Effect of tetramethylpyrazine on the spatial learning and memory function of rats after focal cerebral ischemia

BACKGROUND： Tetramethylpyrazine （TMP） presents the effect of anti-platelet aggregation, reduces arteria resistance, increases cerebral blood flow, and improves microcirculation. OBJECTIVE： To observe the effects of TMP on the learning and memory abilities and the number of neurons in cortex and hippocampus after focal cerebral ischemia in rats DESIGN： A randomized controlled tria SETTING： Department of Human Anatomy and Histological Embryology, School of Medicine, Xi＇an Jiaotong University. MATERIALS： Fifty adult male Sprague-Dawley rats, weighing 250-300 g were supplied by the Experimental Animal Center, School of Medicine, Xi＇an Jiaotong University. TMP was purchased from Wuxi Seventh Pharmaceutical Co.Ltd （Lot Number： 2004051106, Specification： 2 mL/piece）. METHODS ： The experiments were carried out in School of Medicine of Xi＇an Jiaotong University from June 2004 to May 2005. The 50 rats were randomly divided into five groups according to the random number table method： sham-operated group, cerebral ischemia control group, low-dose TMP group, middle-dose TMP group and high-dose TMP group, 10 rats in each group. Rats in the TMP groups were immediately treated with intraperitoneal injection of TMP of 40, 80 and 120 mg/kg respectively, and those in the sham-operated group and cerebral ischemia control group were injected intraperitoneally by isovolume saline, once a day for 14 days successively. On the 15^th day, the spatial learning and memory abilities of the rats were assessed with the Morris water maze test, and then the changes of neuron numbers in cortex and hippocampus were observed by Nissl staining of brain sections. MAIN OUTCOME MEASURES ： The results of Morris water maze test and the changes of neuron numbers in cortex and hippocampus by Nissl staining of brain sections were observed. RESULTS： Finally 39 rats were involved in the analysis of results, and the other 11 died of excessive anesthesia or failure in model establishment. ① The rats in the cerebral ischemia control group manifested obvious spatial cognitive deficits in the place navigation trial and spatial probe trial. The mean values of escape latency in the sham-operated group, low, middle and high-dose TMP groups were obviously shorter than that in the cerebral ischemia control group [（23.92±2.21）, （41.84±3.74）, （39.50 ±3.80）, （31.38_±3.72）, （61.60±3.61） s, P 〈 0.05-0.01]. In the spatial probe trial, significant differences in the percentage of time spending in the former platform quadrant and frequency of crossing the former platform site in the sham-operated group, lose, middle and high-dose TMP groups were obviously higher or more than those in the cerebral ischemia control group [（36.27±3.42） %, （35.84±2.54）%, （38.43±3.08）%, （36.51±1.96）%, （22.24±3.46）%; （11 ±1 ）, （10±1）, （8_±1）, （8±1）, （4±1） times, P 〈 0.01]. ② In the morphological observation, the numbers of neurons in ipsilateral （left） parietal cortex in the sham-operated group, low, middle and high-dose TMP groups were obviously more than that in the cerebral ischemia control group [（98±8）, （65±5）, （53±6）, （57±6）, （37±6）/0.625 mm^2, P 〈 0.01], but the number of neurons in left hippocampus had no obvious differences among the groups （P 〉 0.05）. CONCLUSION ： TMP can improve obviously the spatial learning and memory function after permanent focal cerebral ischemia in rats, and the neuroprotective role of the drug in cortex may be involved in its mechanism.

Memory Function and Fractional Intergral Associated to the Random Self-similar Fractal

For a physics system which exhibits memory,if memory is preserved only at points of random self-similar fractals,we define random memory functions and give the connection between the expectation of flux and the fractional integral.In particular,when memory sets degenerate to Cantor type fractals or non-random self-similar fractals our results coincide with that of Nigmatullin and Ren et al.

Correlation between special brain area and blood perfusion in patients with cerebral infarction at convalescent period Feasibility for quantitative determination and estimation of learning and memory function

BACKGROUND： Presently, clinic memory scale is used to evaluate learning memory ability in most studies, and the influence of difference in measurement condition of individuals exists. OBJECTIVE： To study the correlation between regional cerebral blood flow （rCBF） perfusion and learning memory function in special brain regions of patients with cerebral infarction at convalescent period, and to try to find out a method which can quantitatively evaluate learning ability. DESIGN： Case observation, and correlation analysis. SETTINGS： Shandong Institute for Behavioral Medicine; the Affiliated Hospital of Jining Medical College. PARTICIPANTS： Totally 70 patients with cerebral infarction admitted to Department of Neurology, Jining Medical College between January 2004 and December 2005 were involved. The involved patients, 58 male and 12 female, were averaged （52±3） years, and they were all right handed. They all met the diagnosis criteria instituted by the Fourth National Conference on Cerebrovascular Disease, and were confirmed as cerebral infarction by skull CT or MRI. Informed consents of detected items were obtained from all the patients and relatives. METHODS： When the patients were at convalescent period, their learning and memory ability were measured with “ clinic memory scale （set A）”. The 18 patients whose total mark over 100 were regarded as good learning memory function group; The 23 cases whose total mark less than 70 were regarded as poor learning memory function group. RCBF of hippocampus, nucleus amygdalae, temporal cortex and prefrontal lobe of patients between two groups were measured and compared by single photon emission computed tomography （SPECT）. The total scores of the 18 good learning memory patients and 23 poor learning memory patients were taken as dependent variable Y, and their rCBFs of hippocampus, nucleus amygdale, temporal cortex and prefrontal lobe respectively as independent variable X for linear correlation analysis. MAIN OUTCOME MEASURES： Correlation of rCBF in different brain regions and learning memory ability in patients with cerebral infarction. RESULTS： ①The rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex of good learning memory function group were significantly higher than those of poor learning memory function group （P 〈 0.05）. ②In the good learning memory function group, rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex were significantly positively correlated with memory scale scores （ r = 0.961, 0.926, 0.954, 0.907, P 〈 0.05 ） , and also in the poor learning memory function group （r = 0.979, 0.976, 0.991, 0.953, P 〈 0.05 ） . CONCLUSION： The rCBF of hippocampus, nucleus amygdale, temportal cortex and prefrontal cortex of patients with cerebral infarction are significantly positively correlated with memory scale scores. Predicting learning memory ability of patients by quantitative determination of rCBF provides a quantitative and objective method for evaluating learning memory ability.

Changes in hippocampal neurons and memory function during the developmental stage of newborn rats with hypoxic-ischemic encephalopathy

BACKGROUND: Under the normal circumstance, there exist some synapses with inactive functions in central nervous system (CNS), but these functions are activated following nerve injury. At the early stage of brain injury, the abnormal functions of brain are varied, and they have very strong plasticity and are corrected easily. OBJECTIVE: To observe the changes of neuronal morphology in hippocampal CA1 region and memory function in newborn rats with hypoxic-ischemic encephalopathy(HIE) from ischemia 6 hours to adult. DESIGN: Completely randomized grouping, controlled experiment. SETTING: Taian Health Center for Women and Children; Taishan Medical College. MATERIALS: Altogether 120 seven-day-old Wistar rats, of clean grade, were provided by the Experimental Animal Center, Shandong University of Traditional Chinese Medicine. Synaptophysin (SYN) polyclonal antibody was provided by Maixin Biological Company, Fuzhou. METHODS: This experiment was carried out in the Laboratory of Morphology, Taishan Medical College between October 2000 and December 2003. ① The newborn rats were randomly divided into 2 groups: model group and control group, 60 rats in each group. Five rats were chosen from each group at postoperative 6 hours, 24 hours, 72 hours, 7 days, 2 weeks and 3 weeks separately for immunohistochemical staining. Fifteen newborn rats were chosen from each group at postoperative 4 weeks and 2 months separately for testing memory ability (After test, 5 rats from each group were sacrificed and used for immunohistochemical staining)② The right common carotid artery of newborn rats of model group was ligated under the anesthetized status. After two hours of incubation, the rats were placed for 2 hours in a container filled with nitrogen oxygen atmosphere containing 0.08 volume fraction of oxygen, thus, HIE models were created; As for the newborn rats in the control group, only blood vessels were isolated, and they were not ligated and hypoxia-treated. ③ Thalamencephal tissue sections of newborn rats of two groups were performed DAB developing and haematoxylin slight staining. Cells with normal nucleous in 250 μm-long granular layer which started from hippocampal CA1 region were counted with image analysis system under high-fold optical microscope (×600), and the thickness of granular layer was measured. The absorbance (A) of positive reactant of SYN in immunohistochemically-stained CA1 region was measured. Learning and memory ability were measured with step through test 3 times successively. ④ t test and paired t test were used for comparing intergroup and intragroup difference of measurement data respectively, and Chi-square for comparing the difference of enumeration data. MAIN OUTCOME MEASURES: Comparison of cytological changes in hippocampal CA1 region and memory ability at different postoperative time points between two groups. RESULTS: Totally 120 newborn rats were involved in the result analysis. ① Cell morphological changes in hippocampal CA1 region: In the control group, with aging, perikaryon, nucleus and nucleolus in cortex of parietal lobe were significantly increased, Nissl body was compacted, the amount of neurons was declined, but the A of SYN positive reactant was relatively increased. In the model group, at postoperative each time point, neurons were seriously shrunk and dark-stained, nucleus was contracted, chromatin was condensed, nucleolus was unclear, even cells disappeared, especially the cells in 6 hours and 24 hours groups. The amount of neurons with normal morphology in hippocampal CA1 region and granular layer thickness in the model group at postoperative each time point were significantly less or smaller than those in the control group at postoperative 6 hours respectively (t =3.002-1.254, P < 0.01). The A value of SYN positive reactant at postoperative 2, 3 and 4 weeks was significantly higher than that at previous time point (t =2.011-2.716,P < 0.05-0.01). ② Test results of learning and memory ability: In the first test, there was no significant difference in the ratio of rats which kept memory ability between two groups (P > 0.05); In the third test, the ratio of rats which kept memory ability in the model group was significantly lower than that in the control group at postoperative 4 weeks and 2 months[53%(8/15),100%(15/15);60%(9/15),93%(14/15),χ 2=2.863,2.901,P < 0.01]. CONCLUSION: The destroyed hippocampal structure induces the decrease of learning and memory ability of developmental rats. Early interference can increase the quality of neurons and also promote functional development of the nervous system.

Exercise preconditioning alleviates ischemia-induced memory deficits by increasing circulating adiponectin

Cerebral ischemia is a major health risk that requires preventive approaches in addition to drug therapy.Physical exercise enhances neurogenesis and synaptogenesis,and has been widely used for functional rehabilitation after stroke.In this study,we determined whether exercise training before disease onset can alleviate the severity of cerebral ischemia.We also examined the role of exercise-induced circulating factors in these effects.Adult mice were subjected to 14 days of treadmill exercise training before surgery for middle cerebral artery occlusion.We found that this exercise pre-conditioning strategy effectively attenuated brain infarct area,inhibited gliogenesis,protected synaptic proteins,and improved novel object and spatial memory function.Further analysis showed that circulating adiponectin plays a critical role in these preventive effects of exercise.Agonist activation of adiponectin receptors by Adipo Ron mimicked the effects of exercise,while inhibiting receptor activation abolished the exercise effects.In summary,our results suggest a crucial role of circulating adiponectin in the effects of exercise pre-conditioning in protecting against cerebral ischemia and supporting the health benefits of exercise.

Effects of Bushen Huoxue Formula on the Learning and Memory Function and the Cerebral Neurotransmitters in Diabetic Mice

Objective: To observe the effects of Bushen Huoxue Formula (Formula for reinforcing the kidney and activating blood circulation) on the learning and memory function and the cerebral neurotransmitters in diabetic mice. Methods: Forty ICR mice were randomized into the normal control group, model group, Nimotop group and Chinese medicine group, 10 mice in each group. Tail intravenous injection of alloxan was applied to prepare diabetic model. Four weeks later, intragastric administration of Bushen Huoxue Formula for the Chinese medicine group, Nimotop for the Nimotop group, and isometric distilled water for the other two groups were respectively given for 8 weeks. The changes in the blood sugar level were observed; the learning and memory function was detected by Morris labyrinth test; and the contents of norepinephrine (NE), dopamine (DA), 5-hydroxyltryptamine (5-HT) and 5-hydroxyl indole acetic acid (5-HIAA) in cerebral cortex were determined in mice of all the groups. Results: The blood sugar levels in the diabetic model mice significantly increased as compared with those of the normal control group determined 72 h and 12 weeks later (P<0.05 or P<0.01). Latencies for Morris labyrinth test in the Nimotop group and the Chinese medicine group were significantly shortened as compared with that in the model group (P<0.01). The contents of cortical NE in the Chinese medicine group was significantly higher than that in the model group (P<0.01). Conclusion: Bushen Huoxue Formula can improve the learning and memory function in the diabetic mice, and the mechanism is possibly related with change of the cortical NE content.

Effects of special brain area regional cerebral blood flow abnormal perfusion on learning and memory function and its molecular mechanism in rats

To study the effect of special brain area regional cerebral blood flow(rCBF)abnormal perfusion on learning and memory function and its molecular mechanism,64 adult male healthy Sprague-Dawley(SD)rats were randomly divided into two groups,the false operation group(control group)and the operation group(model group).After surgical operation,the operation group undertook bilateral common carotid artery permanent ligation,while the other group did not.Learning and memory function were measured by Y-maze at 4 h,8 h,24 h and 3 d after surgical operation,respectively.The rCBF of the right frontal lobe and hippocampus was also detected by the PerifluxPF model laser Doppler flowmetry,and the expressions of c-fos or c-jun or Bcl-2 and Bax were also measured by immune histochemistry S-P method accordingly.Results showed that the rCBF of the right frontal lobe and hippocampus in the operation group was significantly lower than that in the false operation group(P,0.05).The learning indexes,error number(EN),day of reach standard and total reaction time(TRT)in the operation group,were significantly higher than that in the false operation group(P,0.05).However,the initiative evasion rate in the operation group was significantly lower than that in the false operation group.The study also found that the rCBF was relatively more,the indexes(EN,the day of reach standard and TRT)relatively fewer,but the initiative evasion rate and the memory keeping rate were relatively more.The positive expression and the average absorbency of Fos and Jun in the operation group were significantly higher than that in the false operation group(P<0.05).Furthermore,Bax and Bcl-2 positive cells were all increased over time in the operation group,and the expression ratio of Bax/Bcl-2 in the operation group was significantly higher than that in the false operation group(P<0.01).In conclusion,rCBF decrease can impair the learning and memory function in rats,which may be related to the increase of the expression ratio of c-fos or c-jun or Bcl-2 or Bax in the frontal cortex and hippocampus.

Effect of Cistanche Desertica Polysaccharides on Learning and Memory Functions and Ultrastructure of Cerebral Neurons in Experimental Aging Mice

To observe the effects of Cistanche desertica polysaccharides (CDP) on the learning and memory functions and cerebral ultrastructure in experimental aging mice. Methods: CDP was administrated intragastrically 50 or 100 mg/kg per day for 64 successive days to experimental aging model mice induced by D-galactose, then the learning and memory functions of mice were estimated by step-down test and Y-maze test; organelles of brain tissue and cerebral ultrastructure were observed by transmission electron microscope and physical strength was determined by swimming test. Results: CDP could obviously enhance the learning and memory functions (P＜0.01) and prolong the swimming time (P＜0.05), decrease the number of lipofuscin and slow down the degeneration of mitochondria in neurons(P＜0.05), and improve the degeneration of cerebral ultra-structure in aging mice. Conclusion: CDP could improve the impaired physiological function and alleviate cerebral morphological change in experimental aging mice.

Tongdu Tiaoshen Acupuncture Method for Promoting Hippocampal Nerve Repair and Regeneration and Improving Learning and Memory Dysfunction in Stroke Model Rats

[Objectives]To evaluate the effects of Tongdu Tiaoshen Acupuncture method on improving learning and memory function and hippocampal nerve regeneration and repair after stroke.[Methods]Animal models of cognitive impairment in the recovery phase of cerebral infarction in rats were prepared,and rats were randomly divided into control group,model group,donepezil group,and acupuncture group.Morris water maze experiment was carried out to evaluate learning and memory ability.Nissl staining,BrdU and DCX immunofluorescence staining were used to observe the number and morphological structure of neuronal pyramidal and granular cells in the dentate gyrus(DG)area of the hippocampus,as well as the proliferation and differentiation of neural progenitor cells.TUNEL method was used to detect cell apoptosis.[Results]Before intervention,the scores and ELP of the model group,donepezil group and acupuncture group were significantly higher than those of the blank group(P<0.05);after the intervention,the neurological scores and ELP of the blank group and the model group were not significantly different from those before the intervention(P<0.05);the donepezil group and acupuncture group were significantly reduced,there was no difference between the donepezil group and acupuncture group(P>0.05),but it was still significantly higher than the blank group(P<0.05).The results of BrdU and DCX immunofluorescence staining showed that there were only a few BrdU positive cells and DCX protein in the hippocampal DG area of mice in the blank group,and the positive cells in the model group were significantly increased(P<0.05);donepezil group and acupuncture group showed significant increase compared with the model group(P<0.05);compared with the blank group,the number of neurons in the hippocampal DG area of each group was significantly reduced(P<0.01),and the neuronal apoptosis index was significantly increased(P<0.01);compared with the blank group,the number of neurons in the hippocampal DG area of each group was significantly reduced(P<0.01),and the neuronal apoptosis index was significantly increased(P<0.01).The number of neurons in the hippocampal DG area of rats in the acupuncture group and donepezil group was significantly increased(P<0.01),and the neuronal apoptosis index was significantly decreased(P<0.01).[Conclusions]Tongdu Tiaoshen Acupuncture method can improve the learning and memory function of stroke model rats by promoting the regeneration and repair of hippocampal nerve in rats with cerebral infarction.

Hippocampal resting-state functional connectivity with the mPFC and DLPFC moderates and mediates the association between education level and memory function in subjective cognitive decline

Objective:This study aims to determine the relationship between education level,memory function,and hippocampus functional and structural alterations in subjective cognitive decline(SCD).Methods:Seventy-five participants with SCD were divided into high education(HE)and low education(LE)level groups.A Wechsler Memory Scale-Chinese Revision test and functional and structural MRI were performed within 1 week after participant recruitment.The bilateral hippocampus resting-state functional connectivity(rsF C),gray matter volume(GMV)of brain regions identified by rsF C analysis,and moderating and mediating effects were assessed.Results:Compared with the LE group,HE individuals showed 1)higher memory quotient(MQ)and Digit Span subscore,2)decreased hippocampal rs FC with the right medial prefrontal cortex(mPFC)and dorsolateral prefrontal cortex(DLPFC),and 3)increased GMV in the right mP FC and DLPFC.The bilateral hippocampus-right DLPFCrs FC significantly associated with the MQ and the bilateral hippocampus-right m PFCrs FC with the Digit Span subscore in each group.The bilateral hippocampus-right DLPFCrsFC moderated the relationship between the education level and MQ.The bilateral hippocampus-right mP FC rsF C mediated the relationship between the education level and Digit Span subscore in all subjects.Conclusion:The hippocampal rsF C with the right mP FC and DLPFC contributes to the education level effect on memory function in SCD.

Improvement of learning and memory abilities and motor function in rats with cerebral infarction by intracerebral transplantation of neuron-like cells derived from bone marrow stromal cells

BACKGROUND： Transplantation of fetal cell suspension or blocks of fetal tissue can ameliorate the nerve function after the injury or disease in the central nervous system, and it has been used to treat neurodegenerative disorders induced by Parkinson disease. OBJECTIVE： To observe the effects of the transplantation of neuron-like cells derived from bone marrow stromal cells （rMSCs） into the brain in restoring the dysfunctions of muscle strength and balance as well as learning and memory in rat models of cerebral infarction. DESIGN ： A randomized controlled experiment.SETTING ： Department of Pathophysiology, Zhongshan Medical College of Sun Yat-sen University.MATERIALS ： Twenty-four male SD rats （3-4 weeks of age, weighing 200-220 g） were used in this study （Certification number：2001A027）. METHODS： The experiments were carried out in Zhongshan Medical College of Sun Yat-sen University between December 2003 and December 2004. ① Twenty-four male SD rats randomized into three groups with 8 rats in each： experimental group, control group and sham-operated group. Rats in the experiment al group and control group were induced into models of middle cerebral artery occlusion （MCAO）. After in vitro cultured, purified and identified with digestion, the Fischer344 rMSCs were induced to differentiate by tanshinone IIA, which was locally injected into the striate cortex （18 area） of rats in the experimental group, and the rats in the control group were injected by L-DMEM basic culture media （without serum） of the same volume to the corresponding brain area. In the sham-operated group, only muscle and vessel of neck were separated. ② At 2 and 8 weeks after the transplantation, the rats were given the screen test, prehensile-traction test, balance beam test and Morris water-maze test. ③ The survival and distribution of the induced cells in corresponding brain area were observed with Nissl stained with toluidine blue and hematoxylin and eosin （HE） staining in the groups.MAIN OUTCOME MEASURES ： ① Results of the behavioral tests （time of the Morris water-maze test screen test, prehensile-traction test, balance beam test）; ② Survival and distribution of the induced cells.RESULTS： All the 24 rats were involved in the analysis of results. ① Two weeks after transplantation, rats with neuron-like cells grafts in the experimental group had significant improvement on their general muscle strength than those in the control group [screen test： （9.4±1.7）, （4.7±1.0） s, P 〈 0.01]; forelimb muscle strength [prehensile-traction test： （7.6±1.4）, （5.2±1.2） s, P 〈 0.01], ability to keep balance [balance beam test： （7.9±0.74）, （6.1±0.91） s, P 〈 0.01] and abilities of learning and memory [latency to find the platform： （35.8±5.9）, （117.5±11.6） s, P 〈 0.01; distance： （623.1±43.4）, （1 902.3±98.6） cm, P 〈 0.01] as compared with those in the control group. The functional performances in the experimental group at 8 weeks were better than those at two weeks, which were still obviously different from those in the sham-operated group （P 〈 0.05）. ② The HE and Nissl stained brain tissue section showed that there was nerve cell proliferation at the infarcted cortex in the experiment group, the density was higher than that in the control group, plenty of aggregative or scattered cells could be observed at the site where needle was inserted for transplantation, the cells migrated directively towards the area around them, the cerebral vascular walls were wrapped by plenty of cells; In the control group, most of the cortices were destroyed, karyopyknosis and necrosis of neurons were observed, normal nervous tissue structure disappeared induced by edema, only some nerve fibers and glial cells remained.CONCLUSION： The rMSCs transplantation can obviously enhance the motor function and the abilities of learning and memory in rat models of cerebral infarction.

Effects of repetitive transcranial magnetic stimulation on cognitive function and cholinergic activity in the rat hippocampus after vascular dementia

Repetitive transcranial magnetic stimulation （rTMS） is a non-invasive treatment that can enhance the recovery of neurological function after stroke. Whether it can similarly promote the recovery of cognitive function after vascular dementia remains unknown, In this study, a rat model for vascular dementia was established by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were ad- ministered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic field intensity of 1,33 T. The Morris water maze test was used to evaluate learning and memory function. The Karnovsky-Roots method was performed to determine the density of cholinergic neurons in the hippocampal CA1 region. Immunohistochemical staining was used to determine the number of brain-derived neurotroph- ic factor （BDNF）-immunoreactive cells in the hippocampal CA1 region, rTMS treatment for 30 days significantly improved learning and memory function, increased acetylcholinesterase and choline acetyltransferase activity, increased the density of cholinergic neurons, and increased the number of BDNF-immunoreactive cells. These results indicate that rTMS can ameliorate learning and memory deficiencies in rats with vascular dementia, The mechanism through which this occurs might be related to the promotion of BDNF expression and subsequent restoration of cholinergic system activity in hippocampal CA 1 region.

DL-3-n-butylphthalide improved physical and learning and memory performance of rodents exposed to acute and chronic hypobaric hypoxia

Background:Studies have revealed the protective effect of DL-3-n-butylphthalide(NBP)against diseases associated with ischemic hypoxia.However,the role of NBP in animals with hypobaric hypoxia has not been elucidated.This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.Methods:Sprague-Dwaley rats and Kunming mice administered with NBP(0,60,120,and 240 mg/kg for rats and 0,90,180,and 360 mg/kg for mice)were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined.Then,the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments,conducted at 5800 m for 3 days or 20 days,to evaluate changes in physical functions.The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment,conducted at 5800 m for 6 days or 27 days,to evaluate changes in learning and memory function.ATP levels were measured in the gastrocnemius muscle and malonaldehyde(MDA),superoxide dismutase(SOD),hydrogen peroxide(H_(2)O_(2)),glutathione peroxidase(GSH-Px),and lactate were detected in sera of rats,and routine blood tests were also performed.Results:Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability.The time and distance to exhaustion for mice(NBP,90 mg/kg)and time to exhaustion for rats(NBP,120 and 240 mg/kg)significantly increased under conditions of acute hypoxia compared with control group.NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia.Moreover,240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia.Furthermore,the levels of MDA and H_(2)O_(2) decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia.Additionally,ATP levels in the gastrocnemius muscle significantly increased,while lactate levels in sera significantly decreased.Conclusion:NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.

Individuals with and without normal tension glaucoma exhibit comparable performance on tests of cognitive function

AIM:To evaluate aspects of cognition impacted by individuals with and without normal tension glaucoma.METHODS:Fifty normal tension glaucoma(NTG)and 50 control patients≥50 y of age were recruited from the UCSF Department of Ophthalmology.Demographic data and glaucoma parameters were extracted from electronic medical records for both groups.Tests of executive function[Executive Abilities:Measures and Instruments for Neurobehavioral Evaluation and Research(EXAMINER)]and learning and memory[California Verbal Learning Test–Second Edition(CVLT-II)]were administered to both NTG and controls.Race,handedness,best-corrected visual acuity,maximum intraocular pressure,optic nerve cup-todisc ratio,visual field and optic nerve optical coherence tomography parameters,and a measure of general health(Charlson Comorbidity Index)were compared between NTG and controls as well as within NTG subgroups.Multivariate linear regression was used to compare group performances on the EXAMINER battery and CVLT-II while controlling for age,sex,and years of education.RESULTS:NTG and controls were comparable with respect to age,sex,race,education,handedness,and the Charlson Comorbidity Index(P>0.05 for all).Performance on the EXAMINER composite score and the CVLT-II did not differ between NTG and controls(P>0.05 for both).CONCLUSION:This is the first prospective study in which the cognitive function of subject with NTG were evaluated using a comprehensive,computerized neurocognitive battery.Subjects with NTG do not perform worse than unaffected controls on tests of executive function,learning,and memor y.Results do not suppor t the hypothesis that individuals with NTG are at higher risk for cognitive dysfunction and/or dementia.

Formation mechanism of inherent spatial heterogeneity of microstructure and mechanical properties of NiTi SMA prepared by laser directed energy deposition

Ni51Ti49 at.%bulk was additively manufactured by laser-directed energy deposition(DED)to reveal the microstructure evolution,phase distribution,and mechanical properties.It is found that the localized remelting,reheating,and heat accumulation during DED leads to the spatial heterogeneous distribution of columnar crystal and equiaxed crystal,a gradient distribution of Ni4Ti3 precipitates along the building direction,and preferential formation of Ni4Ti3 precipitates in the columnar zone.The austenite transformation finish temperature(Af)varies from-12.65℃(Z=33 mm)to 60.35℃(Z=10 mm),corresponding to tensile yield strength(σ0.2)changed from 120±30 MPa to 570±20 MPa,and functional properties changed from shape memory effect to superelasticity at room temperature.The sample in the Z=20.4 mm height has the best plasticity of 9.6%and the best recoverable strain of 4.2%.This work provided insights and guidelines for the spatial characterization of DEDed NiTi.

The potential of endogenous neurogenesis for brain repair and regeneration following traumatic brain injury

Traumatic brain injury （TBI） is the leading cause of death and disability of persons under 45 years old in the United States, affecting over 1.5 million individtials each year. It had been th ought that recovery from such injuries is severely limited due to the inability of the adult bra in to replace damaged neurons. However, recent studies indicate that the mature mammalian central nervous system （CNS） has the potential to replenish damaged neurons by proliferation and neuronal differentiation of adult neural stem/progenitor cells residing in the neurogenic regions in the brain. Furthermore, increasing evidence indicates that these endogenous stem/ progenitor cells may play regenerative and reparative roles in response to CNS injuries or diseases. In support of this notion, heightened levels of cell proliferation and neurogenesis have been ob- served in response to brain trauma or insults suggesting that the brain has the inherent potential to restore populations of damaged or destroyed neurons. This review will discuss the potential functions of adult neurogenesis and recent development of strategies aiming at harnessing this neurogenic capacity in order to repopulate and repair the injured brain.

Clinical Research on Comprehensive Treatment of Senile Vascular Dementia

Objective:To observe the curative effect of combined Chinese medicine,acupuncture and rehabilitation therapy on vascular dementia(VD),and to compare the Western medicine piracetam.Methods:Total 134 VD patients screened in reference to the standard for VD diagnosis in DSM-IV were randomly divided into a Chinese medicine plus rehabilitation group(32 cases),a Chinese medicine plus acupuncture group(33 cases),a Chinese medicine and acupuncture plus rehabilitation group(37 cases) and a Western medicine piracetam group(32 cases).Mini Mental State Examination(MMSE) and Bless Behavior Scale(BBS) were used to assess changes in intelligence disorder before treatment and after 12-week treatment.Results:BBS score,living ability and daily habit were enhanced after treatment in all groups.Cognitive function and behavioral ability were improved with similar total curative effects in all the 4 groups.Directional ability and short-term memory ability were significantly enhanced after treatment(P<0.05) in both the Chinese medicine plus rehabilitation group and the Chinese medicine plus acupuncture group groups.Living ability was significantly improved after treatment in the Chinese medicine and acupuncture plus rehabilitation group(P<0.01).However,no obvious difference was shown before and after treatment in the piracetam group.Conclusion:The improvement of living ability in the comprehensive treatment group is better than that in the other groups.Chinese medicine and acupuncture plus rehabilitation treatment can improve intelligence and living ability of senile VD patients.

Effect of Modified Wuzi Yanzong Granule(加味五子衍宗颗粒)on Patients with Mild Cognitive Impairment from Oxidative Damage Aspect

Objective： To observe the effects of modified Wuzi Yanzong Granule （加味五子衍宗颗粒,WYG） on memory function and the activity of serum superoxide dismutase （SOD）, malondialdehyde （MDA） levels, leukocyte mitochondrial DNA （mtDNA） deletion rate and β-amyloid protein1.28 （A β 1-28 ） in patients with mild cognitive impairment （MCl）. Methods： Thirty-six patients with MCl were selected based on the internationally recognized Petersen＇s criteria, and equally and randomly assigned to two groups. The treated group was treated with WYG and the control group was treated with placebo for 3 months. In addition, 20 healthy subjects were included in the study as the normal control group. Changes of memory function, SOD activity, MDA content, leukocyte mtDNA deletion rate and A β 1-28 content were observed before and after treatment. Results： Compared with the normal control group, the memory quotient and SOD activity in patients with MCl decreased significantly （P 〈 0.01）, while MDA, A β1-28 levels and the leukocyte mtDNA deletion rate increased significantly （P 〈 0.01）. After treatment, levels of memory quotient and serum SOD activity increased while the serum MDA level, leukocyte mtDNA deletion rate and A β 1-28 level decreased in the treated group compared with those before treatment （P〈0.01, P〈0.05）. Meanwhile, leukocyte mtDNA deletion rate and A β 1-28 content in the treated group were all lower than those in the control group （P〈0.05）. Conclusion： WYG could improve memory function in patients with MCl and the therapeutic mechanism is possibly related to the increased activity of anti-oxidase, the improved free radical metabolism and the alleviation of leukocyte mtDNA oxidation damage. WYG shows clinical significance in delaying the progression of MCl.

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

Impaired structure and function of the hippocampus is a valuable predictor of progression from amnestic mild cognitive impairment（a MCI） to Alzheimer＇s disease（AD）. As a part of the medial temporal lobe memory system,the hippocampus is one of the brain regions affected earliest by AD neuropathology,and shows progressive degeneration as a MCI progresses to AD. Currently,no validated biomarkers can precisely predict the conversion from a MCI to AD. Therefore,there is a great need of sensitive tools for the early detection of AD progression. In this review,we summarize the specifi c structural and functional changes in the hippocampus from recent a MCI studies using neurophysiological and neuroimaging data. We suggest that a combination of advanced multi-modal neuroimaging measures in discovering biomarkers will provide more precise and sensitive measures of hippocampal changes than using only one of them. These will potentially affect early diagnosis and disease-modifying treatments. We propose a new sequential and progressive framework in which the impairment spreads from the integrity of fibers to volume and then to function in hippocampal subregions. Meanwhile,this is likely to be accompanied by progressive impairment of behavioral and neuropsychological performance in the progression of a MCI to AD.