MYRF-related mild encephalopathy with reversible myelin vacuolization: a case report and literature review.

Background: MYRF-related mild encephalopathy with reversible myelin vacuolization (MMERV) is an inherited neurological disorder characterized by dysfunction in the central nervous system and widespread reversible leukoencephalopathy. This paper presents a confirmed case of familial MMERV and summarizes pertinent features to offer guidance for future diagnosis and treatment of MMERV. Case Introduction: We have diagnosed a case of MMERV based on a history of seizures during early childhood and recurrent speech fluency issues in adulthood, reversible abnormal intensities in bilateral white matter in the centrum semiovale and corpus callosum, and the identification of myelin regulatory factor (MYRF) heterozygous variants. Conclusion: MYRF-related mild encephalopathy with reversible myelin vacuolization is a rare autosomal dominant genetic disease, with early clinical manifestations often being seizures. The definitive diagnosis of MMERV can be confirmed through genetic analysis. Minimizing infections can help reduce disease recurrence. However, future research should explore the impact of MYRF heterozygous variants in the wider MMERV population.

Efficacy and Safety of Panax notoginseng Saponins in the Treatment of Adults With Ischemic Stroke in China: A Randomized Clinical Trial.

Importance: Preclinical and clinical studies have suggested the neuroprotective effect of Panax notoginseng saponins (Xuesaitong soft capsules). However, robust evidence in patients with ischemic stroke is lacking. Objective: To assess the efficacy and safety of Xuesaitong soft capsules in patients with ischemic stroke. Design, Setting, and Participants: This multicenter, double-blind, placebo-controlled randomized clinical trial was conducted at 67 tertiary health centers in China from July 1, 2018, to June 30, 2020. Included patients were aged 18 to 75 years with a diagnosis of ischemic stroke and a National Institutes of Health Stroke Scale score between 4 and 15. Interventions: Eligible patients were randomly assigned within 14 days after symptom onset to receive either treatment with Xuesaitong soft capsules (120 mg orally twice daily) or placebo (120 mg orally twice daily) for 3 months. Main Outcomes and Measures: The primary outcome was functional independence at 3 months, defined as a modified Rankin Scale score of 0 to 2. Results: Among 3072 eligible patients with ischemic stroke who were randomized, 2966 (96.5%) were included in the modified intention-to-treat cohort (median [IQR] age, 62 [55-68] years; 1982 male [66.8%]). The number of patients who achieved functional independence at 3 months was 1328 (89.3%) in the Xuesaitong group and 1218 (82.4%) in the control group (odds ratio, 1.95; 95% CI, 1.56-2.44; P < .001). In the safety cohort, serious adverse events occurred in 15 of 1488 patients (1.0%) in the Xuesaitong group and 16 of 1482 (1.1%) in the control group (P = .85). Conclusions and Relevance: In this randomized clinical trial, Xuesaitong soft capsules significantly increased the likelihood of functional independence at 3 months in patients with ischemic stroke, indicating that this may be a safe and effective alternative therapy to improve prognosis in this population. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1800016363.

Predictive values of carotid high-resolution magnetic resonance imaging for large embolus shedding in carotid artery stenting.

BACKGROUND: Embolus shedding is one of the important complications in carotid artery stenting (CAS). Carotid high-resolution magnetic resonance imaging (HR-MRI) is often used to directly reflect important biological characteristics, such as plaque size and composition, as well as the structure of the carotid artery wall. The aim of this study was to investigate the predictive values of carotid HR-MRI for large embolus shedding in CAS. METHODS: In total, 195 patients with carotid stenosis were enrolled. Preoperative carotid HR-MRI was performed to define the nature of the carotid plaques. CAS was performed in all patients, and intraoperative embolic protection devices were used to collect the shed emboli. According to the diameter and number of shed emboli, the patients were divided into the small-embolus group (group X) and largeembolus group (group Y). Logistic regression analysis was used to analyze the risk factors of large embolus shedding. RESULTS: Group Y included 58 patients, and group X included 137 patients. Age, stenosis length, smoking, and ≥3 transient cerebral ischemic attacks were risk factors for large embolusshedding. Two cases of shed large emboli developed from stable plaques, and 56 cases of large emboli developed from vulnerable plaques. When vulnerable plaques were associated with more risk factors, the incidences of large embolus shedding in cases with vulnerable plaques combined with 0, 1, 2, 3, and 4 risk factors were 44 % (4/9), 68.1% (15/22), 72.2% (13/18), 76.5% (13/17), and 84.6% (11/13), respectively. DISCUSSION: Carotid HR-MRI can predict the incidence of large embolus shedding in CAS.

Trimethylamine N-oxide promotes demyelination in spontaneous hypertension rats through enhancing pyroptosis of oligodendrocytes.

Background: Hypertension is a leading risk factor for cerebral small vessel disease (CSVD), a brain microvessels dysfunction accompanied by white matter lesions (WML). Trimethylamine N-oxide (TMAO), a metabolite of intestinal flora, is correlated with cardiovascular and aging diseases. Here, we explored the effect of TMAO on the demyelination of WML. Methods: Spontaneous hypertension rats (SHRs) and primary oligodendrocytes were used to explore the effect of TMAO on demyelination in vivo and in vitro. T2-weighted magnetic resonance imaging (MRI) was applied to characterize the white matter hyperintensities (WMH) in rats. TMAO level was evaluated using LC-MS/MS assay. The histopathological changes of corpus callosum were measured by hematoxylin-eosin and luxol fast blue staining. And the related markers were detected by IHC, IF and western blot assay. Mito Tracker Red probe, DCFH-DA assay, flow cytometry based on JC-1 staining and Annexin V-FITC/PI double staining were conducted to evaluate the mitochondrial function, intracellular ROS levels and cell apoptosis. Results: SHRs exhibited stronger WMH signals and a higher TMAO level than age-matched normotensive Wistar-kyoto rats (WKY). The corpus callosum region of SHR showed decreased volumes and enhanced demyelination when treated with TMAO. Furthermore, TMAO significantly elevated ROS production and induced NLRP3 inflammasome and impairment of mitochondrial function of oligodendrocytes. More importantly, TMAO enhanced the pyroptosis-related inflammatory death of oligodendrocytes. Conclusion: TMAO could cross the blood-brain barrier (BBB) and promote oligodendrocytes pyroptosis via ROS/NLRP3 inflammasome signaling and mitochondrial dysfunction to promote demyelination, revealing a new diagnostic marker for WML under hypertension.

Risk Factors Affecting Cognitive Impairment of the Elderly Aged 65 and Over: A Cross-Sectional Study.

Objectives: Elderly population with cognitive impairment has been accelerating in China. This study aimed to explore the relationship between each risk factor and each cognitive domain to provide evidence for risk prevention of controlling impaired cognitive function in elderly. Methods: This cross-sectional study analyzed the cognitive status of the elderly aged 65 and above in three communities in Shizhong District of Jinan City. Cognitive status was assessed by MMSE. The influencing factors of cognitive impairment were analyzed by chi square test, correlation analysis and regression analysis. Results: Among 1,171 participants, 643 were defined as cognitive impairment with an incidence of 54.9%. And we found that there were significant differences in the incidence of cognitive impairment among residents with different gender, age, education level, hypertension and LDL-C (P < 0.05). However, BMI, marital status, smoking, physical exercise, T2DM, TC, TG and HDL-C had no significant differences in the incidence of cognitive impairment. In addition, education level (b = 1.194, P <0.001), age (b = -0.040, P = 0.001), LDL-C (b = 0.169, P = 0.018) had statistical significance on the total score of MMSE according to binary logistic regression analysis. Conclusion: Gender, age, education level, hypertension and LDL-C had significant differences in the incidence of cognitive impairment. And these risk factors could provide a basis for the early screening and intervention of cognitive impairment in the elderly.

A Systematic Review of Body Fluids Biomarkers Associated With Early Neurological Deterioration Following Acute Ischemic Stroke.

Biomarkers are objectively measured biological properties of normal and pathological processes. Early neurological deterioration (END) refers to the deterioration of neurological function in a short time after the onset of acute ischemic stroke (AIS) and is associated with adverse outcomes. Although multiple biomarkers have been found to predict END, there are currently no suitable biomarkers to be applied in routine stroke care. According to the Preferred Reporting Items for Systematic Review standards, we present a systematic review, concentrating on body fluids biomarkers that have shown potential to be transferred into clinical practice. We also describe newly reported body fluids biomarkers that can supply different insights into the mechanism of END. In our review, 40 scientific papers were included. Depending on the various mechanisms, sources or physicochemical characteristics of body fluids biomarkers, we classified related biomarkers as inflammation, protease, coagulation, metabolism, oxidative stress, and excitatory neurotoxicity. The body fluids biomarkers whose related articles are limited or mechanisms are unknown are categorized as other biomarkers. The inflammation-related biomarkers, such as neutrophil-to-lymphocyte ratio and hypersensitive C-reactive protein, play a crucial role among the mentioned biomarkers. Considering the vast heterogeneity of stroke progression, using a single body fluids biomarker may not accurately predict the risk of stroke progression, and it is necessary to combine multiple biomarkers (panels, scores, or indices) to improve their capacity to estimate END.

Erratum to "Spinocerebellar ataxia type 40: A case report and literature review".

[This corrects the article DOI: 10.1515/tnsci-2020-0190.].

Spinocerebellar ataxia type 40: A case report and literature review.

Spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases with ataxia as the main clinical manifestation. The phenotypes, gene mutations, and involved sites of different subtypes show a high degree of heterogeneity. The incidence of SCA varies greatly among different subtypes and the case of SCA40 is extremely rare. The aim of this study is to report a rare case of SCA40 and systematically review the incidence, gene mutation, and phenotype of SCAs, especially SCA40.

Transcriptome Sequencing Identifies Potential Biomarker for White Matter Lesions Diagnosis in the Hypertension Population.

Hypertension is confirmed to be one of the major risk factors of leukoaraiosis (LA). However, the pathogenesis of LA is not completely understood and there is no reliable indicator for the early diagnosis of LA in the hypertensive population. This study was designed to explore the potential biomarker for LA diagnosis in patients with hypertension. And it serves as the basis for the further study of LA mechanism. In this study, This study included 110 subjects, including 50 in the LA group and 60 in the control group. First, we performed transcriptome sequencing and quantitative PCR (qPCR) in four samples from the LA group, and three from the control group (seven people) to identify relevant long non-coding RNAs (long ncRNAs or lncRNA). The 103 samples were used for qPCR validation of relevant lncRNAs and the results were consistent with the sequencing. In-depth bioinformatics analysis were performed on differentially expressed (DE) lncRNAs and mRNAs. Go-functional enrichment analysis was performed on DE mRNAs. Some DE mRNA were enriched to biological processes associated with LA, And some lncRNAs related to DE mRNAs were traceable through cis/trans analysis, suggesting that they might be regulated in some way. Additionally, potential biomarkers for LA diagnosis in the hypertension population were identified via RT-qPCR and receive operating characteristic curve (ROC) analysis of lncRNA. One lncRNA, AC020928.1, has been demonstrated to be potential biomarkers for LA diagnosis in the hypertension population. The results of the present study indicated that the lncRNA may have an important role in the pathogenesis of LA and may be a novel target for further research. As the relationship between lncRNAs and LA is just beginning to be unraveled, their specific mechanisms require further investigation.

Sex Differences in Risk Factors for Transient Ischemic Attack in a Chinese Population.

Introduction: This study aimed to collect and evaluate basic information of a stroke screening population in eastern China and to compare distribution differences in risk factors between males and females in a transient ischemic attack (TIA) population. Methods: A standardization of the risk factors for stroke was performed according to an implementation plan of stroke in a high-risk population screening and intervention project in Shandong Province. Of the 231,289 residents, 8,603 patients with a previous TIA were identified and risk factors in this cohort were analyzed for sex differences. Results: In our initial cohort of 231,289 residents, we found 3,390 men and 5,213 women with TIA, accounting for a prevalence of 3.1 and 4.2%, respectively. Risk factors for TIA were hypertension, atrial fibrillation, diabetes, smoking, lack of exercise, overweight, and family history of stroke. In our TIA cohort, we found that the prevalence of smoking was significantly higher in men (41.3%) compared with that found in women (4.2%). Further, hypertension (58.8 vs. 55.5%) and family history of stroke (22.3 vs. 20.0%) were more prevalent in men compared with women, whereas atrial fibrillation (AF) (14.7 vs. 16.4%), diabetes (11.1 vs. 13.2%), lack of exercise (27.2 vs. 28.0%), and overweight (29.5 vs. 35.7%) were less prevalent. Conclusions: In our TIA cohort from eastern China, we found significant sex differences for the risk factors of hypertension, atrial fibrillation, smoking, diabetes, and overweight.

Loss of succinyl-CoA synthase ADP-forming ß subunit disrupts mtDNA stability and mitochondrial dynamics in neurons.

Succinyl Coenzyme A synthetase (SCS) is a key mitochondrial enzyme. Defected SCS ADP-forming ß subunit (SCS A-ß) is linked to lethal infantile Leigh or leigh-like syndrome. However, the impacts of SCS A-ß deficiency on mitochondria specifically in neurons have not yet been comprehensively investigated. Here, by down-regulating the expression levels of SCS A-ß in cultured mouse neurons, we have found that SCS A-ß deficiency induces severe mitochondrial dysfunction including lowered oxidative phosphorylation (OXPHOS) efficiency, increased mitochondrial superoxide production, and mtDNA depletion as well as aberrations of mitochondrial fusion and fission proteins, which eventually leads to neuronal stress. Our data also suggest that the deregulation of mitochondrial nucleoside diphosphate kinase (NDPK) together with defects in mitochondrial transcription factors including mitochondrial DNA pol γ and Twinkle contribute to SCS A-ß deficiency-mediated mtDNA instability. Furthermore, we have found that SCS A-ß deficiency has detrimental influence on neuronal mitochondrial dynamics. Put together, the results have furnished our knowledge on the pathogenesis of SCS A-ß deficiency-related mitochondrial diseases and revealed the vital role of SCS A-ß in maintaining neuronal mitochondrial quality control and neuronal physiology.

Spectrum construction of differentially expressed circular RNAs in patients with leukoaraiosis and function analysis of differentially expressed genes.

Circular RNAs (circRNAs) are class of endogenous RNAs that have a role in the regulation of gene expression. The present study aimed to investigate the diagnostic value and role of circRNA in the pathogenesis of leukoaraiosis (LA). The present study performed Arraystar Human circRNA Array analysis of 6 samples from LA cases and 6 samples from control cases. Differentially expressed (DE) circRNAs between two samples were identified through fold­change (>1.5­fold) screening. Afterwards, based on DE circRNAs, the gene ontology (GO) analysis of upregulated DE genes identified from DE circRNAs demonstrated that DE genes were primarily associated with cellular metabolic processes, membrane­bound organelles and binding. However, none were enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Downregulated DE genes were enriched in cellular localization, cytoplasm and kinase binding. For the KEGG pathways, the downregulated DE genes were primarily associated with the insulin signaling pathway. The results of the present study indicated that the DE genes from differently expressed circRNAs may have an important role in the pathogenesis of LA and may be a novel targfet for further research.

Erratum: Relationship between dyslipidemia and carotid plaques in a high-stroke-risk population in Shandong Province, China.

[This corrects the article DOI: 10.1002/brb3.473.].

Relationship between dyslipidemia and carotid plaques in a high-stroke-risk population in Shandong Province, China.

INTRODUCTION: The precise associations between stroke and carotid plaques and dyslipidemia are unclear. This population-based study aimed to examine the relationship between carotid plaques and dyslipidemia in a high-stroke-risk population. METHODS: Ultrasonography of left and right carotid arteries was conducted in 22,222 participants in a second screening survey of individuals with high stroke risk. Subjects were divided into two groups according to the presence or absence of carotid plaques. Blood TC (total cholesterol), TG (total triglycerides), and LDL-C (low-density lipoprotein cholesterol) levels were recorded. RESULTS: Multivariate logistic regression analysis, controlled for gender, age, education, geographic region, smoking, exercise, and overweight (Model 2), identified TG as a predictor of carotid-plaque risk (odds ratio [OR] = 1.109, 95% confidence interval [CI]: 1.038-1.185, P = 0.002), and the association between carotid plaques and LDL-C (OR = 0.967, 95%CI: 0.949-0.994, P = 0.019) was less significant, whereas there was no association between carotid plaques and TC (OR = 1.002, 95%CI: 0.932-1.007, P = 0.958). After additional adjustment for hypertension, diabetes, and atrial fibrillation (Model 3), TG remained a risk factor for carotid plaques (OR = 1.086, 95%CI: 1.016-1.161, P = 0.015), but no associations were observed between carotid plaques and LDL-C (OR = 0.972, 95%CI: 0.910-1.038, P = 0.394) or TC (OR = 1.003, 95%CI: 0.933-1.079, P = 0.928). Only the association between TG and carotid plaques (OR = 1.084, 95%CI: 1.014-1.159, P = 0.017) was independent of all covariates (covariates in Model 3 plus history of stroke or transient ischemic attack, and stroke family history) in Model 4. CONCLUSION: These findings indicate that TG was an independent risk factor for carotid plaques in high-risk population for stroke, whereas LDL-C and TC were not associated with the appearance of carotid plaques independently.

Differences in the distribution of risk factors for stroke among the high-risk population in urban and rural areas of Eastern China.

INTRODUCTION: Considering the program of screening for risk factors of stroke in Eastern China, the aim of this study was to compare the distribution differences in risk factors for stroke among the high-risk population living in urban and rural areas. METHODS: A total of 231,289 residents were screened and basic information collected. Risk factors for stroke among the high-risk population were compared between the urban and rural groups. RESULTS: A total of 117,776 high-risk residents from urban areas and 113,513 from rural areas were included in the analysis. The prevalence of hypertension was much higher in rural areas (73.3%) than that in urban areas (64.1%). Dyslipidemia (48.9% vs. 26.9%), sport lack (46.6% vs. 31.6%), diabetes mellitus (21.3% vs. 16.5%), and atrial fibrillation (18.7% vs. 9.8%) were more prevalent in the urban group, while smoking (26.5% vs. 28.8%), previous stroke (10.1% vs. 16.9%), and transient ischemic attack (20.9% vs. 24.6%) were less prevalent. CONCLUSION: Among the population at high risk of stroke, there were significant differences in the distribution of the following risk factors between the urban and rural groups: hypertension, atrial fibrillation, dyslipidemia, lack of physical exercise, and a previous stroke.

Leukoaraiosis with mild cognitive impairment.

As the ageing population continues to increase, the prevalence of age-related cognitive impairment has been on the rise. Mild cognitive impairment (MCI) is now widely recognised as the early stage of dementia. Mild cognitive impairment is closely associated with cerebral white matter lesions (WMLs), specifically in the case of leukoaraiosis (LA). A previous diffusion tensor imaging (DTI) has demonstrated that white matter changes might damage cognitive function in LA patients, and the cognitive function might decrease with the deterioration of LA. Through consulting and analysing documents, we found that both of them share similarities in risk factors, pathogenesis, pathological changes, and imaging manifestations. The main characteristics of LA patients with MCI (LACI) are the early and apparent manifestations of delayed memory, attention, impaired executive function, and close association with dementia. This analysis of LACI may contribute to an early diagnosis of LACI and provide possible treatment for LACI.

Carotid artery stenting ameliorates the cognitive impairment in patients with leukoaraiosis, the ischemic change of cerebral white matter.

Leukoaraiosis (LA) is a leading cause of gait disturbance in the elderly and well known as a type of cerebrovascular diseases. LA is mainly caused by the focal ischemic damage in cerebral white matter. Cognitive impairment in patients with LA is difficult to treat. Carotid artery stenting (CAS) has been reported to improve the cognitive function in patients with cognitive impairment. However, whether CAS can ameliorate the cognitive impairment in patients with LA remains unknown. To address this problem, we prospectively enrolled 105 LA patients with carotid stenosis and 206 healthy subjects, who are free of carotid artery stenosis and brain diseases or injuries, as the control. Neuropsychological functions were tested in these LA patients before and after 1-, 6- and 12-month CAS, and compared with the data of control subjects. Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Revised China (WAIS-RC) scores were lower in LA patients than those in healthy controls (P < 0.05), indicating the cognitive impairment in the LA patients. Compared with the scores before CAS, there is a time-dependent increase in MMSE and WAIS-RC scores after 1-, 6- and 12-month CAS (P < 0.05). Moreover, CAS treatment reduced Clinical Dementia Rating scale in LA patients. The cognitive impairment of LA patients with carotid stenosis was severe, but their cognitive impairment was ameliorated with carotid stenosis (P < 0.01). Thus, CAS can improve cognitive function of the LA patients with carotid stenosis.

Lingo-1 inhibited by RNA interference promotes functional recovery of experimental autoimmune encephalomyelitis.

Lingo-1 is a negative regulator of myelination. Repairment of demyelinating diseases, such as multiple sclerosis (MS)/experimental autoimmune encephalomyelitis (EAE), requires activation of the myelination program. In this study, we observed the effect of RNA interference on Lingo-1 expression, and the impact of Lingo-1 suppression on functional recovery and myelination/remyelination in EAE mice. Lentiviral vectors encoding Lingo-1 short hairpin RNA (LV/Lingo-1-shRNA) were constructed to inhibit Lingo-1 expression. LV/Lingo-1-shRNA of different titers were transferred into myelin oligodendrocyte glycoprotein-induced EAE mice by intracerebroventricular (ICV) injection. Meanwhile, lentiviral vectors carrying nonsense gene sequence (LVCON053) were used as negative control. The Lingo-1 expression was detected and locomotor function was evaluated at different time points (on days 1,3,7,14,21, and 30 after ICV injection). Myelination was investigated by luxol fast blue (LFB) staining.LV/Lingo-1-shRNA administration via ICV injection could efficiently down-regulate the Lingo-1 mRNA and protein expression in EAE mice on days 7,14,21, and 30 (P < 0.01), especially in the 5 × 10(8) TU/mL and 5 × 10(9) TU/mL LV/Lingo-1-shRNA groups. The locomotor function score in the LV/Lingo-1-shRNA treated groups were significantly lower than the untreated or LVCON053 group from day 7 on. The 5 × 10(8) TU/mL LV/Lingo-1-shRNA group achieved the best functional improvement (0.87 ± 0.11 vs. 3.05 ± 0.13, P < 0.001). Enhanced myelination/remyelination was observed in the 5 × 10(7) , 5 × 10(8) , 5 × 10(9) TU/mL LV/Lingo-1-shRNA groups by LFB staining (P < 0.05, P < 0.01, and P < 0.05).The data showed that administering LV/Lingo-1-shRNA by ICV injection could efficiently knockdown Lingo-1 expression in vivo, improve functional recovery and enhance myelination/remyelination. Antagonism of Lingo-1 by RNA interference is, therefore, a promising approach for the treatment of demyelinating diseases, such as MS/EAE.

[LINGO-1 expression of brain tissue in experimental autoimmune encephalomyelitis mouse].

OBJECTIVE: To observe the changes of LINGO-1 expression with time after onset in EAE mouse. METHODS: C57/BL6 mice were completely randomly divided into EAE model group (n = 15) , adjuvant group (n = 15) and control group (n = 15) .LINGO-1 expression of brain tissue was detected on day 1, 7, 14, 21 and 30 after onset by RT-PCR and Western blot.RhoA and p-RhoA expression of brain tissue was analysed by Western blot. RESULTS: The LINGO-1mRNA levels in EAE model group were markedly higher than control group on day 1, 7and 14 after onset (4.63 ± 0.25, 2.72 ± 0.12, 1.98 ± 0.16, P < 0.01, P < 0.01, P < 0.05).On day 30, Lingo-1 mRNA was close to control group.Expression levels of Lingo-1 protein on day 1, 7, 14, 21, 30 were higher than control group (2.11 ± 0.15, 3.15 ± 0.09, 2.45 ± 0.12, 1.89 ± 0.17, 1.21 ± 0.05, P < 0.05, P < 0.01, P < 0.05, P < 0.05, P < 0.05. The levels of p-RhoA protein increased in EAE and the peak appeared on day 1 and day 7 (P < 0.01) . And there was no difference on RhoA expression among different groups. CONCLUSIONS: LINGO-1 expression of brain tissue of EAE mouse upregulates and changes with time after onset, which may inhibit myelination by RhoA activation.In clinic, the antagonist of LINGO-1 for MS should be applied as soon as possible.

Soluble oligomers and fibrillar species of amyloid ß-peptide differentially affect cognitive functions and hippocampal inflammatory response.

Two major active species of ß-amyloid protein (Aß), fibrillar Aß1-42 (FAß) and soluble Aß1-42 oligomers (AßO), are known to play important roles in the pathogenesis of Alzheimer's disease. However, the differences between them are largely unknown. In this study, we explored the effects of FAß and AßO on cognitive functions and hippocampal inflammatory response through a 30-days infusion of FAß or AßO (144pmol/d) into the left lateral ventricles of the rat brain. Morris water maze showed that the impairment of learning and memory functions was much more significant in the AßO-infused rats, compared to the FAß-infused rats. AßO-induced neurodegeneration and ultrastructure damage in CA1 neurons were more remarkable than those induced by FAß. Compared to FAß, AßO exerted more potent effects on the expressions of inflammatory factors toll-like receptor 4 and TNF-α and activation of NF-κB signaling. Taken together, our results from in vivo model demonstrate that AßO is more neurotoxic than FAß, and this neurotoxicity may be related to NF-κB-medicated inflammatory response.