Relationship of cerebral arterial stenosis to cognitive and memory disorders

BACKGROUND: Cerebral arterial stenosis can cause cerebral hypoperfusion, and than result in the decline of cognitive function, whereas the cognitive dysfunction induced by different cerebral arterial stenosis have different manifestations and types. OBJECTIVE: To observe the differences of cognitive and memory dysfunctions in patients with cerebral arterial stenosis of different types. DESIGN: A comparative observation. SETTING: Affiliated Hospital of Jining Medical College. PARTICIPANTS: Forty-two outpatients or inpatients with cerebral arterial stenosis were selected from the Department of Neurology, Affiliated Hospital of Jining Medical College from February 2005 to January 2006, including 25 males and 17 females. There were 18 cases of internal carotid arterial stenosis, 14 cases of vertebrobasilar arterial stenosis and 10 cases of whole cerebral arterial stenosis. The diagnostic standards for cerebral arterial stenosis were identified according to North American Symptomatic Carotid Endarterectomy Trial (NASCET). Meanwhile, 18 healthy physical examinees were enrolled as the control group, including 10 males and 8 females, aged 58-80 years old. All the enrolled subjects were informed and agreed with the detection and evaluation. METHODS: ① The memory function was evaluated using revised Wechsler memory scale for adults, including long-term memory (experience, orientation and counting), short-term memory (visual recognition, picture memory, visual regeneration, association and thigmesthesia) and sensory memory (forward and backward recitation of numbers). The scale scores were turned to memory quotients. The higher the scores, the better the memory function. ② The cognitive function was evaluated using revised Wechsler adult intelligence scale: It consisted of eleven subtests, including six language scales (information, digit span, vocabulary, arithmetics, apprehension, similarity) and five operation scales (picture completion, picture arrangement, block design, geometric design, digit-symbol test). The intelligence quotients were obtained. The higher the scores, the better the cognitive function. MAIN OUTCOME MEASURES: Results of memory and cognitive function test in patients with cerebral arterial stenosis of different types. RESULTS: All the 42 patients with cerebral artery stenosis and 11 healthy subjects were involved in the final analysis of results. ① Results of memory function test: The memory function was worse in the arterial stensis groups than in the control group (P < 0.05-0.01). There were very significant differences in the scores of orientation, association and picture memory between the internal carotid arterial stenosis group and control group (P < 0.01). There were also very significant differences in the scores of counting, logic memory, forward and backward recitation of numbers, visual regeneration, visual recognition and thigmesthesia between the vertebrobasilar arterial stenosis group and control group (P < 0.01). Except experience and visual regeneration, there were significant very differences in the scores of the other tests between the whole cerebral arterial stenosis group and control group (P < 0.01). The memory quotient was obviously lower in the vertebrobasilar arterial stenosis group than in the internal carotid arterial stenosis group [(72.31±26.46), (87.38±21.86) points, P < 0.05], and it was the lowest in the whole cerebral arterial stenosis group [(63.74±25.25) points]. ② Results of cognitive function test: The cognitive function was worse in the arterial stensis groups than in the control group (P < 0.05-0.01). There were very significant differences in the scores of apprehension, arithmetics, similarity, digit-symbol test, picture completion and block design between the internal carotid arterial stenosis group and control group (P < 0.01). There were also very significant differences in the scores of backward recitation of numbers, vocabulary and geometric design between the vertebrobasilar arterial stenosis group and control group (P < 0.01). Except information, there were significant very differences in the scores of the other tests between the whole cerebral arterial stenosis group and control group (P < 0.01). The intelligence quotient was obviously lower in the internal carotid arterial stenosis group than in the vertebrobasilar arterial stenosis group [(72.65±23.39), (81.34±25.46) points, P < 0.05], and it was the lowest in the whole cerebral arterial stenosis group [(65.98±27.34) points]. CONCLUSION: Different cerebral arterial stenosis can induce different cognitive dysfunctions. The main manifestation of the patients with internal carotid arterial stenosis was the declined cognitive function, and that in patients with vertebrobasilar arterial stenosis was the declined memory, and the decrease of total intelligence was more obvious in the formers than in the latters, whereas the decrease of total memory quotient was more obvious in the patients with vertebrobasilar arterial stenosis; The cognitive and memory dysfunction were the most serious in patients with whole cerebral arterial stenosis.

Agomelatine:a potential novel approach for the treatment of memory disorder in neurodegenerative disease

Agomelatine is a selective agonist of melatonin receptor 1A/melatonin receptor 1B(MT/MT)and antagonist of 5-hydroxytryptamine 2C receptors.It is used clinically to treat major depressive episodes in adults.The pro-chronobiological activity of agomelatine reconstructs sleep-wake rhythms and normalizes circadian disturbances via its agonistic effect of melatonin receptor 1A/melatonin receptor 1B,which work simultaneously to counteract depression and anxiety disorder.Moreover,by antagonizing neocortical postsynaptic 5-hydroxytryptamine 2C receptors,agomelatine enhances the release of dopamine and noradrenaline in the prefrontal cortex,increases the activity of dopamine and noradrenaline,and thereby reduces depression and anxiety disorder.The combination of these two effects means that agomelatine exhibits a unique pharmacological role in the treatment of depression,anxiety,and disturbance of the circadian rhythm.Emotion and sleep are closely related to memory and cognitive function.Memory disorder is defined as any forms of memory abnormality,which is typically evident in a broad range of neurodegenerative diseases,including Alzheimer’s disease.Memory impairment and cognitive impairment are common symptoms of neurodegenerative and psychiatric diseases.Therefore,whether agomelatine can improve memory and cognitive behaviors if used for alleviating depression and circadian-rhythm sleep disorders has become a research“hotspot”.This review presents the latest findings on the effects of agomelatine in the treatment of psychologic and circadian-rhythm sleep disorders in clinical trials and animal experiments.Our review evaluates recent studies on treatment of memory impairment and cognitive impairment in neurodegenerative and psychiatric diseases.

Effect of Batroxobin on Expression of Neural Cell Adhesion Molecule in Temporal Infarction Rats and Spatial Learning and Memory Disorder

The effect of Batroxobin expression of neural cell adhesion molecule (NCAM) in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemical methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats and at the same time NCAM expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of NCAM immune reactive cells of Batroxobin-treated rats was more than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats and the regulation of the expression of NCAM is probably related to the neuroprotective mechanism.

Effects of Batroxobin on Spatial Learning and Memory Disorder of Rats with Temporal Ischemia and the Expression of HSP32 and HSP70

The effect of Batroxobin on spatial memory disorder of left temporal ischemic rats and the expression of HSP32 and HSP70 were investigated with Morri`s water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats in searching a goal were significantly longer than those of the sham-operated rats and at the same time HSP32 and HSP70 expression of left temporal ischemic region in rats was significantly increased as compared with the sham-operated rats. However, the mean reaction time and distance of the Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of HSP32 and HSP70 immune reactive cells of Batroxobin-treated rats was also less than that of the ischemic group. In conclusion, Batroxobin can improve spatial memory disorder of temporal ischemic rats; and the down-regulation of the expression of HSP32 and HSP70 is probably related to the attenuation of ischemic injury.

Effect of Batroxobin on Expression of C-Jun in Left Temporal Ischemic Rats with Spatial Learning and Memory Disorder

The effect of Batroxobin on expression of c-Jun in left temporal ischemic rats with spatial memory disorder was investigated by means of Morri's water maze and immunohistochemistry methods. The results showed that the mean reaction time and distance of temporal ischemic rats for searching a goal were significantly longer than those of sham-operated rats, and at the same time c-Jun expression of left temporal ischemic region was significantly increased. However, the mean reaction time and distance of Batroxobin-treated rats were shorter and they used normal strategies more often and earlier than those of ischemic rats. The number of c-Jun immune reactive cells of Batroxobin-treated rats was also less than that of ischemic group. In conclusion, Batroxobin can improve spatial memory disorder in temporal ischemic rats, and the down-regulation of the expression of c-Jun is probably related to the neuroprotective mechanism.

Correlations between Event-related Potentials with Pictures Recognition and WMS-RC Scores in Patients with Memory Disorder Caused by Severe Traumatic Brain Injury

This study explored the possibility of using event-related potentials （ERP） for the measurement of picture-recognition memory and examined its correlation with the Chinese Wechsler Memory Scale-revised （WMS-RC） in patients with memory disorder caused by severe traumatic brain injury （sTBI）. The subjects included 20 sTBI patients with memory disorder and 22 healthy individuals. Memory function was measured by using WMS-RC. Behavioral and ERP responses were recorded on-line during performance on a battery of picture recognition and the responses were analyzed off-line for recognition memory effects. Mean memory quotient （MQ） of patients with sTBI was significantly lower than that of the control group. Mean reaction time （RT） was significantly longer and the mean correctness rate （CR） of picture recognition was significantly lower in sTBI group than that of the controls. In controls, the main components of average ERP of picture recognition includes two positive-going waves, designated as P170 and P500, that appear 170 ms and 500 ms after stimulation when the subject could later successfully recall and recognize the pictures. P500 amplitude of target stimulus was significantly higher than that of non-target stimulus. Compared to controls, P500 responses of sTBI group were significantly delayed in latency （P〈0.001） and lower in amplitude （P〈0.001）. P500 latency showed significant negative correlation with MQ and the scores of ＂addition＂, ＂visual recognition＂, ＂picture recall＂, ＂visual reproduction＂ and ＂tactile memory＂ in WMS-RC. ERP of picture recognition provides a neurophysiological approach to directly assess memory impairment, and P500 may serve as a helpful index for memory disorder caused by sTBI in forensic practice.

Effects of Yizhi Capsule (益智胶囊) on Learning and Memory Disorder and β-amyloid Peptide Induced Neurotoxicity in Rats

To explore the effects of Yizhi Capsule （益智胶囊, YZC） on learning and memory disorder and β-amyloid peptide induced neurotoxicity in rats. Methods： Various doses of YZC were administered to Sprague-Dawley （SD） rats for 8 consecutive days, twice a day. On the 8th day of the experiment, scopolamine hydrobromide was intraperitoneally injected to every rat and Morris water maze test and shuttle dark avoidance test were carried out respectively to explore the changes of learning and memory capacities in the rats. Resides, after the cerebral cortical neurons of newborn SD rats aged within 3 days were cultured in vitro for 7 days, drug serum containing YZC was added to the cultured neurons before or after β amyloid peptide25-35 （Aβ25-35） intoxication to observe the protective effect of YZC on neurotoxicity by MTT assay and to determine the LDH content in the supernatant. Results： Compared with those untreated with YZC, the rats having received YZC treatment got superiority in shorter time of platform seeking in Morris water maze test, as well as elongated latent period and less times of error in shuttle dark avoidance test. On the cultured neurons, YZC drug serum could effectively increase the survival rate of Aβ25-35 intoxicated neurons and reduce the LDH contents in cultured supernatant. Conclusion： YZC has an action of improving learning and memory disorder, and good protective effect on Aβ25-35 induced neurotoxicity in SD rats. KEY WORDS

Protective effect and its mechanism of codonopsis pilosula polysaccharide on memory consolidation disorder induced by cycloheximide in mice

OBJECTIVE To investigate the protective effect of Codonopsis Pilosula Polysaccharide(CPPS)on improving of the memory consolidation disorder induced by Cycloheximide and its possible mechanisms in mice.METHODS The mice was divided into five groups,as normal control group,cycloheximid model group,piracetam positive control group,CPPS 300 mg·kg^(-1) group,and CPPS150 mg·kg^(-1) group.The mice respectively were given saline,piracetam,and CPPS for 15 d.The memory consolidation disorder model in mice was established by ip.Cyclohexylamine,and orally administered CPPS(300 mg·kg^(-1) or 150 mg·kg^(-1))every day.Then experimental groups were subjected Morris Water Maze test.Western blotting analysis were used to analysis the expression of Ca MKⅡ/CREB signaling pathways.RESULTS Morris water maze experiment showed that cyclohexylamine can cause memory consolidation disorder(P<0.01),and giving piracetam and CPPS(300 mg·kg-1)can improve spatial memory impairment in mice(P<0.05,P<0.01).Western blotting experiment results show that compared with normal control group,Ca MKⅡand CREB contents of brain in model group mice had significant decreased(P<0.001);Compared with model group,Ca MKⅡand CREB contents of brain tissue in piracetam and CPPS groups increased significantly(P<0.05,P<0.01,P<0.001).CONCLUSION Cycloheximide can induce the memory consolidation disorder,and its effect in mice related to Ca MK/CREB signaling pathways.CPPS can improved this memory disorder by influence Ca MKⅡ/CREB signaling pathways.

Can outbred mice be used as a mouse model of mild cognitive impairment?

Deficits in spatial learning and memory are some of the earliest symptoms in mild cognitive impairment （MCI）. However, there are few valid MCI animal models available to evaluate putative therapeutic strategies. The aim of this study was to obtain a natural animal model of MCI. Outbred Kunming （aged 5 and 12.5 months） and ICR （7 and 12 months） mice were utilized in the present study. Morris water maze and radial six-arm water maze （RAWM） were simultaneously used to evaluate impaired spatial learning and memory in middle-aged mice （approximately 12 months of age）. Compared with younger mice in the respective groups, the middle-aged mice suffered visible impairment of spatial memory in the Morris water maze and RAWM, and mild spatial learning deficiency occurred in the RAWM study alone. Thus outbred Kunming and ICR mice could be utilized as a natural animal model for MCI, in particular for memory impairment studies.

Memory and behavior-related problems of patients with neurocognitive disorders and the attitudes of their caregivers

Objective:The purpose of this study was to investigate the memory and behavior-related problems of patients with neurocognitive disorders and the attitudes of their caregivers so as to provide an effective basis for nursing interventions against such problems.Methods:The subjects were selected from patients who were under treatment or short-term hospitalization between April 2011 and March 2012.One hundred fifty-three patients with neurocognitive disorders and their major caregivers were selected from 9 grade 3 Class A hospitals of Hunan Province.The Revised Memory and Behavior Problems Checklist(RMBPC)was used to measure the memory and behavior-related problems of patients with neurocognitive disorders and the influence on their caregivers.The occurrence of different memory and behavior-related prob-lems and the distress on their caregivers was compared.Results:The RMBPC investigation showed that among 153 patients and their caregivers,152(99.3%)had memory-related problems,137(89.5%)had depression,and 136 patients(88.9%)had destructive behaviors.The incidence of memory-related problems was higher than depression and destructive behaviors(P<0.01).Caregivers bore more distress when encountering destructive behaviors(1.95±1.13 points)than memory-related problems and depression(0.91±0.76 points and 0.89±0.85 points;P<0.01).Curve fitting was used to analyze the relationship between the number of memory and behavior-related problems and the distress on their caregivers.A curve correlation existed between the two factors(the recorded maximum value of the Cubic equation curve was 0.278,F=229.212,P<0.05).Conclusion:Among patients with neurocognitive disorders,memory-related problems had the highest incidence,while the caregivers bore the strongest distress when encountering destructive behaviors,thus interventions should be conducted in consideration of patient memory and behavior-related problems,and caregivers’attitude to further reduce caregiver burden.

Chronic caffeine exposure attenuates blast-induced memory deficit in mice

Objective： To investigate the effects of three different ways of chronic caffeine administration on blast- induced memory dysfunction and to explore the underlying mechanisms. Methods： Adult male C57BL/6 mice were used and randomly divided into five groups： control： without blast exposure, con-water： administrated with water continuously before and after blast-induced trau- matic brain injury （bTBI）, con-caffeine： administrated with caffeine continuously for 1 month before and after bTBI, pre-caffeine： chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI, post-caffeine： chronically administrated with caffeine after bTBI. After being subjected to moderate intensity of blast injury, mice were recorded for learning and memory performance using Morris water maze （MWM） paradigms at 1, 4, and 8 weeks post-blast injury. Neurological deficit scoring, glutamate concentration, proinflammatory cytokines production, and neuropathological changes at 24 h, 1, 4, and 8 weeks post-bTBl were examined to evaluate the brain injury in early and prolonged stages. Adenosine A1 receptor expression was detected using qPCR. Results： All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit, which is correlated with the neuroprotective effects against excitotoxicity, inflammation, astrogliosis and neuronal loss at different stages of injury. Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI; pre-bTBI and post-bTBI treatment of caffeine tended to exert neu- roprotective effects at early and prolonged stages of bTBI respectively. Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption. Conclusion： Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get, the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.

Effects of subconvulsive electrical stimulation to the hippocampus on emotionality and spatial learning and memory in rats

Objective To observe the effects of repeated subconvulsive electrical stimuli to the hippocampus on the emotional behavior and spatial learning and memory ability in rats.Methods One hundred and eight male Wistar rats were randomized into 3 groups. Animals in group SE (n = 42) were given subconvulsive electrical stimulation to the hippocampus through a constant pulsating current of 100 μA with an intratrain frequency of 25 Hz, pulse duration of 1 millisecond, train duration of 10 seconds and interstimulus interval of 7 minutes, 8 times a day, for 5 days. In the electrode control group or CE group (n = 33), animals were implanted with an electrode in the hippocampus, but were not stimulated. Group NC (n =33) animals received no electrode or any stimulation. The emotional behavior of experimental rats was examined by activity in an unfamiliar open field and resistance to capture from the open field, while the spatial learning and memory ability was measured during training in a Morris water maze.Results The stimulated rats tested 1 month after the last round of stimulation displayed substantial decreases in open field activity (scale: 10. 4±2. 3, P<0. 05) and increases in resistance to capture (scale: 2. 85±0. 56, P < 0. 01 ). The amount of time for rats in group SE to find the platform (latency) as a measurement for spatial bias was prolonged (29±7) seconds after 15 trials in the water maze, P<0. 05). The experimental rats swam aimlessly in all four pool quadrants during the probe trial in the Morris water maze.Conclusions Following repeated subconvulsive electrical stimuli to the hippocampus, rats displayed long-lasting significant abnormalities in emotional behavior, increased anxiety and defensiveness, enhanced ease to and delayed habituation to startlement, transitory spatial learning and memory disorder, which parallels many of the symptoms in posttraumatic stress disorder patients.

Effects of bisphenol A and bisphenol analogs on the nervous system

Estrogen impacts neural development;meanwhile, it has a protective effect on the brain. Bisphenols, primarily bisphenol A (BPA), can exert estrogen-like or estrogen-interfering effects by binding with estrogen receptors. Extensive studies have suggested that neurobehavioral problems, such as anxiety and depression, can be caused by exposure to BPA during neural development. Increasing attention has been paid to the effects on learning and memory of BPA exposure at different developmental stages and in adulthood. Further research is required to elucidate whether BPA increases the risk of neurodegenerative diseases and the underlying mechanisms, as well as to assess whether BPA analogs, such as bisphenol S and bisphenol F, influence the nervous system.

Intranasal administration of induced pluripotent stem cell-derived cortical neural stem cell-secretome as a treatment option for Alzheimer’s disease

Background Alzheimer’s disease(AD)is the most common neurodegenerative disorder in the elderly,resulting in gradual destruction of cognitive abilities.Research on the development of various AD treatments is underway;however,no definitive treatment has been developed yet.Herein,we present induced pluripotent stem cell(iPSC)-derived cortical neural stem cell secretome(CNSC-SE)as a new treatment candidate for AD and explore its efficacy.Methods We first assessed the effects of CNSC-SE treatment on neural maturation and electromagnetic signal during cortical nerve cell differentiation.Then to confirm the efficacy in vivo,CNSC-SE was administered to the 5×FAD mouse model through the nasal cavity(5μg/g,once a week,4 weeks).The cell-mediated effects on nerve recovery,amyloid beta(Aβ)plaque aggregation,microglial and astrocyte detection in the brain,and neuroinflammatory responses were investigated.Metabolomics analysis of iPSC-derived CNSC-SE revealed that it contained components that could exert neuro-protective effects or amplify cognitive restorative effects.Results Human iPSC-derived CNSC-SE increased neuronal proliferation and dendritic structure formation in vitro.Furthermore,CNSC-SE-treated iPSC-derived cortical neurons acquired electrical network activity and action potential bursts.The 5×FAD mice treated with CNSC-SE showed memory restoration and reduced Aβplaque accumulation.Conclusions Our findings suggest that the iPSC-derived CNSC-SE may serve as a potential,non-invasive therapeutic option for AD in reducing amyloid infiltration and restoring memory.

Clinical observation on effect of scalp electroacupuncture for mild cognitive impairment

OBJECTIVE: To evaluate the therapeutic effect of scalp electroacupuncture for mild cognitive impairment (MCI) in the early stage. METHODS: Two hundred and thirty three MCI patients were randomly divided into three groups: the drug group, the scalp electroacupuncture group, and the syndrome differentiation group. For the scalp electroacupuncture group, the points of Baihui (DU 20), Sishecong (EX-HN1), Fengchi (GB 20), and Shenting (DU 24) were selected. For the syndrome differentiation group, specific acupoints were added on the basis of syndrome differentiation and according to the scale for the differentiation of syndromes in vascular dementia (SDSVD) beside the acupoints used in the scalp electroacupuncture group. For the drug group, nimodipine was orally administered. Each patient was treated for two courses, eight weeks. The score differences in minimental state examination (MMSE), picture recognition, and clock drawing test were observed before and after the treatment. RESULTS: After treatment, the score differences in MMSE and clock drawing test were of obvious statistical significance among three groups (P<0.01, P<0.05). The score differences in picture recognition were of extremely statistical significance between the scalp electroacupuncture group and the syndrome differentiation group (P<0.01), while the difference was not found in the drug group (P>0.05). There were statistical significant differences in therapeutic effects between the scalp electroacupuncture group and the drug group, and between the syndrome differentiation group and the drug group (P<0.05), while no statistical difference was found between scalp electroacupuncture group and the syndrome differentiation group (P>0.05). CONCLUSION: All the three therapies may improve the cognitive function of MCI patients. The therapeutic effects in the scalp electroacupuncture and syndrome differentiation groups were basically the same, but superior to nimodipine.

Relationship between event-related potential P300 and first episode schizophrenia

Although P300 abnormalities of event-related .potentials （ERPs） are consistently reported among schizophrenic patients as being the most compelling indices of their brain dysfunction, whether they are trait markers or state markers of schizophrenia remains in controversy. To shed a light on this point, we made a longitudinal study of P300 among first episode schizophrenic patients, from no medication until the patients had been medicated for 12 weeks.

Clinical study on acupoint massage in improving cognitive function and sleep quality of elderly patients with hypertension

Objective：To investigate the effects of acupoint massage on cognitive function and sleep quality in elderly patients with hypertension. Methods：A total of 68 elderly patients with hypertension were enrolled, and their ages were all over 60 years old. They were divided into a control group and a treatment group by simple random method, with 34 cases in each group. Patients in the control group were treated by routine psychological health guidance and sleep knowledge education, while patients in the treatment group were treated by acupoint massage on the base of the interventions given to the control group. Both of their treatment courses were 3 months. Pittsburgh sleep quality index （PSQI） scores and mini-mental state examination （MMSE） scores before and after treatment were recorded and compared. Results：Two groups’ PSQI scores before treatment had no significant difference （P〉0.05）. After 3 months of treatment, their PSQI scores were statistically different （P〈0.05）. There was also no between-group statistical difference in MMSE score before treatment （P〉0.05）, but there was a significant difference after treatment （P〈0.05）. Conclusion：Acupoint massage for elderly patients with primary hypertension can improve their sleep quality and enhance their cognitive function, thus it is worthy of being applied in clinical nursing work.