edema,suppress neuron apoptosis,and improve neurological outcomes after TBI in rats,possibly mediated by inhibiting JNK signaling pathway and microglial activation,reducing microglia-induced cerebral inflammatory responses,demonstrated as down-regulated expression of TNF-α,IL-1α,IL-1β,and IL-6.
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As a transmembrane protein, β-amyloid precursor protein(β-APP) distributes extensively in the central nervous system, has the effect of neurotrophic, and neuroprotective, promote neurite growth and synaptogenesis, β-amyloid(Aβ) is the digestion products of its precursor-APP in the pathological conditions, and it is the main component of senile plaques-the main pathological changes of Alzheimer' s disease (AD), its toxic effects can also induce neuronal apoptosis, The expression of the two proteins after brain injuried has a close relationship with the injury, cognitive dysfunction, Alzheimer' s disease and the pathophysiological changes of central nervous system. To explore its expression in the brain after traumatic brain injury can determine the degree of injury, assess the prognosis and open up new avenues for the treatment of traumatic brain injury.