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Stroke is one of the most important diseases in the world with high mortality and disability rate. Acute ischemic stroke (AIS) is more than 80% in total. At present, the main treatments for AIS include intravenous thrombolysis and endovascular mechanical thrombectomy. Cognitive impairment is a common or potentially disabling effect of stroke, but the optimal treatment of post-stroke cognitive impairment remains controversial. This article reviews the effects of treatments for acute ischemic stroke on cognitive function.
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Objective To investigate the effects of low dose of gamma knife irradiation on the expression of N-methyl-D-aspartate (NMDA) receptor subunits in cortex and hippocampus of epileptic rats. Methods The rats were randomly divided into 4 groups: control group, GK group, pentylenetetrazole (PTZ) group and GK+ PTZ group. The rats were injected intraperitoneally with PTZ to establish the epileptic models. Gamma knife irradiation was performed on bilateral frontal cortex of rats at a peripheral dose of 15Gy. After irradiation, the changes of the seizure and behaviors were observed and recorded. The rats were killed on the 12th week after irradiation, Immunohistochemstry and western blotting were used to detect the relative expression levels of NMDAR subunits (NR1, NR2A, and NR2B) in the cortex and hippocampus. Results There were no epileptic seizures in the control group and the GK group. Compared with the PTZ group, the epileptic seizures of rats in the GK+PTZ group were significantly reduced after low dose gamma knife irradiation (P<0.05). Compared with control group, the protein expression levels of NR1, NR2A and NR2B in the PTZ group increased significantly in the cortex and hippocampus, and so were the positive neurons and their average absorbance value (P<0.05). Compared with PTZ group, the protein expression levels of NR1, NR2A and NR2B of the GK+PTZ group decreased remarkably in the cortex and hippocampus (P<0.05). Protein expression levels of NR1, NR2A and NR2B were not significantly different between control group and GK group (P>0.05). Conclusion Epileptic rats exhibited an increase in the protein expression levels of NR1, NR2A and NR2B in the cortex and hippocampus while low dose of gamma knife irradiation can decrease expression levels of NMDA receptor subunits in the cortex and hippocampus of epileptic rats, which might represent a possible mechanism underlying the therapeutic effects of gamma knife irradiation on epileptic seizure.
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Objective To investigate the lesionsin theleft thalamus and to explore their correlation with executive functionin patients with subcortical ischemic vascular disease(SIVD)by using 1H magnetic resonance spectroscopy (1H-MRS) and diffusion tensor imaging (DTI). Methods Fourteen patients with vascular dementia (VaD), 14 patients with vas-cular cognitive impairment without dementia(VCIND)and 14 normal controls (NC) were recruited. The quantitative analy-sis of N-acetylaspartate (NAA), Choline (Cho), myoinositol (MI) and Creatine (Cr) resonance signals in region of interests (ROI) in the left thalamus were measured. Fractional anisotropy (FA) and mean diffusivity (MD) values in the same region were examined by using DTI. The relationship were analyzedamong the MRS, DTI ratios and cognitive impairment reflect-ed in MMSE and trail making test(TMT). Results The NAA/Cr ratio showed a gradual decrease in the left thalamus of VaD andVCIND patients compared with controls(F=3.656, P=0.038). There was no significant difference in NAA/Cr ra- tiobetween VaD and VCIND patients.Compared with controls, patients with VaD and VCIND demonstrated increased MD value in the left thalamus(F=3.882, P=0.030).There was no significant difference in MD value between VaD and VCIND patients (P>0.05). There were no correlations between NAA/Cr, MI/Cr, Cho/Cr value and DTI parameters in the ROI (P>0.05). TMTb time was positively associated with Cho/Cr(r=0.520,P=0.001 ) and with MD value in the left thalamus (r=0.305, P=0.044). Conclusions Combination of 1H-MRS with DTI can provide the valuable informationon the potential lesions in the thalamus in patients with SIVD. The Cho/Cr and MD values in the leftthalamus may be correlated with ex-ecutive function.
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Vascular cognitive impairment refers to the learning and memory impairments caused by cerebrovascular lesions.Studies in recent years have shown that oxidative stress plays an important role in vascular cognitive impairment.This article reviews the mechanisms and the prevention and treatment of oxidative stress in vascular cognitive impairment.
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Objective To investigate the expressions of protein kinase B (PKB/Akt) and glycogen synthase kinasc-3β in the hippocampus in mice with vascular dementia (VaD) induced by repetitive bilateral common carotid artery occlusion.Methods Forty-eight healthy adult male C57B1/6 mice were randomly allocated into 3 group:normal group,sham operation group,and model group (n =16 in each group).A mouse VaD model was induced by intermittent blocking the bilateral common carotid artery for 3 times in the model group.The sham group only separated the bilateral common carotid artery,but did not block it.The normal group did not receive any treatment.The behavioral changes of the mice were observed using the water maze and step-down tests at 4 weeks after procedure.HE staining was used to observe the histopathological changes of hippocampal tissue.The Western blotting was used to detect the expressions of Akt,p-Akt (Ser473),GSK3β and p-GSK3β (Ser9) proteins.Results In the water maze test,the time of swimming the entire distance was prolonged at the learning stage and memory stage (learning stage:F =19.389,P <0.05; memory stage:F =27.929,P < 0.05),the number of errors increased (learning stage:F =7.228,P < 0.05; memory stage:F =21.189,P<0.05) in the model group.In the step-down test,the response time was prolonged (F=19.162,P <0.05) at learning stage and the number of errors increased (F =6.562,P < 0.05),the latency time was shortened (F=10.634,P<0.05) and the number of errors increased (F=12.890,P<0.05) in the model group.At the same time,HE staining showed the reduction of neurons and the proliferation of glial cells in the hippocampal CA1 region in the model group; p-Akt (Ser473) (F=37.849,P<0.05) and p-GSK3β (Ser9)(F =67.725,P <0.05) protein expressions were up-regulated significantly (F =37.849,P <0.05; F =67.725,P<0.05) at 4 weeks after procedure compared to those in the sham operation group,while there were no significant differences in Akt (F =1.004,P >0.05) and GSK3β(F =0.329,P >0.05) total protein expressions among all groups.Conclusions The repetitive bilateral common carotid artery occlusion may result in learning and memory impairment and severe damage in the hippocampus in mice.The Akt and GSK3β expressions may be involved in the mechanism of VaD.
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Vascular cognitive impaiment (VCI) refers to a large class of clinical syndromes caused by vascular risk factors,obvious or not obvious cerebrovascular diseases from mild cognitive impairment to dementia.Looking for a physiologically controllable and repeatable animal model is critical for the systematic research of the VCI pathophysiological processes and the evaluation of new treatment methods.
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Vascular cognitive impairment (VCI) is a large class syndrome caused by a variety of cerebrovascular diseases from mild cognitive impairment to dementia.In the VCI animal experiments,choosing a reliable test method is particularly important for evaluating animal cognitive function and the improving the quality of animal models.
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Ischemic cerebrovascular disease results in electrophysiological changes of the cerebral cortex.Magnetoencephalography (MEG) can objectively and sensitively detect cortical magnetic field.It has a very high temporal and spatial resolution,and locates the magnetic field source.At present,MEG is mainly used for the detection of spontaneous wave and the detection of somatosensory evoked magnetic fields,auditory evoked magnetic fields,visual evoked magnetic fields,and event-related magnetic fields,and provides valuable information for cortex function changes of ischemic cerebrovascular disease.However,further study is still needed.
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Subcortical ischemic vascular disease (SIVD) is one of the most common subtypes in vascular cognitive impairment.This article reviews the research progress in the aspects of its pathogenesis,neuropsychological performance,imaging changes,and biological markers of SIVD.
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Objective To explore the correlation between executive function and white matter lesions (WML) and the diagnostic value by clock drawing test(CDT) in patients with vascular dementia (VaD). Methods Twenty-seven VaD patients and twenty-five normal control subjects were evaluated with CDT to assess the executive function. CDT was scored according the four point method. Age-related white matter change rating scale (ARWMCrs) was used qualitatively to measure and locate the WML by cranial MRI scanning. Results 1. The scores of CDT in normal cognition health and VaD were ( 3.88 ± 0. 33 ) and ( 1.74 ± 0. 98 ). The difference between two groups was statistically significant (P<0. 01 ). The humerous part and the point part were the earliest to decline in the VaD Patients. The scores of WML were (5.12 ± 4. 19) and ( 11.19± 3.09), respectively. There was significant difference between two groups(P < 0. 01 ). The scores of CDT had significant positive correlation with MMSE scores and negative correlation with WML scores (P < 0. 01 ). Conclusion The executive functional impairment in patients with VaD could be associated with the degree of WML.
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Objective To test amyloid beta protein(Aβ)40 and Aβ42 levels in CSF and apolipoprotein E (ApoE) genotype in patients with Alzheimer's disease(AD) and study whether or not the Aβ is related to the severity of dementia and the genotypes of ApoE.Methods 48 AD patients including 27 cases of mild type and 21 cases of serious type and 35 normal controls were selected.Aβ40 and Aβ42 in CSF and ApoE genotype were analyzed.Results Aβ40 levels were ( 12.3 ±4.6) μg/L,( 11.7 ±4.1 ) μg/L,( 12.6 ±4.9) μg/L and ( 11.0 ±3.7) μg/L(t = 1.377,0.705 and 1.385 ,all the p values were greater than 0.05) and Aβ42 levels were ( 105.3 ±25.4) ng/L,(110.7 ±21.7) ng/L,(96.9 ±23.9) ng/L and (123.5 ±29.6) ng/L(t=3.006,2.832,and 3.488,all the p values less than 0.01 ),in AD group,mild AD group,moderate to serious AD group and normal controls,respectively.Aβ40 levels were (11.9 ± 5.2) μg/L vs.(10.5 ± 3.8) μg/L in AD and controls with ApoEε4(t=0.696,P>0.05) and (12.6 ±4.5) μg/L vs.(11.4 ±3.4) μg/L without ApoEε4(t = 1.008,P>0.05).Aβ42 levels were (99.7 ± 23.8) ng/L vs.( 129.6 ± 31.0) ng/L in AD and controls with ApoEε4( t =1.632,P > 0.05 ) and ( 110.4 ± 28.4) ng/L vs.( 129.6 ± 31.0) ng/L in those without ApoEε4 ( t = 2.110,P <0.05 ).Conclusions The CSF level of Aβ is abnormal in AD,and it is related to the severity of the disease and the ApoE genotypes.
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Objective To investigate the pattern of the cerebral white matter lesions in patients with mild and moderate Alzheimer's disease(AD)and healthy controls using proton magnetic resonance spectroscopy(~1H-MRS)and diffusion tensor imaging(DTI).Methods Twenty AD patients and Twenty healthy controls were recrnited.All subjects underwent clinical examination,neuropsychological assessment.The quantitative analysis of N-acetylaspartate(NAA),myoinositol(mI),Chotine(Cho)and Creatine(Cr)resonance signals in region of interests(ROIs)located in the paraventricular white matter region bilaterally were measured.Ratios of NAA/Cr,mI/Cr and Cho/Cr were calculated in two groups.In addition,conventional MRI and DTI scanning were received,fractional anisotropy(FA)and mean diffusivity(MD)values of white matter in the same regions were measured respectively.Results No significant difference between two groups were observed in NAA/Cr ratio(P>0.05).A significantly increased mI/Cr and Cho/Cr were found in AD patients than in controls(P<0.05).FA and MD values in AD patients were 0.470±0.082 and 0.771±0.099,and in controls were 0.539±0.068 and 0.691±0.064,respectively.FA value decreased significantly in AD patients(P<0.05),M D value increased significantly in AD patients(P<0.05).After controlling for age-related,partial correlation analysis revealed a negtive correlation between mI/Cr and FA value in the patients with AD(P<0.05).No correlation between mI/Cr and MD was found(P>0.05).Conclusion The results suggest that not only the gray matter is injured,but also the white matter is abnormal in AD patients.Combining ~1H-MRS with DTI alterations could provide the valuable informations about white matter lesions in AD patients.
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Objective To investigate the relationship of lacunar infarction (LI) and white matter lesion with cognitive impairment in patients with subcortical ischemic vascular disease (SIVD) Methods Fifty-three patients were diagnosed as SIVD according to the criteria of Erkinjuntti. The symptoms and signs were recorded by an interview and examination, and neuropsychological assessment and magnetic resonance imaging (MRI) were performed. A semi-automated MRI quantitative method was used to measure the volume of white matter hyperintensity (WMH) and the number of LI was counted. Correlation and the partial correlation analysis were performed to examine the relationship of general cognitive function with the volume of WMH and the number of LI. Results The pseudobulbar paralysis symptom and the upper motoneuron injury sign were the most common in these patients (18.9% and 37.7%). Correlation analysis showed that there was positive correlation between the volume of WMH and age (r = 0. 518, P < 0. 05), and there was negative correlcction between mini-metal state examination (MMSE) scures and the volume of WMH (r=-0.514, P<0. 05), After controlling confounding factors, only age was positively correlated with the volume of WMH (r=0. 400, P=0. 004). There were negative correlation between the number of LI, the volume of WMH and MMSE scores(r=-0. 456,-0. 514,-0. 385,-0. 382;all P<0. 05), and the years of education was positively correlated with MMSE scores (r= 0. 518, P< 0. 001). Conclusions Age may not be the main risk factor for cognitive impairment in patients with SIVD. The volume of WMH and the number of LI are independent risk factors for cognitive impairment in patients with SIVD. Patients with severer SIVD or more LI show poorer performance on cognitive function.
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Objective To investigate the histochemical characteristics of muscle fiber in patients with Becker type muscular dystrophy (BMD) and its clinical significance.Methods Muscular biopsies were performed in 3 patients with BMD. The specimens were stained by HE and nicotinamide-adenine dinucleotid-tetrazole reducase (NADH-TR) methods and observed under light microscope. Normal muscles from healthy people were saved as controls.Results The slice from BMD patients showed varied sizes of muscular fibers, remarkable hypertrophy fibers, splitting fibers, targetoid fibers, lobulated fibers, whorled fibers and ring fibers. Targetoid fibers were also found using NADH-TR staining.Conclusions The degree of fiber necrosis in BMD is mild. Degeneration and proliferation are the main pathological changes, which predict mild clinical symptoms, long course of disease and favourable prognosis.