Chronic colitis exacerbates NLRP3-dependent neuroinflammation and cognitive impairment in middle-aged brain.

BACKGROUND: Neuroinflammation is a major driver of age-related brain degeneration and concomitant functional impairment. In patients with Alzheimer's disease, the most common form of age-related dementia, factors that enhance neuroinflammation may exacerbate disease progression, in part by impairing the glymphatic system responsible for clearance of pathogenic beta-amyloid. Inflammatory bowel diseases (IBDs) induce neuroinflammation and exacerbate cognitive impairment in the elderly. The NACHT-LRR and pyrin (PYD) domain-containing protein 3 (NLRP3) inflammasome has been implicated in neuroinflammation. Therefore, we examined if the NLRP3 inflammasome contributes to glymphatic dysfunction and cognitive impairment in an aging mouse model of IBD. METHODS: Sixteen-month-old C57BL/6J and NLRP3 knockout (KO) mice received 1% wt/vol dextran sodium sulfate (DSS) in drinking water to model IBD. Colitis induction was confirmed by histopathology. Exploratory behavior was examined in the open field, associative memory by the novel-object recognition and Morris water maze tests, glymphatic clearance by in vivo two-photon imaging, and neuroinflammation by immunofluorescence and western blotting detection of inflammatory markers. RESULTS: Administration of DSS induced colitis, impaired spatial and recognition memory, activated microglia, and increased A1-like astrocyte numbers. In addition, DSS treatment impaired glymphatic clearance, aggravated amyloid plaque accumulation, and induced neuronal loss in the cortex and hippocampus. These neurodegenerative responses were associated with increased NLRP3 inflammasome expression and accumulation of gut-derived T lymphocytes along meningeal lymphatic vessels. Conversely, NLRP3 depletion protected against cognitive dysfunction, neuroinflammation, and neurological damage induced by DSS. CONCLUSIONS: Colitis can exacerbate age-related neuropathology, while suppression of NLRP3 inflammasome activity may protect against these deleterious effects of colitis.

Juvenile treatment with a novel mGluR2 agonist/mGluR3 antagonist compound, LY395756, reverses learning deficits and cognitive flexibility impairments in adults in a neurodevelopmental model of schizophrenia.

Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms. Therefore, treating cognitive deficits at an early stage is a realistic approach. In this study, we tested whether an early treatment targeting mGluR2 would be effective in ameliorating cognitive impairments in the methylazoxymethanol acetate (MAM) model of SCZ. We investigated the effects of an mGluR2 agonist/mGluR3 antagonist, LY395756 (LY39), on the NMDAR expression and function in juveniles, as well as cognitive deficits in adult rats after juvenile treatment. We found that gestational MAM exposure induced a significant decrease in total protein levels of the NMDAR subunit, NR2B, and a significant increase of pNR2BTyr1472 in the juvenile rat PFC. Treatment with LY39 in juvenile MAM-exposed rats effectively recovered the disrupted NMDAR expression. Furthermore, a subchronic LY39 treatment in juvenile MAM-exposed rats also alleviated the learning deficits and cognitive flexibility impairments when tested with a cross-maze based set-shifting task in adults. Therefore, our study demonstrates that targeting dysfunctional NMDARs with an mGluR2 agonist during the early stage of SCZ could be an effective strategy in preventing the development and progression in addition to ameliorating cognitive impairments of SCZ.

Physical exercise promotes recovery of neurological function after ischemic stroke in rats.

Although physical exercise is an effective strategy for treatment of ischemic stroke, the underlying protective mechanisms are still not well understood. It has been recently demonstrated that neural progenitor cells play a vital role in the recovery of neurological function (NF) through differentiation into mature neurons. In the current study, we observed that physical exercise significantly reduced the infarct size and improved damaged neural functional recovery after an ischemic stroke. Furthermore, we found that the treatment not only exhibited a significant increase in the number of neural progenitor cells and neurons but also decreased the apoptotic cells in the peri-infarct region, compared to a control in the absence of exercise. Importantly, the insulin-like growth factor-1 (IGF-1)/Akt signaling pathway was dramatically activated in the peri-infarct region of rats after physical exercise training. Therefore, our findings suggest that physical exercise directly influences the NF recovery process by increasing neural progenitor cell count via activation of the IGF-1/Akt signaling pathway.

Correct Information Unit Analysis in Different Discourse Tasks Among Persons With Anomic Aphasia Based on Mandarin AphasiaBank.

PURPOSE: This study aimed to explore how well persons with anomic aphasia communicate information during discourse regarding quantity, quality, and efficiency compared to neurotypical controls, to investigate the influence of discourse tasks on informativeness and efficiency and to examine impact factors like aphasia severity and cognitive ability. METHOD: Language samples of four discourse tasks from 31 persons with anomic aphasia and 31 neurotypical controls were collected from Mandarin AphasiaBank. Correct information unit (CIU) analysis measures including the total number of CIUs, percentage of CIUs, CIUs per minute, and words per minute were calculated. Group differences and the effects of discourse tasks on informativeness and efficiency were investigated. Correlations of CIU analysis measures with aphasia severity and cognitive ability were examined. RESULTS: Persons with anomic aphasia showed lower efficiency in conveying information than controls. They underperformed controls on all CIU analysis measures when executing story narrative tasks. Discourse tasks influenced the informativeness and efficiency of both groups. Neurotypical controls delivered the greatest quantity of information most efficiently when narrating stories. Persons with anomic aphasia exhibited reduced quantity of information during procedural discourse and displayed superior information quality in sequential-picture descriptions. Discourse information may be impacted by aphasia severity and cognitive ability, with varying effects depending on the task. CONCLUSIONS: Persons with anomic aphasia are inefficient in communicating discourse messages and perform poorly on all measures in story narratives. When measuring discourse information, the effects of discourse tasks and factors like aphasia severity and cognitive ability should be considered.

Discourse Task Type-Specific Linguistic Characteristics in Anomic Aphasia and Healthy Controls: Evidence From Mandarin-Chinese AphasiaBank.

PURPOSE: This study was designed to examine the hypothesis that discourse task types influence language performance in Mandarin Chinese-speaking people and to reveal the discourse task-specific linguistic properties of persons with anomic aphasia compared to neurotypical controls. METHOD: Language samples from persons with aphasia (n = 31) and age- and education-matched controls (n = 31) across four discourse tasks (sequential-picture description, single-picture description, story narrative, and procedural discourse) were collected from Mandarin AphasiaBank. Task-specific distributions of parts of speech were analyzed using mosaic plots. The main effects of tasks in each group and the between-group differences within each task for several typical linguistic variables were evaluated, including the mean length of utterance, tokens, moving-average type-token ratio, words per minute, propositional density, noun-verb ratio, noun percentage, and verb percentage. RESULTS: The results revealed an impact of discourse tasks on most language variables in both groups. In the healthy controls, story narratives yielded the highest total words and lowest verb percentage. In the aphasia group, procedural discourse elicited the fewest total words and densest expressions, whereas their single-picture descriptions had the highest noun-verb ratio. For all tasks, the aphasia group performed worse than the control group in the mean length of utterance, tokens, moving-average type-token ratio, and words per minute. For noun-verb ratio, noun percentage, and verb percentage, only one task (i.e., single-picture description) showed significant between-group differences. CONCLUSION: The selection of discourse tasks should be addressed in assessments and interventions for Mandarin Chinese-speaking individuals with aphasia to obtain more accurate and feasible outcomes.

[Clinical effect of ultrasound combined with anatomy-measure guidance botulinum toxin type A injection in poststroke patients with spasticity].

OBJECTIVE: To evaluate the clinical efficacies of botulinum toxin type A (BTX-A) injection under ultrasonic guidance and body surface positioning in poststroke patients with lower extremities spasticity. METHODS: From January 2009 to January 2011, a total of 18 patients with stroke-related spasticity in lower extremities were recruited at Third Affiliated Hospital of Sun Yat-sen University. Under the guide of color Doppler ultrasound and body surface positioning, BTX-A was injected into multi-points of muscles. The outcome after BTX-A injection was assessed by modified Ashworth scale (MAS), passive range of movement (PROM), 10-meter walking test (10 MWT) and Berg balance scale (BBS). Assessments were performed at baseline, Day 3, Weeks 1, 2, 4 and 12 post-injection respectively. RESULTS: Compared the scores of MAS (MAS(pre-treatment) 2.6 ± 0.5, MAS(post-treatment) 1.9 ± 0.2 - 1.1 ± 0.3 score), PROM (PROM(pre-treatment) 7.2 ± 2.4°, PROM(post-treatment) 12.3 ± 2.0 - 18.6 ± 2.2°) between baseline and follow-up at Weeks 1, 2, 4 and 12 post-treatment, there were significant statistical differences (P < 0.05).10 MW (10 MWT(pre-treatment) 55.1 ± 5.2 s, 10 MWT(post-treatment) 48.6 ± 4.2 - 42.9 ± 3.8 s) and BBS (BBS(pre-treatment) 34.7 ± 5.1, BBS(post-treatment) 39.9 ± 4.9 - 45.8 ± 2.1 score) improved greatly at Weeks 2, 4 and 12 post-treatment. CONCLUSION: Ultrasonic guidance and body surface positioning is an accurate positioning modality of using BTX-A for treating the spasticity of lower extremities.

[Effects of exercise training on synaptic plasticity in rats with focal cerebral infarction].

OBJECTIVE: To examine the roles of exercise training in the improvement of damaged neural function and synaptic plasticity. METHODS: An infarction model was induced by left middle cerebral artery occlusion (MCAO). A total of 70 adult Sprague-Dawley rats were randomly divided into 3 groups: physical exercise group (n = 30) undergoing running wheel exercise daily after MCAO, control group (n = 30) and sham-operated group (n = 10). The latter two groups were fed in standard cages without any special training exercise. The rats were scarified at Days 3, 7, 14, 21 and 35 for the evaluation of neural function by neurological severity scores (NSS). And the synaptic ultrastructures at peri-infarction region were examined by specific marker synaptophysin (SYN). RESULTS: Synaptic ultrastructures at peri-infarction region were observed in both the control and exercise training groups. The presynaptic and postsynaptic membranes were relatively intact. And the presynaptic membranes had more synaptic vesicles from Day 7 post-ischemia. The number of SYN positive cells significantly increased in the exercise training group (21 d: 0.8 ± 0.1; 35 d: 0.7 ± 0.1) versus those in the control group (21 d: 0.4 ± 0.1; 35 d: 0.5 ± 0.1) at Days 21 and 35 post-ischemia (P < 0.05). Moreover, the neurological severity scores in the exercise training group (7 d: 7.8 ± 0.8; 14 d: 5.6 ± 0.8; 21 d: 3.3 ± 0.8; 35 d: 3.0 ± 0.8) showed a quicker declination versus those in the control group (7 d: 8.8 ± 0.7; 14 d: 7.7 ± 0.9; 21 d: 6.9 ± 0.8; 35 d: 4.2 ± 0.8) from Day 7 post-ischemia (P < 0.05). CONCLUSION: Exercise training plays an important role in the recovery of damaged neural function and synaptic plasticity after cerebral infarction in rats.

Ultrasound Stimulation of Prefrontal Cortex Improves Lipopolysaccharide-Induced Depressive-Like Behaviors in Mice.

Increasing evidence indicates that inflammatory responses may influence brain neurochemical pathways, inducing depressive-like behaviors. Ultrasound stimulation (US) is a promising non-invasive treatment for neuropsychiatric diseases. We investigated whether US can suppress inflammation and improve depressive-like behaviors. Mice were intraperitoneally injected with lipopolysaccharide to induce depressive-like behaviors. Ultrasound wave was delivered into the prefrontal cortex (PFC) for 30 min. Depressive- and anxiety-like behaviors were evaluated through the forced swimming test (FST), tail suspension test (TST), and elevated plus maze (EPM). Biochemical analyses were performed to assess the expression of inflammatory cytokines in the PFC and serum. The results indicated that US of the PFC significantly improved depressive-like behaviors in the TST (p < 0.05) and FST (p < 0.05). Anxiety-like behaviors also improved in the EPM (p < 0.05). Furthermore, the lipopolysaccharide-mediated upregulation of IL-6, IL-1ß, and TNF-α in the PFC was significantly reduced (p < 0.05) by US. In addition, no tissue damage was observed. Overall, US of PFC can effectively improve lipopolysaccharide-induced depressive-like behaviors, possibly through the downregulation of inflammatory cytokines in the PFC. US may be a safe and promising tool for improvement of depression.

[Study of lower extremity muscle function in stroke patients by velocity-encoded phase-contrast magnetic resonance imaging].

OBJECTIVE: To compare the difference of muscle dynamic characteristics for the ankle dorsiflexors and plantarflexors between stroke patients at the chronic stage and healthy controls so as to provide a new method of assessing the in vivo muscle function in patients with hemiplegia. METHODS: From May 2008 to May 2009, 26 stroke patients and 21 age-and gender-matched normal controls were recruited. All subjects were positioned on a scanner table and requested to perform the voluntary movement of ankle flexion-extension. The velocity encoded phase contrast magnetic resonance imaging (VE-PC MRI) provided the images of tibialis anterior muscle (TA), medial head of gastrocnemius muscle (MG) and soleus muscle (SOL) during a movement cycle. By measuring the calf muscle contraction velocity, the balance function was assessed by Berg balance scale (BBS). The correlation between scores of BBS and the mean maximum velocity were compared and analyzed. RESULTS: The peak velocity of TA (1 - 8 phase, 8.900 - 21.120 mm/s vs 12.99 - 34.50 mm/s), MG (12-19phase, 13.60 - 13.28 mm/s vs 25.85 - 18.38 mm/s) and SOL (12 - 16 phase, 18.63 - 33.62 mm/s vs 27.68 - 47.22 mm/s) was lower in the affected side than that in the controls during ankle extension (P < 0.05); During ankle dorsiflexion, the co-contraction index of SOL/TA (2 - 9 phase, 0.81 - 0.82 vs 0.27 - 0.44) and the co-contraction index of GM/TA (2 - 9 phase, 0.73 - 0.58 vs 0.10 - 0.11) was markedly higher in the affected side than the controls. The patient score of BBS was negatively correlated with the mean velocity of TA (r = -0.69, P = 0.001) and GM (r = -0.47, P = 0.01) in the affected side. There was correlation between TA (r = -0.60, P = 0.001) and GM (r = -0.49, P = 0.01) in the unaffected side. CONCLUSION: During the movement of active ankle flexion-extension, the velocities of TA, SOL and MG are lower in the affected side. The co-contraction index is markedly higher in the affected side during ankle dorsiflexion. This in turn leads to a decline of balance function in patients. VE-PC MRI can provide quantitative in vivo measurements of lower extremity muscle function in stroke patients.

Explore combined use of transcranial direct current stimulation and cognitive training on executive function after stroke.

OBJECTIVE: To explore the effects of transcranial direct current stimulation combined with cognitive training on executive function and activities of daily living performance among stroke patients. METHODS: A total of 50 subjects were enrolled and randomly allocated into 2 groups of 25 each. The real-transcranial direct current stimulation group was simultaneously subjected to transcranial direct current stimulation and cognitive training, while the sham-transcranial direct current stimulation group was simultaneously subjected to sham transcranial direct current stimulation and cognitive training. At baseline, and after treatment, each subject was assessed with the Wisconsin Card Sorting Test (WCST), Stroop Color-Word Test (SCWT), Digital Symbol Test (DST), Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Activities of Daily Living Scale (ADLs). RESULTS: After treatment, the gains in most indices of WCST, SCWT, DST, MMSE, MoCA and ADLs in the real-transcranial direct current stimulation group were significantly higher than those in the sham-transcranial direct current stimulation group (p<0.05). Nonetheless, no significant differences were noted in the gains in SCWT (including only Part A time and error, and Part B time) and activities of daily living (including only basic activities of daily living) between the 2 groups (p>>0.05). CONCLUSION: Transcranial direct current stimulation combined with cognitive training was found to significantly enhance executive function and instrumental activities of daily living performance among stroke patients.

[Relationship between the changes of surface electromyographic signal of thigh muscle and balance function in stroke patients].

OBJECTIVE: To explore the relationship between the changes of surface electromyography (sEMG) signal of thigh muscles and balance function in stroke patients during maximum isometric voluntary contraction (MIVC) of knee extension and flexion so as to provide rationales for rehabilitation. METHODS: Twenty-one stroke patients and 18 age- and sex-matched normal controls were recruited for this study. The surface electromyographic signals of of vastus medialis (VM), rectus femoris (RF), vastus lateralis (RL) and biceps femoris (BF) were recorded during MIVC of knee extension and flexion. Root mean square (RMS) and co-contraction ratio (CR) of both groups were compared and analyzed. The balance function was assessed by Berg balance scale (BBS). RESULTS: There were significant differences in RMS of VM, RF, VL and BF of ipsilateral [(136 +/- 63) microV, (107 +/- 24) microV, (154 +/- 19) microV, (91 +/- 63) microV], thigh during knee extension and flexion (P < 0.05). There were significant differences in CR on ipsilateral thigh muscles than the unaffected (43% +/- 13% vs 37% +/- 20%) and controls (43% +/- 13% vs 32% +/- 10%) during knee flexion (P < 0.05). The RMS of RF and BF on ipsilateral thigh was significantly positively correlated with the score of BBS (rRF = 0.53, P = 0.01 vs rBF = 0.51, P = 0.02); The CR of knee extension and flexion on ipsilateral thigh had a significantly negative correlation (CRE = -0.59, P = 0.005 vs. CRF = -0.41, P = 0.046). CONCLUSION: The strength of bilateral thigh muscles decreases in stroke patients. The spasticity of thigh extensor still exists. Besides reducing the spasticity of hemiplegic limb extensor, rehabilitation should also focus upon bilateral thigh muscles, particularly ipsilateral RF and BF strength training to improve the knee joint stability and improve the balance function.

Overexpression of Slit2 decreases neuronal excitotoxicity, accelerates glymphatic clearance, and improves cognition in a multiple microinfarcts model.

BACKGROUND: Cerebral microinfarcts (MIs) lead to progressive cognitive impairments in the elderly, and there is currently no effective preventative strategy due to uncertainty about the underlying pathogenic mechanisms. One possibility is the dysfunction of GABAergic transmission and ensuing excitotoxicity. Dysfunction of GABAergic transmission induces excitotoxicity, which contributes to stroke pathology, but the mechanism has kept unknown. The secreted leucine-rich repeat (LRR) family protein slit homologue 2 (Slit2) upregulates GABAergic activity and protects against global cerebral ischemia, but the neuroprotective efficacy of Slit2 against MIs has not been examined. METHODS: Middle-aged Wild type (WT) and Slit2-Tg mice were divided into sham and MI treatment groups. MIs were induced in parietal cortex by laser-evoked arteriole occlusion. Spatial memory was then compared between sham and MI groups using the Morris water maze (MWM) task. In addition, neuronal activity, blood brain barrier (BBB) permeability, and glymphatic clearance in peri-infarct areas were compared using two-photon imaging, while GABAergic transmission, microglial activation, neuronal loss, and altered cortical connectivity were compared by immunofluorescent staining or western blotting. RESULTS: Microinfarcts increased the amplitude and frequency of spontaneous intracellular Ca2+ signals, reduced neuronal survival and connectivity within parietal cortex, decreased the number of GABAergic interneurons and expression of vesicular GABA transporter (VGAT), induced neuroinflammation, and impaired both glymphatic clearance and spatial memory. Alternatively, Slit2 overexpression attenuated dysfunctional neuronal Ca2+ signaling, protected against neuronal death in the peri-infarct area as well as loss of parietal cortex connectivity, increased GABAergic interneuron number and VGAT expression, attenuated neuroinflammation, and improved both glymphatic clearance and spatial memory. CONCLUSION: Our results strongly suggest that overexpression of Slit2 protected against the dysfunction in MIs, which is a potential therapeutic target for cognition impairment in the elderly.

C-C chemokine receptor type 2-overexpressing exosomes alleviated experimental post-stroke cognitive impairment by enhancing microglia/macrophage M2 polarization.

BACKGROUND: Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke. The activity of exosomes has been verified to be comparable to the therapeutic effects of mesenchymal stromal cells. However, the effects of exosomes derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) (ExoCtrl) on post-stroke cognitive impairment (PSCI) have rarely been reported. Moreover, whether exosomes derived from C-C chemokine receptor type 2 (CCR2)-overexpressing HUC-MSCs (ExoCCR2) can enhance the therapeutic effects on PSCI and the possible underlying mechanisms have not been studied. AIM: To investigate the effects of ExoCtrl on PSCI and whether ExoCCR2 can enhance therapeutic effects on PSCI. METHODS: Transmission electron microscopy, qNano® particles analyzer, and Western blotting were employed to determine the morphology and CCR2 expression of ExoCtrl or ExoCCR2. ELISA was used to study the binding capacity of exosomes to CC chemokine ligand 2 (CCL2) in vivo. After the intravenous injection of ExoCtrl or ExoCCR2 into experimental rats, the effect of ExoCtrl and ExoCCR2 on PSCI was assessed by Morris water maze. Remyelination and oligodendrogenesis were analyzed by Western blotting and immunofluorescence microscopy. QRT-PCR and immunofluorescence microscopy were conducted to compare the microglia/macrophage polarization. The infiltration and activation of hematogenous macrophages were analyzed by Western blotting and transwell migration analysis. RESULTS: CCR2-overexpressing HUC-MSCs loaded the CCR2 receptor into their exosomes. The morphology and diameter distribution between ExoCtrl and ExoCCR2 showed no significant difference. ExoCCR2 bound significantly to CCL2 but ExoCtrl showed little CCL2 binding. Although both ExoCCR2 and ExoCtrl showed beneficial effects on PSCI, oligodendrogenesis, remyelination, and microglia/macrophage polarization, ExoCCR2 exhibited a significantly superior beneficial effect. We also found that ExoCCR2 could suppress the CCL2-induced macrophage migration and activation in vivo and in vitro, compared with ExoCtrl treated group. CONCLUSION: CCR2 over-expression enhanced the therapeutic effects of exosomes on the experimental PSCI by promoting M2 microglia/macrophage polarization, enhancing oligodendrogenesis and remyelination. These therapeutic effects are likely through suppressing the CCL2-induced hematogenous macrophage migration and activation.

NLRP3-dependent microglial training impaired the clearance of amyloid-beta and aggravated the cognitive decline in Alzheimer's disease.

Alzheimer's disease (AD), the most common form of dementia, is marked by progressive cognitive decline, deposition of misfolded amyloid-ß (Aß) peptide and formation of neurofibrillary tangles. Recently, microglial training has emerged as an important contributor to neurological diseases, which augments the subsequent inflammation. However, how it affects the pathology of AD remains unknown. Here, using a mouse model of sporadic Alzheimer's disease (SAD) induced by streptozotocin injection, we demonstrated that microglial training exacerbated Aß accumulation, neuronal loss, and cognitive impairment. In addition, we injected MCC950 to inhibit NLRP3 activation and used an inducible Cre recombinase to delete the NLRP3 gene in microglia. Inhibition or depletion of microglial NLRP3 could protect against the pathologies of SAD and abolish the effects of microglial training. Our results identified microglial training as an important modifier of neuropathology in SAD and demonstrated that activation of NLRP3 inflammasome contributed to the pathologies and microglial training in SAD. Therefore, NLRP3 could be a potential therapeutic target for SAD treatment.

[Analysis of influence factors of cognitive impairment following first onset of stroke].

OBJECTIVE: To explore the influence factors of cognitive impairment following first onset of stroke, in order to predict the existence of cognitive impairment in patients with stroke and help for future clinical intervene. METHODS: 364 survivors of first onset of stroke were evaluated by the mini-mental state examination (MMSE) in this study. Data were collected on age, gender, education level, location of brain lesion, diagnostic stroke subtype and so on. Logistic regressions analyzing is used to determine those factors that could predict cognitive impairment of stroke patients by MMSE assessment score. RESULTS: The factors including location of brain lesion, area of the lesion, high homocysteine, side of the lesion, complications, education level and age can join in the logistic regression analysis format. The R of the format is 0.849 and these seven factors can explain 72.1% variation of the scores of MMSE. CONCLUSION: The logistic regression analysis revealed that location of brain lesion, area of the lesion, high homocysteine, side of the lesion, complications, education level and age were predictors of the cognition function assessment of stroke patients. The prevalence of cognitive impairment can be mainly influenced by these factors.

Diffusion tensor imaging of the brain in patients with Alzheimer's disease and cerebrovascular lesions.

BACKGROUND: Recent autopsy study showed a high incidence of cerebrovascular lesions in Alzheimer's disease (AD). To assess the impact of cerebrovascular pathology in AD, we used diffusion tensor imaging (DTI) to study AD patients with and without cerebrovascular lesions. MATERIALS AND METHODS: Conventional and DTI scans were obtained from 10 patients with probable AD, 10 AD/V patients (probable AD with cerebrovascular lesions) and ten normal controls. Mean diffusivity (D) and fractional anisotropy (FA) values of some structures involved with AD pathology were measured. RESULTS: D value was higher in AD patients than in controls in hippocampus and the cingulate gyrus. In AD/V patients, increased D value was found in the same structures and also in the thalamus and basal ganglia compared to controls. There was a significant difference of D value between AD and AD/V patients. FA value reduced in the white matter of left inferior temporal gyrus and in the bilateral middle cingulate gyrus in patients with AD/V compared with controls. The MMSE (mini-mental state examination) score significantly correlated with FA value in the right hippocampus (r=0.639, P<0.019), in the right anterior cingulate gyrus (r=0.587, P<0.035) and in left parahippocampal gyrus (r=0.559, P<0.047). CONCLUSION: Cerebrovascular pathology had stronger impact on the D value than the AD pathology alone did. Elevated D value in thalamic and basal ganglia may contribute to cognitive decline in AD/V patients. Reduced FA values in AD/V patients may indicate that cerebrovascular pathology induced more severe white matter damage than the AD pathology alone did.

[Analysis of influence factors of post-stroke depression].

OBJECTIVE: To explore the influence factors of post-stroke depression by using Hamilton's depression scale (HAMD). METHODS: One hundred and eighty stroke survivors were involved in this study. Data were collected on age, sex, education, location of brain lesion, diagnostic stroke subtype and so on. We used multiple regressions analyzing to determine those factors that could predict Hamilton's depression scale (HAMD) scores of stroke patients. RESULTS: The multiple regression analysis of mean scores revealed that whether receiving rehabilitation therapy or not, personality, supports of family, age, complications and economical status were predictors of the result of the patient's global post-stroke depression assessment. CONCLUSION: The results of the present study call for more individually tailored. The prevalence of post-stroke depression can be influenced by multifaceted rehabilitative approaches including rehabilitation therapy, personality, supports of family, age, controlling complications and economical status.

Perspectives on the mGluR2/3 agonists as a therapeutic target for schizophrenia: Still promising or a dead end?

Group II metabotropic glutamate receptor (mGluR2/3) agonists once showed promise as non-dopaminergic antipsychotic drugs because of their efficacy in alleviating symptoms of schizophrenia (SZ) in both animal models and human patients. However, the recent failure of Phase III clinical trials dealt a huge blow to the scientific community and the aftershock of the setback in mGluR2/3 research can be felt everywhere from grant support and laboratory studies to paper publication. An immediate question raised is whether mGluR2/3 is still a promising therapeutic target for schizophrenia. Answering this question is not easy, but apparently a new strategy is needed. This article provides a focused review of literature on the study of mGluR2/3 agonists, especially on mGluR2/3 agonists' mechanism of action and efficacy in both normal conditions and animal models of SZ, as well as clinical studies in human patients with the disease. We argue that the cellular and molecular actions of mGluR2/3 agonists, the distinct roles between mGluR2 and mGluR3, as well as their effects on different stages of the disease and different subpopulations of patients, remain incompletely studied. Until the mechanisms associated with mGluR2/3 are clearly elucidated and all treatment options are tested, it would be a great mistake to terminate the study of mGluR2/3 as a therapeutic target for schizophrenia. This review will thus shed light on the comprehensive features of the translational potential mGluR2/3 agonists as well as the need for further research into the more selective activation of mGluR2.