Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characte...Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.展开更多
Fetuses and neonates are known to be high-risk groups for Methylmercury（MeHg）exposure.MeHg can be transferred to the fetus through the placenta and to newborn offspring through breast milk.The aim of the present stu...Fetuses and neonates are known to be high-risk groups for Methylmercury（MeHg）exposure.MeHg can be transferred to the fetus through the placenta and to newborn offspring through breast milk.The aim of the present study was to investigate the neurotoxic effects of low doses of MeHg（1 and 5 μg/m L in drinking water） administration,from gestational day 1 to postnatal day（PND） 21,on the neurobehavioral development of rats.The results showed that the no-observed-effect level of MeHg is somewhere in the range of 1-4 μg/mL.Neurobehavioral development analysis revealed a delayed appearance of cliff drop and negative geotaxis reflexes in the 5 μg/mL MeHg exposure group.Developmental exposure to MeHg affected locomotor activity functions for the females,but not for the males,implying that the female pups were more vulnerable than the male pups.All pups exposed to 5 μg/mL of MeHg showed a significant deficit in motor coordination in the rotarod test compared with controls,and the highest accumulated concentrations of Hg were found in the cerebellum,followed by the hippocampus and cerebral cortex,indicating that the cerebellum is a possible target for MeHg toxicity.We demonstrated adverse effects of developmental exposure to MeHg associated with tissue concentrations very close to the current human body burden of this persistent and bioaccumulative compound.展开更多
Objective:To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice.Methods:Swiss strain of albino female mice were divided into 6 groups of 5 animals...Objective:To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice.Methods:Swiss strain of albino female mice were divided into 6 groups of 5 animals in each:GroupⅠ(control group),groupⅡ(doxorubicin,10 mg/kg,i.v.),groupⅢ,Ⅳ,andⅤ(Nigella sativa oil;1.5,3,and 6 mL/kg,respectively),groupⅥ(Nigella sativa oil per se;6 mL/kg,p.o.).The duration of treatment was 15 d(10 days’pre-treatment and 5 days’post-treatment)and doxorubicin was administered on day 11th of the treatment schedule.Following Nigella sativa oil treatment,neurobehavioral tests,cardiac hypertrophy tests,and biochemical tests in serum and tissues were performed.Neurological tests included assessment of anxiety-like behavior in the elevated plus maze,spontaneous alternation behavior in the cross maze,and depression-like behavior in modified forced swim tests.Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB,malondialdehyde and reduced glutathione in tissues.Lastly,molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases.Results:Nigella sativa oil treatment significantly(P<0.001)restored doxorubicin-induced neurobehavioral changes,decreased lactate dehydrogenase and creatinine kinase-MB in the plasma,malondialdehyde contents in tissues,and increased reduced glutathione level.Besides,no significant alteration was observed in Nigella sativa oil per se group as compared to the control.Molecular docking showed that Nigella sativa oil components had appreciable binding affinitiy with the protein cavities of HDAC1 and HDAC6.Conclusions:The result shows that Nigella sativa oil exerts anxiolytic,antidepressant,and memory-enhancing effects in addition to cardioprotective effect against doxorubicin-induced cardiomyopathy in mice.The modulatory effect of Nigella sativa oil on oxidative stress could contribute to the cardioprotective effect and associated neurobehavioral changes in mice.展开更多
OBJECTIVE There is growing evidence that uridine may act as an endogenous neuromodulator with a potential signaling role in the central nervous system in addition to its function in pyrimidine metabolism.We previously...OBJECTIVE There is growing evidence that uridine may act as an endogenous neuromodulator with a potential signaling role in the central nervous system in addition to its function in pyrimidine metabolism.We previously found that acute morphine treatment significantly increased uridine release in the dorsal striatum of mice,while the mechanism involved in morphine-induced uridine release and the role of uridine in morphine-induced neurobehavioral changes have not been understood.METHODS Uridine release in the dorsal striatum of mice was assessed by in vivo microdialysis coupled with high performance liquid chromatography(HPLC) after morphine treatment.Western blotting and immunofluorescence were used to evaluate the expression of uridine-related proteins.Morphine-induced neurobehavioral changes were assessed by locomotor activity,behavioral sensitization and conditioned place preference(CPP)test.The expression of NT5E,an extracellular enzyme involved in formation of nucleosides,including uridine,was specifically knocked down in the dorsal striatum of mice using adeno-associated virus(AAV)-mediated short hairpin RNA(shRNA).RESULTS Both acute and chronic morphine administration significantly increased uridine release in the dorsal striatum,and this was associated with upregulation of NT5E but not other uridine-related proteins.Inhibition of NT5E with APCP or shRNA markedly inhibited morphine-induced uridine release in the dorsal striatum and related neurobehavioral changes,including hyperlocomotor activity,behavioral sensitization and CPP.CONCLUSION The present study increases our understanding of the contribution of NT5E in regulating morphine-induced neurobehavioral changes,at least as related to uridine,and suggests that NT5E may be a novel therapeutic target to manage morphine abuse.展开更多
Neurobehavioral and neurochemical effects of occupational lead exposure were invstigated by WHO Ncurobehavioral Core Test Battery (NCTB) testing and a serics of monoamine neurotransmitters and their metabolites analyz...Neurobehavioral and neurochemical effects of occupational lead exposure were invstigated by WHO Ncurobehavioral Core Test Battery (NCTB) testing and a serics of monoamine neurotransmitters and their metabolites analyzing in workers from lead smeltery and storage-battery manufacturing factory and matched controls. Indicators of lead exposure, the blood lead (PbB) and zinc protophorphyrin (ZPP) levels were found significantly higher in the expeed group compared with that of the controls (70.55μg/dL vs 3.6μg/dL; and 294.92 μg/dL vs 38.32μg/dL, respectively). Furthermore, elevated urinary homovanillic acid (HVA) and impairment of certain neurobehavioral performances were also found in the lead exposed wokers; the latter included attention/response speed, manual dexterity, perceptual-motor speed, visual perception/memory, and motor speed/steadiness. Positive or negative correlations were observed between certain parameters. Thus, homovanillic acid (HVA) is peitively correlated With PbB and ZPP; dopamine (DA) negatively correlated with Benton visual retention (BVR); and HVA negatively correlated with digit symbol (DSy), BVR, and pursuit aiming (PA). It is suggested that the alterations of dopamine and its metabolites HVA in urine associated with impairment of neurobehavioral function might be served as biomarkers of lead-induced neurotoxicity.展开更多
BACKGROUND： Recently, it has been reported that blood lead level lower than 24 μ mol/L can lead to learning and cognitive deficits. OBJECTIVE： To investigate the relationship of lead level in foremilk and early neu...BACKGROUND： Recently, it has been reported that blood lead level lower than 24 μ mol/L can lead to learning and cognitive deficits. OBJECTIVE： To investigate the relationship of lead level in foremilk and early neurobehavioral development of neonates taking lead level in foremilk as lead exposure index. DESIGN： A controlled observation. SETTING： Maternal and Child Health Center, Shanxi Children＇s Hospital. PARTICIPANTS： Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history. The corresponding puerperants were aged （27 ±5 ）years. They had no various acute and chronic diseases during pregnancy, and family history of neurological disease as well as occupational lead exposure. Informed consents of detected items were obtained from the puerperants. METHODS： ①Determination of lead level in foremilk- Altogether 128 foremilk samples, 1 mL each, were collected between January and February 2005. The same amount of violet acid was added to each sample. After foremilk was fully dissolved, 0.2 mL solution was taken for determining lead level with atomic absorption spectrometer in graphite stove. The determined process strictly followed the internal quantity control of laboratory and was involved in the blind quality control of Institute of Environmental Health of Chinese Academy. ②Participants grouping： Totally 128 neonates were involved, and the normal reference value of lead level of foremilk was 0.06 - 0.48 μ mol/L. The involved neonates were assigned into high-level lead group （≥ 0.24 μ mol/L, n =60） and low-level lead group （〈 0.24 μ mol/L, n =68）. ③Assessment of neurobehavioral development of neonates： Neurobehavioral development level of neonates who was born 24 to 72 hours was assessed with 20-item neonatal neurobehavioral determination method, which involved behavioral ability （6 items）, passive muscular tension （4 items）, active muscular tension （4 items）, primitive reflection （3 items） and general evaluation （3 items）. Each above-mentioned scoring had 3 scales （0,1 and 2 points）. The full mark of 20 items was 40 points. Neurological behaviors of neonates might be unabnormal when scoring was 〈 35 points. OUTCOME MEASURES： Assessment results of neurobehavioral development of neonates in high- and low-level lead neonates. RESULTS： After lead-level determination, the involved neonates in two groups participated in the final analysis. Neurobehavioral total scores of neonates of high-level lead group were lower than those in the low-level lead group [ （35.9±1.3 ） points vs. （37.7 ±1.4） points, P 〈 0.01 ]. The scores of neonatal erection in high-level lead group were lower than those in low-level lead group [ （ 1.4±0.4） points vs. （ 1.8 ±0.5 ） points, P 〈0.01], and time for head erection of neonates in the high-level lead group was shortened as compared with that in the low-level lead group [ （1.8±1.7） minutesvs. （3.3±2.2） minutes, P〈0.01]. CONCLUSION： 0.24 μ mol/L lead level in foremilk has certain relationship with neurobehavioral development. The main influenced manifestations are shortened duration of neonatal head erection and actively contracted extensor, i.e. cervical curved ability is weakened.展开更多
Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting a...Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important 'neurobehavioral' markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.展开更多
Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehaviora development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate fro...Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehaviora development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day （GD） 6 to postnatal day （PND） 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. Results No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. Conclusion Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.展开更多
Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be ...Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be blamed for these deficits.Exercise is widely recognized as promoting health and improving bad moods,but the mechanisms by which exercise affects SBI are still unclear.Methods:Lateral fluid percussion(LFP)method was used to fabricate moderate TBI in motor and somatosensory cortex of the C57 BL/6 J mice.A 4-weeks voluntary running wheel exercise with 6-day training per week was modified based on the previous protocols.Neurological status,sensorimotor function,spatial memory,electrophysiological,post-traumatic stress disorder(PTSD)associated anxiety and depression,cortical pathohistological changes were assessed to evaluate effects TBI and exercise intervention.Results:After moderate LFP injury,the TBI mice showed severe motor deficits at the early stage in acute phase but gradually recovered.During acute and subacute phase after TBI,novel object recognition(NOR)ability and spatial memory functions were consistently impaired in TBI mice;hippocampal firing frequency and burst probability were hampered.Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop.These electrophysiological impacts were associated with substantially lowered NOR preference as compared with the sham group during adulthood.4-weeks voluntary wheel running performed prior to induction of a moderate TBI,combined with 2 weeks voluntary motor skill training after TBI was found to inhibit plasma TNF-α,improve locomotor activity levels,alleviate anxiety and depression and promote spatial working memory recovery in rodents.At the meantime,histopathological deterioration was eased in the hippocampus in exercised mice.Conclusion:moderate TBI could induce neurological and neurobehavior impairments in mice.Aerobic exercise rehabilitation alleviated above mentioned deficits and may be an effective supplemental invention treatment for TBI patients.展开更多
Tetramethylammonium hydroxide(TMAH)is an important compound that utilized and released by the rapidly expanding semiconductor industry,which could hardly be removed by the conventional wastewater treatment techniques....Tetramethylammonium hydroxide(TMAH)is an important compound that utilized and released by the rapidly expanding semiconductor industry,which could hardly be removed by the conventional wastewater treatment techniques.As a cholinergic agonist,the tetramethylammonium ion(TMA^(+))has been reported to induce toxicity to muscular and respiratory systems of mammals and human,however the toxicity on aquatic biota remains poorly known.We investigated the neurotoxic effects of TMA^(+)exposure on zebrafish,based on neurobehavior tests and a series of biomarkers.Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L,and significant alterations on swimming path angles(straight and deflective movements)occurred even at 10 mg/L.The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species(ROS)and malondialdehyde(MDA),significantly negatively related with the activities of antioxidant enzymes,but not significantly correlated with the level of acetylcholinesterase(AChE).Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress,rather than the alterations of neurotransmitter.At the highest exposure concentration(200 mg/L),TMA^(+)evoked more severe toxicity on zebrafish juveniles,showing significantly stronger elevation on the MDA activity,and greater inhibitions on the activities of antioxidant enzymes and ACh E,suggesting juveniles were more susceptible to TMA^(+)exposure than larval zebrafish.展开更多
Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsis...Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsistent reports regarding its neurotoxicity.Here,we investigated thyroid disrupting effects and neurotoxicity of TBBPA(5,50,500μg/(kg·day))to male mice following maternal and direct exposure through drinking water,with the antithyroid drug propylthiouracil(PTU)as the positive control.On postnatal day(PND)15,we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups.The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum.During puberty and adulthood,the thyroid morphological alterations became more pronounced in the TBBPA-treated animals,accompanied by decreased serum thyroid hormone levels.Furthermore,the 50 and 500μg/(kg·day)TBBPA groups showed a significant decrease in the serum level of serotonin,a neurotransmitter associated with anxiety behaviors.Correspondingly,the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35,but this neurobehavioral alteration disappeared on PND 56.Moreover,no changes in neurobehavioral parameters tested were found in TBBPAtreated animals at puberty and adulthood.Altogether,all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice,suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.展开更多
OBJECTIVE:Electroacupuncture effect on neurological behavior and the expression of tyrosine kinase Janus kinase 2(JAK 2) of ischemic cortex in rats with the focal cerebral ischemia were investigated in this study.METH...OBJECTIVE:Electroacupuncture effect on neurological behavior and the expression of tyrosine kinase Janus kinase 2(JAK 2) of ischemic cortex in rats with the focal cerebral ischemia were investigated in this study.METHODS:The model of focal cerebral ischemia was established by the heat-coagulation induced the occlusion of the middle cerebral artery.The electro-acupuncture was applied on Baihui(GV 20) and Dazhui(GV 14),and AG490 was applied by intracerebroventricular infusion.The expressions of JAK2 mRNA and phospharylatedJAK2(p-JAK2) in the ischemic cortex were observed by in situ hybridization and western blotting.RESULTS:The expressions of JAK2 mRNA and p-JAK2 were rarely found in sham surgery group.In model group,the expression of JAK2 mRNA and JAK2 phosphorylation had increased.After 1 day of cerebral ischemia,the expression had reached its peak.After cerebral ischemia,the expressions of JAK2 mRNA and p-JAK2 were consistent with the neurological deficit score.Electroacupuncture treatment and AG490 intervention were able to improve the neurological deficit score after cerebral ischemia,and down-regulate the expressions of JAK2 mRNAand JAK2 phosphorylation.CONCLUSION:After cerebral ischemia,the excessive expressions of JAK2 and the JAK2 phosphorylation would be one of mechanisms by which the brain injury got worse.The therapy of electro-acupuncture could reduce the expression of JAK2,and inhibit JAK2 phosphorylated activation,so as to block the abnormal activation of signal transduction pathway which was induced by JAK2.展开更多
Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation ...Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.展开更多
BACKGROUND： Several studies have demonstrated that sustained cognitive tasks can induce cognitive fatigue and that the mean cerebral blood flow velocity changes in some cerebral regions during cerebral fatigue. OBJEC...BACKGROUND： Several studies have demonstrated that sustained cognitive tasks can induce cognitive fatigue and that the mean cerebral blood flow velocity changes in some cerebral regions during cerebral fatigue. OBJECTIVE： To dynamically monitor the changes in mean cerebral blood flow velocity in different brain regions of high performance fighter pilots during mental arithmetic tasks and consecutive performance tasks. DESIGN, TIME AND SETTING： The present neurophysiological trial, based on controlled observation, was performed at the Laboratory of Neurophysiology, Institute of Aviation Medicine, Air Force of China between January 2003 and December 2005. PARTICIPANTS： Forty-five males, high performance fighter pilots, averaging （27.6±2.5） years, were recruited for this study. METHODS： The mean cerebral blood flow velocity in the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery of subjects was dynamically tested using transcranial Doppler during 5- hour mental arithmetic tasks and during 5- hour consecutive performance tasks. The neurobehavioral ability index was analyzed throughout each trial according to the number of correct responses, false responses, and lost responses. Simultaneously, cerebral cognitive fatigue-induced lethargy was assessed by the Stanford Sleepiness Scale. MAIN OUTCOME MEASURES： Changes in mean cerebral blood flow velocity in the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery; neurobehavioral ability index of mental arithmetic and consecutive performance tasks; Stanford Sleepiness Scale scores. RESULTS： During mental arithmetic tasks, the mean cerebral blood flow velocity in the anterior cerebral artery increased during hour 2 and decreased after hour 4. There was no significant change in mean cerebral blood flow velocity in the middle cerebral artery and posterior cerebral artery. During hour 4, cerebral cognitive fatigue was observed and, simultaneously, Stanford Sleepiness Scale scores demonstrated the presence of fatigue. During such a stage, the neurobehavioral ability index decreased, indicating a decline in performance ability. During consecutive performance tasks, the mean cerebral blood flow velocity declined earlier in the posterior cerebral artery compared to the middle cerebral artery. CONCLUSION： Five- hour mental arithmetic tasks have few effects on cerebral functions and do not lead to a significant change in mean cerebral blood flow velocity. Five-hour consecutive performance tasks can induce cerebral cognitive fatigue, and a marked decline in mean cerebral blood flow velocity.展开更多
OBJECTIVES:To observe recovery in movement function in rats with middle cerebral artery occlusion(MCAO) after acupuncture treatment.METHODS:According to the randomized and controlled principle 1384 rats were divided i...OBJECTIVES:To observe recovery in movement function in rats with middle cerebral artery occlusion(MCAO) after acupuncture treatment.METHODS:According to the randomized and controlled principle 1384 rats were divided into the ba-sic control group(including the normal,sham,model control,model without intervention,Nimodipine,and para-Renzhong groups) and the acupuncture group(including the Neiguan(PC 6),Weizhong(BL 40),Sanyinjiao(SP 6),Chize(LU 5),Renzhong(GV 6) and non-acupoint groups).MCAO was modeled by Zea-longa's thread ligation and rats with scores of 1-3,as assessed by Zausinger's six-point method,were used in this study.Moreover,in the acupuncture group each acupoint was set with 12 different parameters by the orthogonal intersection method,resulting in 78 groups with 18 rats per group.The rats were treated by acupuncture once every 12 h for a total of six sessions and neurobehavioral scores were measured after each session.The neurobehavioral scores were compared by one-way ANOVA using the statistical software SPSS 17.0.RESULTS:After acupuncture therapy the mean neurobehavioral scores in MCAO rats increased gradually at each time point with a significant difference among the six scores,but with no significant differences between the fourth(48 h) and the fifth score(60 h),and between the fifth(60 h) and the sixth(72 h) score(P > 0.05).CONCLUSIONS:MCAO rats gradually recovered movement function over multiple acupuncture sessions.After the fouth acupuncture session(48 h),the neurobehavioral scores of rats with cerebral infarction remained stable.Acupuncture treatment had a reliable curative effect on movement function in cerebral infarction rats.展开更多
Abnormal postoperative neurobehavioral performance(APNP)is a common phenomenon in the early postoperative period.The disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a s...Abnormal postoperative neurobehavioral performance(APNP)is a common phenomenon in the early postoperative period.The disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a significant contribution to APNP.The dynamic changes of metabolites in different brain regions after anesthesia and surgery,as well as their potential association with APNP are still not well understood.Here,we used a battery of behavioral tests to assess the effects of laparotomy under isoflurane anesthesia in aged mice,and investigated the metabolites in 12 different sub-regions of the brain at different time points using proton nuclear magnetic resonance('H-NMR)spectroscopy.The abnormal neurobehavioral performance occurred at 6 h and/or 9 h,and recovered at 24 h after anesthesia/surgery.Compared with the control group,the altered metabolite of the model group at 6 h was aspartate(Asp),and the difference was mainly displayed in the cortex;while significant changes at 9 h occurred predominantly in the cortex and hippocampus,and the corresponding metabolites were Asp and glutamate(Glu).All changes returned to baseline at 24 h.The altered metabolic changes could have occurred as a result of the acute APNP,and the metabolites Asp and Glu in the cortex and hippocampus could provide preliminary evidence for understanding the APNP process.展开更多
BACKGROUND： Previously, only single short-time low-dose hyperbaric oxygenation （HBO） protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few...BACKGROUND： Previously, only single short-time low-dose hyperbaric oxygenation （HBO） protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few studies to report the outcome of administering long-time （can cover all the natural pathologic progression period） high-dose HBO to treat the disease. OBJECTIVE： To evaluate the therapeutic effect between two kinds of high-dose hyperbaric oxygenation on super-early stage of acute permanent middle cerebral artery occlusion （MCAO） in rats. DESIGN： A randomized controlled experimental study. SETTING： Beijing Tiantan Hospital, Capital Medical University; Beijing Research Institute of Neurosurgery. MATERIALS： Seventy-four male SD rats, aged 2.5 months old, weighing （ 280 ＋ 20） g, were provided by the Animal Institute, Chinese Academy of Medical Sciences. Hyperbaric oxygenation device was hyperbaric air cabin in which there was a self-made pure oxygen animal experimental cabin （made in China）. METHODS： This experiment was carried out in the municipal laboratory of Beijing Tiantan Hospital affiliated to Capital Medical University and Beijing Research Institute of Neurosurgery. ① Experimental intervention： All the rats were developed into models of permanent MCAO by suture embolism. Then, they were randomly divided into two HBO groups （9 hours and 18 hours） and control group, with 24 rats in each as well as 3-hour ultrastructure control group, with 2 rats. After being modeled for 3 hours, rats in the two HBO groups stayed in the hyperbaric cabin for 9 hours and 18 hours, separately. Rats in the 9-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7 and 9, and hyperbaric air at hours 2, 4, 6 and 8. Rats in the 18-hour HBO group inhaled pure oxygen at hours l, 3, 5, 7, 9, 11, 13, 15 and 17, and hyperbaric air at hours 2, 4, 6, 8, l0 12, 14, 16 and 18. After being created into models, rats in the control group and 3-hour ultrastructure control group breathed room air. ② Experimental evaluation： Neurologic functions of rat models in the 9-hour and 18-hour HBO groups as well as control group were scored by Bederson and Garica two neurological grading systems at hours 14 and 28 and on day 5; Infarct volume of rat models in the two HBO groups and control group was measured at hour 24 and on day 5 with NIH image processing software Image J; The pathological changes of brain tissue in the brain infarct region and its opposite region of rat models in the two HBO groups and 3-hour ultrastructure control group were observed with a Philips EM 208S transmission electron microscope. MAIN OUTCOME MEASURES： ① Neurobehavioral outcome. ② Rat brain infarct volume. ③ Ultrastructure of brain tissue in the ischemic penumbra of infarct models at the different time points RESULTS： ① Neurobehavioral outcome： After treatment, Garica score in the 9-hour and 18-hour HBO groups was significantly higher than that in the control group （P 〈 0.01）. Bederson score on day 5 after modeling in the 9-hour and 18-hour HBO groups was significantly lower than that in the control group （P 〈 0.01）. ② Cerebral infarct volume： Cerebral infarct volume in the 9-hour and 18-hour HBO groups was significantly smaller than that in the control group at hour 24 and on day 5 after modeling （P 〈 0.01）. In the 18-hour HBO group, infarct volume on day 5 after modeling was significantly larger than that at hour 24 after modeling （P 〈 0.05）. ③In the 3-hour ultrastructure control group, astrocyte edema and neuron damage around the capillary in the infarct cerebral tissue significantly relieved in the rats which were subjected to HBO. CONCLUSION： High dose of HBO is highly efficient in reducing infarct volume and improving neurobehavioral outcome of rats with acute cerebral infarction, and also has an important role in inhibiting the pathological progression of ischemic brain tissue after cerebral infarction.展开更多
A cross sectional epidemiological study of 93 arc welders in a shipyard was conducted to observe the adverse effect of exposure to manganese welding fumes. Among them, 37 workers with paired controls were given the ne...A cross sectional epidemiological study of 93 arc welders in a shipyard was conducted to observe the adverse effect of exposure to manganese welding fumes. Among them, 37 workers with paired controls were given the neurobehavioral tests. Air concentration of manganese in working place, hair manganese and platelet 5 hydroxytryptamine in both exposed workers and controls was also measured. The higher percentage of respiratory symptoms including sour throat and dyspnea in the welders were observed as compared with the controls. The results of neurobehavioral tests showed that the welders exhibited poorer performance in simple reaction time and Santa Ana dexterity tests than that in the controls. The hair manganese concentration was higher and the blood platelet 5 HT level decreased in the welders. In conclusion, symptoms in the welders might be related to the exposure of manganese. Long term exposure to manganese welding fume could cause the change in simple reaction time and Santa Ana dexterity tests. The hair manganese concentration could be used as a biological monitoring index of exposure to manganese.展开更多
Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of P...Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson＇s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson＇s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson＇s disease by modulating neurotransmitter signaling in the corpus striatum.展开更多
Length and thickness of 152 corpus callosa Using ultrasonic diagnostic equipment with a were measured in neonates within 24 hours ot b^rtn. neonatal brain-specific probe, corpus callosum length and thickness of the ge...Length and thickness of 152 corpus callosa Using ultrasonic diagnostic equipment with a were measured in neonates within 24 hours ot b^rtn. neonatal brain-specific probe, corpus callosum length and thickness of the genu, body, and splenium were measured on the standard mid-sagittal plane, and the anteroposterior diameter of the genu was measured in the coronal plane. Results showed that corpus callosum length as well as thickness of the genu and splenium increased with gesta- tional age and birth weight, while other measures did not. These three factors on the standard mid-sagittal plane are therefore likely to be suitable for real-time evaluation of corpus callosum de- velopment in premature infants using cranial ultrasound. Further analysis revealed that thickness of the body and splenium and the anteroposterior diameter of the genu were greater in male infants than in female infants, suggesting that there are sex differences in corpus callosum size during the neonatal period. A second set of measurements were taken from 40 premature infants whose ges- tational age was 34 weeks or less. Corpus callosum measurements were corrected to a gestational age of 40 weeks, and infants were grouped for analysis depending on the outcome of a neonatal behavioral neurological assessment. Compared with infants with a normal neurological assessment, corpus callosum length and genu and splenium thicknesses were less in those with abnormalities, indicating that corpus callosum growth in premature infants is associated with neurobehavioral development during the early extrauterine stage.展开更多
基金The authors extend their appreciation to the Distinguished Scientist Fellowship program at King Saud University,Riyadh,Saudi Arabia,for funding this work through Research Supporting Project Number RSP2024R131.
文摘Background:Besides seizures,a myriad of overlapping neuropsychiatric and cognitive comorbidities occur in patients with epilepsy,which further debilitates their quality of life.This study provides an in-depth characterization of the impact of brivaracetam and rufinamide individually and in combination at 10 and 20 mg/kg doses,respec-tively,on corneal kindling-induced generalized seizures and behavioral alterations.Furthermore,observed convulsive frequency and behavioral changes were corre-lated to post-kindling-induced changes in the activity of markers of oxidative stress.Methods:Adult C57BL/6 mice were kindled via twice-daily transcorneal 50-Hz elec-trical stimulations(3 mA)for 3 s for 12 days until animals reached a fully kindled state.After the kindling procedure,animals were tested using a set of behavioral tests,and neurochemical alterations were assessed.Results:Corneal-kindled animals exhibited intense generalized convulsions,altered behavioral phenotypes typified by positive symptoms(hyperlocomotion),negative symptoms(anxiety and anhedonia),and deficits in semantic and working memory.BRV 10+RFM 20 dual regime increased convulsive threshold and propensity toward the start of stage 4–5 seizures and improved phenotypical deficits,that is,anxiety,depression,and memory impairments.Moreover,this combination therapy mitigated kindling-induced redox impairments as evidenced by reduced malondialdehyde and acetylcholinesterase levels and increased glutathione antioxidant activity in the brain of animals subjected to repetitive brain insult.Conclusion:Based on our outcomes,this dual therapy provides supporting evidence in alleviating epilepsy-induced neurobehavioral comorbidities and changes in redox homeostasis.
基金financially supported by the National Natural Science Foundation of China (No.21177087)the National Program on Key Basic Research Project of China (973 Program) (No.2013CB430005)
文摘Fetuses and neonates are known to be high-risk groups for Methylmercury（MeHg）exposure.MeHg can be transferred to the fetus through the placenta and to newborn offspring through breast milk.The aim of the present study was to investigate the neurotoxic effects of low doses of MeHg（1 and 5 μg/m L in drinking water） administration,from gestational day 1 to postnatal day（PND） 21,on the neurobehavioral development of rats.The results showed that the no-observed-effect level of MeHg is somewhere in the range of 1-4 μg/mL.Neurobehavioral development analysis revealed a delayed appearance of cliff drop and negative geotaxis reflexes in the 5 μg/mL MeHg exposure group.Developmental exposure to MeHg affected locomotor activity functions for the females,but not for the males,implying that the female pups were more vulnerable than the male pups.All pups exposed to 5 μg/mL of MeHg showed a significant deficit in motor coordination in the rotarod test compared with controls,and the highest accumulated concentrations of Hg were found in the cerebellum,followed by the hippocampus and cerebral cortex,indicating that the cerebellum is a possible target for MeHg toxicity.We demonstrated adverse effects of developmental exposure to MeHg associated with tissue concentrations very close to the current human body burden of this persistent and bioaccumulative compound.
文摘Objective:To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice.Methods:Swiss strain of albino female mice were divided into 6 groups of 5 animals in each:GroupⅠ(control group),groupⅡ(doxorubicin,10 mg/kg,i.v.),groupⅢ,Ⅳ,andⅤ(Nigella sativa oil;1.5,3,and 6 mL/kg,respectively),groupⅥ(Nigella sativa oil per se;6 mL/kg,p.o.).The duration of treatment was 15 d(10 days’pre-treatment and 5 days’post-treatment)and doxorubicin was administered on day 11th of the treatment schedule.Following Nigella sativa oil treatment,neurobehavioral tests,cardiac hypertrophy tests,and biochemical tests in serum and tissues were performed.Neurological tests included assessment of anxiety-like behavior in the elevated plus maze,spontaneous alternation behavior in the cross maze,and depression-like behavior in modified forced swim tests.Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB,malondialdehyde and reduced glutathione in tissues.Lastly,molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases.Results:Nigella sativa oil treatment significantly(P<0.001)restored doxorubicin-induced neurobehavioral changes,decreased lactate dehydrogenase and creatinine kinase-MB in the plasma,malondialdehyde contents in tissues,and increased reduced glutathione level.Besides,no significant alteration was observed in Nigella sativa oil per se group as compared to the control.Molecular docking showed that Nigella sativa oil components had appreciable binding affinitiy with the protein cavities of HDAC1 and HDAC6.Conclusions:The result shows that Nigella sativa oil exerts anxiolytic,antidepressant,and memory-enhancing effects in addition to cardioprotective effect against doxorubicin-induced cardiomyopathy in mice.The modulatory effect of Nigella sativa oil on oxidative stress could contribute to the cardioprotective effect and associated neurobehavioral changes in mice.
基金National Natural Science Foundation of China(81373383).
文摘OBJECTIVE There is growing evidence that uridine may act as an endogenous neuromodulator with a potential signaling role in the central nervous system in addition to its function in pyrimidine metabolism.We previously found that acute morphine treatment significantly increased uridine release in the dorsal striatum of mice,while the mechanism involved in morphine-induced uridine release and the role of uridine in morphine-induced neurobehavioral changes have not been understood.METHODS Uridine release in the dorsal striatum of mice was assessed by in vivo microdialysis coupled with high performance liquid chromatography(HPLC) after morphine treatment.Western blotting and immunofluorescence were used to evaluate the expression of uridine-related proteins.Morphine-induced neurobehavioral changes were assessed by locomotor activity,behavioral sensitization and conditioned place preference(CPP)test.The expression of NT5E,an extracellular enzyme involved in formation of nucleosides,including uridine,was specifically knocked down in the dorsal striatum of mice using adeno-associated virus(AAV)-mediated short hairpin RNA(shRNA).RESULTS Both acute and chronic morphine administration significantly increased uridine release in the dorsal striatum,and this was associated with upregulation of NT5E but not other uridine-related proteins.Inhibition of NT5E with APCP or shRNA markedly inhibited morphine-induced uridine release in the dorsal striatum and related neurobehavioral changes,including hyperlocomotor activity,behavioral sensitization and CPP.CONCLUSION The present study increases our understanding of the contribution of NT5E in regulating morphine-induced neurobehavioral changes,at least as related to uridine,and suggests that NT5E may be a novel therapeutic target to manage morphine abuse.
文摘Neurobehavioral and neurochemical effects of occupational lead exposure were invstigated by WHO Ncurobehavioral Core Test Battery (NCTB) testing and a serics of monoamine neurotransmitters and their metabolites analyzing in workers from lead smeltery and storage-battery manufacturing factory and matched controls. Indicators of lead exposure, the blood lead (PbB) and zinc protophorphyrin (ZPP) levels were found significantly higher in the expeed group compared with that of the controls (70.55μg/dL vs 3.6μg/dL; and 294.92 μg/dL vs 38.32μg/dL, respectively). Furthermore, elevated urinary homovanillic acid (HVA) and impairment of certain neurobehavioral performances were also found in the lead exposed wokers; the latter included attention/response speed, manual dexterity, perceptual-motor speed, visual perception/memory, and motor speed/steadiness. Positive or negative correlations were observed between certain parameters. Thus, homovanillic acid (HVA) is peitively correlated With PbB and ZPP; dopamine (DA) negatively correlated with Benton visual retention (BVR); and HVA negatively correlated with digit symbol (DSy), BVR, and pursuit aiming (PA). It is suggested that the alterations of dopamine and its metabolites HVA in urine associated with impairment of neurobehavioral function might be served as biomarkers of lead-induced neurotoxicity.
基金Key Technologies Research and Development Program of Shanxi Province, No. 041074
文摘BACKGROUND： Recently, it has been reported that blood lead level lower than 24 μ mol/L can lead to learning and cognitive deficits. OBJECTIVE： To investigate the relationship of lead level in foremilk and early neurobehavioral development of neonates taking lead level in foremilk as lead exposure index. DESIGN： A controlled observation. SETTING： Maternal and Child Health Center, Shanxi Children＇s Hospital. PARTICIPANTS： Totally 128 neonates of full-term normal delivery, 76 male and 52 female, from Shanxi Provincial Maternal and Child Health Center and Jiexiu Maternal and Child Health Center were involved in this study. All the involved neonates had no peripartal ischemic/hypoxic history. The corresponding puerperants were aged （27 ±5 ）years. They had no various acute and chronic diseases during pregnancy, and family history of neurological disease as well as occupational lead exposure. Informed consents of detected items were obtained from the puerperants. METHODS： ①Determination of lead level in foremilk- Altogether 128 foremilk samples, 1 mL each, were collected between January and February 2005. The same amount of violet acid was added to each sample. After foremilk was fully dissolved, 0.2 mL solution was taken for determining lead level with atomic absorption spectrometer in graphite stove. The determined process strictly followed the internal quantity control of laboratory and was involved in the blind quality control of Institute of Environmental Health of Chinese Academy. ②Participants grouping： Totally 128 neonates were involved, and the normal reference value of lead level of foremilk was 0.06 - 0.48 μ mol/L. The involved neonates were assigned into high-level lead group （≥ 0.24 μ mol/L, n =60） and low-level lead group （〈 0.24 μ mol/L, n =68）. ③Assessment of neurobehavioral development of neonates： Neurobehavioral development level of neonates who was born 24 to 72 hours was assessed with 20-item neonatal neurobehavioral determination method, which involved behavioral ability （6 items）, passive muscular tension （4 items）, active muscular tension （4 items）, primitive reflection （3 items） and general evaluation （3 items）. Each above-mentioned scoring had 3 scales （0,1 and 2 points）. The full mark of 20 items was 40 points. Neurological behaviors of neonates might be unabnormal when scoring was 〈 35 points. OUTCOME MEASURES： Assessment results of neurobehavioral development of neonates in high- and low-level lead neonates. RESULTS： After lead-level determination, the involved neonates in two groups participated in the final analysis. Neurobehavioral total scores of neonates of high-level lead group were lower than those in the low-level lead group [ （35.9±1.3 ） points vs. （37.7 ±1.4） points, P 〈 0.01 ]. The scores of neonatal erection in high-level lead group were lower than those in low-level lead group [ （ 1.4±0.4） points vs. （ 1.8 ±0.5 ） points, P 〈0.01], and time for head erection of neonates in the high-level lead group was shortened as compared with that in the low-level lead group [ （1.8±1.7） minutesvs. （3.3±2.2） minutes, P〈0.01]. CONCLUSION： 0.24 μ mol/L lead level in foremilk has certain relationship with neurobehavioral development. The main influenced manifestations are shortened duration of neonatal head erection and actively contracted extensor, i.e. cervical curved ability is weakened.
文摘Because of the importance of central nervous system (CNS) functions to productive capacity and quality of life, biomarkers of these functions will play a key role in evaluating the success of interventions targeting aging processes. The CNS biomarkers may also be useful for predicting aging in other systems and in the organism as a whole. Age-related behavioral changes, the products of CNS aging, have content and predictive validity with respect to human functional capacities and may, therefore, represent important 'neurobehavioral' markers of functional aging. This article presents a discussion of some behavioral paradigms which are currently being considered as neurobehavioral biomarkers of aging in mice and the experimental approaches being employed in the assessment of their validity. Studies conducted in the authors' laboratory using dietary restriction and genetic comparisons to evaluate the validity of neurobehavioral biomarkers have revealed several methodological concerns, and hypothetical and empirical examples of these pitfalls are described and discussed. In spite of those concerns, it is concluded that approaches to validity using genetic comparisons and dietary restriction can be successfully implemented and should ultimately lead to identification of valid and useful neurobehavioral biomarkers of aging.
基金financially supported by the National Science and Technology Support Program(2012BAK01B00)
文摘Objective The aim of this study was to assess the effects of yttrium nitrate on neurobehaviora development in Sprague-Dawley rats. Methods Dams were orally exposed to 0, 5, 15, or 45 mg/kg daily of yttrium nitrate from gestation day （GD） 6 to postnatal day （PND） 21. Body weight and food consumption were monitored weekly. Neurobehavior was assessed by developmental landmarks and reflexes, motor activity, hot plate, Rota-rod and cognitive tests. Additionally, brain weights were measured on PND 21 and 70. Results No significant difference was noted among all groups for maternal body weight and food consumption. All yttrium-exposed offspring showed an increase in body weight on PND 21; however, no significant difference in body weight for exposed pups versus controls was observed 2 weeks or more after the yttrium solution was discontinued. The groups given 5 mg/kg daily decreased significantly in the duration of female forelime grip strength and ambulation on PND 13. There was no significant difference between yttrium-exposed offspring and controls with respect to other behavioral ontogeny parameters and postnatal behavioral test results. Conclusion Exposure of rats to yttrium nitrate in concentrations up to 45 mg/kg daily had no adverse effects on their neurobehavioral development.
文摘Objective:Moderate traumatic brain injury(TBI)can lead to a lifetime of physical,cognitive,emotional,and behavioral changes.Moreover,the secondary brain injury(SBI)during subacute and chronic phase after TBI could be blamed for these deficits.Exercise is widely recognized as promoting health and improving bad moods,but the mechanisms by which exercise affects SBI are still unclear.Methods:Lateral fluid percussion(LFP)method was used to fabricate moderate TBI in motor and somatosensory cortex of the C57 BL/6 J mice.A 4-weeks voluntary running wheel exercise with 6-day training per week was modified based on the previous protocols.Neurological status,sensorimotor function,spatial memory,electrophysiological,post-traumatic stress disorder(PTSD)associated anxiety and depression,cortical pathohistological changes were assessed to evaluate effects TBI and exercise intervention.Results:After moderate LFP injury,the TBI mice showed severe motor deficits at the early stage in acute phase but gradually recovered.During acute and subacute phase after TBI,novel object recognition(NOR)ability and spatial memory functions were consistently impaired in TBI mice;hippocampal firing frequency and burst probability were hampered.Analysis of the altered burst firing shows a clear hippocampal theta rhythm drop.These electrophysiological impacts were associated with substantially lowered NOR preference as compared with the sham group during adulthood.4-weeks voluntary wheel running performed prior to induction of a moderate TBI,combined with 2 weeks voluntary motor skill training after TBI was found to inhibit plasma TNF-α,improve locomotor activity levels,alleviate anxiety and depression and promote spatial working memory recovery in rodents.At the meantime,histopathological deterioration was eased in the hippocampus in exercised mice.Conclusion:moderate TBI could induce neurological and neurobehavior impairments in mice.Aerobic exercise rehabilitation alleviated above mentioned deficits and may be an effective supplemental invention treatment for TBI patients.
基金supported by the National Key Research and Development Program of China(No.2019YFC0408203)。
文摘Tetramethylammonium hydroxide(TMAH)is an important compound that utilized and released by the rapidly expanding semiconductor industry,which could hardly be removed by the conventional wastewater treatment techniques.As a cholinergic agonist,the tetramethylammonium ion(TMA^(+))has been reported to induce toxicity to muscular and respiratory systems of mammals and human,however the toxicity on aquatic biota remains poorly known.We investigated the neurotoxic effects of TMA^(+)exposure on zebrafish,based on neurobehavior tests and a series of biomarkers.Significant inhibitions on the swimming distance of zebrafish larvae were observed when the exposure level exceeded 50 mg/L,and significant alterations on swimming path angles(straight and deflective movements)occurred even at 10 mg/L.The tested neurobehavioral endpoints of zebrafish larvae were significantly positively correlated with reactive oxygen species(ROS)and malondialdehyde(MDA),significantly negatively related with the activities of antioxidant enzymes,but not significantly correlated with the level of acetylcholinesterase(AChE).Such relationship indicates that the observed neurotoxic effects on swimming behavior of zebrafish larvae is mainly driven by oxidative stress,rather than the alterations of neurotransmitter.At the highest exposure concentration(200 mg/L),TMA^(+)evoked more severe toxicity on zebrafish juveniles,showing significantly stronger elevation on the MDA activity,and greater inhibitions on the activities of antioxidant enzymes and ACh E,suggesting juveniles were more susceptible to TMA^(+)exposure than larval zebrafish.
基金supported by the National Key Research and Development Program of China(No.2018YFA0901103)the National Natural Science Foundation of China(No.21876196)。
文摘Tetrabromobisphenol A(TBBPA)is a widely used brominated flame retardant.There is evidence showing that TBBPA can exert thyroid disrupting effects in mammals,but different results were also reported,along with inconsistent reports regarding its neurotoxicity.Here,we investigated thyroid disrupting effects and neurotoxicity of TBBPA(5,50,500μg/(kg·day))to male mice following maternal and direct exposure through drinking water,with the antithyroid drug propylthiouracil(PTU)as the positive control.On postnatal day(PND)15,we expectedly observed severe thyroid compensatory hyperplasia and cerebellar developmental retardation in PTU-treated pups.The highest dose of TBBPA also caused thyroid histological alteration but had no effects on cerebellar development in terms of Purkinje cell morphology and the thickness of the internal granular layer and the molecular layer of the cerebellum.During puberty and adulthood,the thyroid morphological alterations became more pronounced in the TBBPA-treated animals,accompanied by decreased serum thyroid hormone levels.Furthermore,the 50 and 500μg/(kg·day)TBBPA groups showed a significant decrease in the serum level of serotonin,a neurotransmitter associated with anxiety behaviors.Correspondingly,the highest dose group displayed anxiety-like behaviors in the elevated plus-maze test on PND 35,but this neurobehavioral alteration disappeared on PND 56.Moreover,no changes in neurobehavioral parameters tested were found in TBBPAtreated animals at puberty and adulthood.Altogether,all observations show that TBBPA can exert thyroid disrupting effects but has little overt impact on brain development and neurobehaviors in mice,suggesting that thyroid disruption does not necessarily cause overtly adverse neurodevelopmental outcomes.
基金Supported by the Funds of National Basic Research Program of China(973 program,No.2010CB530500)National Natural Science Foundation of China(No.30973788)+1 种基金Guangdong province science and technology projects (No.2010B031500016)Guangdong Natural Science Foundation(No.9351040701000001)
文摘OBJECTIVE:Electroacupuncture effect on neurological behavior and the expression of tyrosine kinase Janus kinase 2(JAK 2) of ischemic cortex in rats with the focal cerebral ischemia were investigated in this study.METHODS:The model of focal cerebral ischemia was established by the heat-coagulation induced the occlusion of the middle cerebral artery.The electro-acupuncture was applied on Baihui(GV 20) and Dazhui(GV 14),and AG490 was applied by intracerebroventricular infusion.The expressions of JAK2 mRNA and phospharylatedJAK2(p-JAK2) in the ischemic cortex were observed by in situ hybridization and western blotting.RESULTS:The expressions of JAK2 mRNA and p-JAK2 were rarely found in sham surgery group.In model group,the expression of JAK2 mRNA and JAK2 phosphorylation had increased.After 1 day of cerebral ischemia,the expression had reached its peak.After cerebral ischemia,the expressions of JAK2 mRNA and p-JAK2 were consistent with the neurological deficit score.Electroacupuncture treatment and AG490 intervention were able to improve the neurological deficit score after cerebral ischemia,and down-regulate the expressions of JAK2 mRNAand JAK2 phosphorylation.CONCLUSION:After cerebral ischemia,the excessive expressions of JAK2 and the JAK2 phosphorylation would be one of mechanisms by which the brain injury got worse.The therapy of electro-acupuncture could reduce the expression of JAK2,and inhibit JAK2 phosphorylated activation,so as to block the abnormal activation of signal transduction pathway which was induced by JAK2.
基金supported by the National Natural Science Foundation of China,Nos.81802232(to JXW),81801170(to YHT),82071284(to YHT),2019YFA0112000(to YHT)the Scientific Research and Innovation Program of Shanghai Education Commission,No.2019-01-07-00-02-E00064(to GYY)+1 种基金Scientific and Technological Innovation Act Program of Shanghai Science and Technology Commission,No.20JC1411900(to GYY)Science and Technology Commission of Shanghai,No.19441907900(to JFS).
文摘Blood-brain barrier(BBB)disruption underlies the vasogenic edema and neuronal cell death induced by acute ischemic stroke.Reducing this disruption has therapeutic potential.Transcranial focused ultrasound stimulation has shown neuromodulatory and neuroprotective effects in various brain diseases including ischemic stroke.Ultrasound stimulation can reduce inflammation and promote angiogenesis and neural circuit remodeling.However,its effect on the BBB in the acute phase of ischemic stroke is unknown.In this study of mice subjected to middle cerebral artery occlusion for 90 minutes,low-intensity low-frequency(0.5 MHz)transcranial focused ultrasound stimulation was applied 2,4,and 8 hours after occlusion.Ultrasound stimulation reduced edema volume,improved neurobehavioral outcomes,improved BBB integrity(enhanced tight junction protein ZO-1 expression and reduced IgG leakage),and reduced secretion of the inflammatory factors tumor necrosis factor-αand activation of matrix metalloproteinase-9 in the ischemic brain.Our results show that low-intensity ultrasound stimulation attenuated BBB disruption and edema formation,which suggests it may have therapeutic use in ischemic brain disease as a protector of BBB integrity.
基金Youth Scientific Research Foundation of General Logistics Department of Chinese PLA,No.01Q033
文摘BACKGROUND： Several studies have demonstrated that sustained cognitive tasks can induce cognitive fatigue and that the mean cerebral blood flow velocity changes in some cerebral regions during cerebral fatigue. OBJECTIVE： To dynamically monitor the changes in mean cerebral blood flow velocity in different brain regions of high performance fighter pilots during mental arithmetic tasks and consecutive performance tasks. DESIGN, TIME AND SETTING： The present neurophysiological trial, based on controlled observation, was performed at the Laboratory of Neurophysiology, Institute of Aviation Medicine, Air Force of China between January 2003 and December 2005. PARTICIPANTS： Forty-five males, high performance fighter pilots, averaging （27.6±2.5） years, were recruited for this study. METHODS： The mean cerebral blood flow velocity in the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery of subjects was dynamically tested using transcranial Doppler during 5- hour mental arithmetic tasks and during 5- hour consecutive performance tasks. The neurobehavioral ability index was analyzed throughout each trial according to the number of correct responses, false responses, and lost responses. Simultaneously, cerebral cognitive fatigue-induced lethargy was assessed by the Stanford Sleepiness Scale. MAIN OUTCOME MEASURES： Changes in mean cerebral blood flow velocity in the anterior cerebral artery, middle cerebral artery, and posterior cerebral artery; neurobehavioral ability index of mental arithmetic and consecutive performance tasks; Stanford Sleepiness Scale scores. RESULTS： During mental arithmetic tasks, the mean cerebral blood flow velocity in the anterior cerebral artery increased during hour 2 and decreased after hour 4. There was no significant change in mean cerebral blood flow velocity in the middle cerebral artery and posterior cerebral artery. During hour 4, cerebral cognitive fatigue was observed and, simultaneously, Stanford Sleepiness Scale scores demonstrated the presence of fatigue. During such a stage, the neurobehavioral ability index decreased, indicating a decline in performance ability. During consecutive performance tasks, the mean cerebral blood flow velocity declined earlier in the posterior cerebral artery compared to the middle cerebral artery. CONCLUSION： Five- hour mental arithmetic tasks have few effects on cerebral functions and do not lead to a significant change in mean cerebral blood flow velocity. Five-hour consecutive performance tasks can induce cerebral cognitive fatigue, and a marked decline in mean cerebral blood flow velocity.
基金Supported by Development Plan (973 Plan) of National Critical and Basic Research:2006 CB 504504,2010 CB 530500
文摘OBJECTIVES:To observe recovery in movement function in rats with middle cerebral artery occlusion(MCAO) after acupuncture treatment.METHODS:According to the randomized and controlled principle 1384 rats were divided into the ba-sic control group(including the normal,sham,model control,model without intervention,Nimodipine,and para-Renzhong groups) and the acupuncture group(including the Neiguan(PC 6),Weizhong(BL 40),Sanyinjiao(SP 6),Chize(LU 5),Renzhong(GV 6) and non-acupoint groups).MCAO was modeled by Zea-longa's thread ligation and rats with scores of 1-3,as assessed by Zausinger's six-point method,were used in this study.Moreover,in the acupuncture group each acupoint was set with 12 different parameters by the orthogonal intersection method,resulting in 78 groups with 18 rats per group.The rats were treated by acupuncture once every 12 h for a total of six sessions and neurobehavioral scores were measured after each session.The neurobehavioral scores were compared by one-way ANOVA using the statistical software SPSS 17.0.RESULTS:After acupuncture therapy the mean neurobehavioral scores in MCAO rats increased gradually at each time point with a significant difference among the six scores,but with no significant differences between the fourth(48 h) and the fifth score(60 h),and between the fifth(60 h) and the sixth(72 h) score(P > 0.05).CONCLUSIONS:MCAO rats gradually recovered movement function over multiple acupuncture sessions.After the fouth acupuncture session(48 h),the neurobehavioral scores of rats with cerebral infarction remained stable.Acupuncture treatment had a reliable curative effect on movement function in cerebral infarction rats.
基金We would like to express our gratitude to Mrs.Pingping An(Wuhan Institute of Physics and Mathematics,Chinese Academy of Sciences)for her help in housing the animals.This work was supported by grants from the National Natural Science Foundation of China(8187051484,8157050329,81600933)the Interdisciplinary Medicine Seed Fund of Peking University(BMU2017MC006)the Youth Innovation Promotion Association of the Chinese Academy of Sciences,China(Y6Y0021004).
文摘Abnormal postoperative neurobehavioral performance(APNP)is a common phenomenon in the early postoperative period.The disturbed homeostatic status of metabolites in the brain after anesthesia and surgery might make a significant contribution to APNP.The dynamic changes of metabolites in different brain regions after anesthesia and surgery,as well as their potential association with APNP are still not well understood.Here,we used a battery of behavioral tests to assess the effects of laparotomy under isoflurane anesthesia in aged mice,and investigated the metabolites in 12 different sub-regions of the brain at different time points using proton nuclear magnetic resonance('H-NMR)spectroscopy.The abnormal neurobehavioral performance occurred at 6 h and/or 9 h,and recovered at 24 h after anesthesia/surgery.Compared with the control group,the altered metabolite of the model group at 6 h was aspartate(Asp),and the difference was mainly displayed in the cortex;while significant changes at 9 h occurred predominantly in the cortex and hippocampus,and the corresponding metabolites were Asp and glutamate(Glu).All changes returned to baseline at 24 h.The altered metabolic changes could have occurred as a result of the acute APNP,and the metabolites Asp and Glu in the cortex and hippocampus could provide preliminary evidence for understanding the APNP process.
文摘BACKGROUND： Previously, only single short-time low-dose hyperbaric oxygenation （HBO） protocol was administrated to treat acute ischemic stroke in early stage and the conflicting results were obtained. There are few studies to report the outcome of administering long-time （can cover all the natural pathologic progression period） high-dose HBO to treat the disease. OBJECTIVE： To evaluate the therapeutic effect between two kinds of high-dose hyperbaric oxygenation on super-early stage of acute permanent middle cerebral artery occlusion （MCAO） in rats. DESIGN： A randomized controlled experimental study. SETTING： Beijing Tiantan Hospital, Capital Medical University; Beijing Research Institute of Neurosurgery. MATERIALS： Seventy-four male SD rats, aged 2.5 months old, weighing （ 280 ＋ 20） g, were provided by the Animal Institute, Chinese Academy of Medical Sciences. Hyperbaric oxygenation device was hyperbaric air cabin in which there was a self-made pure oxygen animal experimental cabin （made in China）. METHODS： This experiment was carried out in the municipal laboratory of Beijing Tiantan Hospital affiliated to Capital Medical University and Beijing Research Institute of Neurosurgery. ① Experimental intervention： All the rats were developed into models of permanent MCAO by suture embolism. Then, they were randomly divided into two HBO groups （9 hours and 18 hours） and control group, with 24 rats in each as well as 3-hour ultrastructure control group, with 2 rats. After being modeled for 3 hours, rats in the two HBO groups stayed in the hyperbaric cabin for 9 hours and 18 hours, separately. Rats in the 9-hour HBO group inhaled pure oxygen at hours 1, 3, 5, 7 and 9, and hyperbaric air at hours 2, 4, 6 and 8. Rats in the 18-hour HBO group inhaled pure oxygen at hours l, 3, 5, 7, 9, 11, 13, 15 and 17, and hyperbaric air at hours 2, 4, 6, 8, l0 12, 14, 16 and 18. After being created into models, rats in the control group and 3-hour ultrastructure control group breathed room air. ② Experimental evaluation： Neurologic functions of rat models in the 9-hour and 18-hour HBO groups as well as control group were scored by Bederson and Garica two neurological grading systems at hours 14 and 28 and on day 5; Infarct volume of rat models in the two HBO groups and control group was measured at hour 24 and on day 5 with NIH image processing software Image J; The pathological changes of brain tissue in the brain infarct region and its opposite region of rat models in the two HBO groups and 3-hour ultrastructure control group were observed with a Philips EM 208S transmission electron microscope. MAIN OUTCOME MEASURES： ① Neurobehavioral outcome. ② Rat brain infarct volume. ③ Ultrastructure of brain tissue in the ischemic penumbra of infarct models at the different time points RESULTS： ① Neurobehavioral outcome： After treatment, Garica score in the 9-hour and 18-hour HBO groups was significantly higher than that in the control group （P 〈 0.01）. Bederson score on day 5 after modeling in the 9-hour and 18-hour HBO groups was significantly lower than that in the control group （P 〈 0.01）. ② Cerebral infarct volume： Cerebral infarct volume in the 9-hour and 18-hour HBO groups was significantly smaller than that in the control group at hour 24 and on day 5 after modeling （P 〈 0.01）. In the 18-hour HBO group, infarct volume on day 5 after modeling was significantly larger than that at hour 24 after modeling （P 〈 0.05）. ③In the 3-hour ultrastructure control group, astrocyte edema and neuron damage around the capillary in the infarct cerebral tissue significantly relieved in the rats which were subjected to HBO. CONCLUSION： High dose of HBO is highly efficient in reducing infarct volume and improving neurobehavioral outcome of rats with acute cerebral infarction, and also has an important role in inhibiting the pathological progression of ischemic brain tissue after cerebral infarction.
文摘A cross sectional epidemiological study of 93 arc welders in a shipyard was conducted to observe the adverse effect of exposure to manganese welding fumes. Among them, 37 workers with paired controls were given the neurobehavioral tests. Air concentration of manganese in working place, hair manganese and platelet 5 hydroxytryptamine in both exposed workers and controls was also measured. The higher percentage of respiratory symptoms including sour throat and dyspnea in the welders were observed as compared with the controls. The results of neurobehavioral tests showed that the welders exhibited poorer performance in simple reaction time and Santa Ana dexterity tests than that in the controls. The hair manganese concentration was higher and the blood platelet 5 HT level decreased in the welders. In conclusion, symptoms in the welders might be related to the exposure of manganese. Long term exposure to manganese welding fume could cause the change in simple reaction time and Santa Ana dexterity tests. The hair manganese concentration could be used as a biological monitoring index of exposure to manganese.
基金supported by the National Natural Science Foundation of China,No.30672684,30973722Science and Technology Support Traditional Chinese Drug Research and Development Project of Shanghai,No.F50102+1 种基金Traditional Chinese Medicine Research Fund of Shanghai Municipal Health Bureau,No.2012J009AAnnual Research Budget of Shanghai University of Traditional Chinese Medicine in 2013,No.2013JW25
文摘Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson＇s disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson＇s disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson＇s disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson＇s disease by modulating neurotransmitter signaling in the corpus striatum.
基金supported by the Hebei Province Population and the Family Planning Commission of Science and Technology Research Program in China,No.2008-B04
文摘Length and thickness of 152 corpus callosa Using ultrasonic diagnostic equipment with a were measured in neonates within 24 hours ot b^rtn. neonatal brain-specific probe, corpus callosum length and thickness of the genu, body, and splenium were measured on the standard mid-sagittal plane, and the anteroposterior diameter of the genu was measured in the coronal plane. Results showed that corpus callosum length as well as thickness of the genu and splenium increased with gesta- tional age and birth weight, while other measures did not. These three factors on the standard mid-sagittal plane are therefore likely to be suitable for real-time evaluation of corpus callosum de- velopment in premature infants using cranial ultrasound. Further analysis revealed that thickness of the body and splenium and the anteroposterior diameter of the genu were greater in male infants than in female infants, suggesting that there are sex differences in corpus callosum size during the neonatal period. A second set of measurements were taken from 40 premature infants whose ges- tational age was 34 weeks or less. Corpus callosum measurements were corrected to a gestational age of 40 weeks, and infants were grouped for analysis depending on the outcome of a neonatal behavioral neurological assessment. Compared with infants with a normal neurological assessment, corpus callosum length and genu and splenium thicknesses were less in those with abnormalities, indicating that corpus callosum growth in premature infants is associated with neurobehavioral development during the early extrauterine stage.
