Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion.

BACKGROUND/AIMS: An enriched environment (EE) ameliorates learning and memory impairments induced by chronic cerebral hypoperfusion, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway exerts both beneficial and deleterious effects on the nervous system during the progression of ischemia. METHODS: The present study investigated whether p38 MAPK participates in the process by which EE exposure ameliorates the cognitive deficits induced by chronic cerebral hypoperfusion. RESULTS: EE exposure significantly enhanced the cognitive performance of vascular dementia (VD) model rats, and p38 MAPK protein decreased in parallel with cognitive improvements. Inhibition of p38 MAPK function by its selective inhibitor SB203580 improved the cognition index of VD rats and upregulated p38 MAPK expression with p38 MAPK antisense oligodeoxynucleotides. This impaired cognition in VD rats could not be rescued by EE exposure. CONCLUSION: p38 MAPK participates in the process by which EE exposure ameliorates cognitive deficits induced by chronic cerebral hypoperfusion.

Atypical chronic inflammatory demyelinating polyradiculoneuropathy with ophthalmoplegia and anti-sulfatide IgM positivity.

BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous group of chronic immune-mediated polyradiculoneuropathies. The clinical presentation of CIDP is mainly characterized by a classic peripheral demyelinating sensory-motor type and persists for a minimum of 2 months. However, CIDP may also present with atypical symptoms.Case presentation: This report presents the case of a patient with CIDP with ophthalmoplegia and anti-sulfatide IgM antibodies. Maintenance intravenous immunoglobulin and glucocorticoid therapies were administered to the patient in accordance with the clinical, laboratory, and electrophysiological findings, which were indicative of CIDP. The treatment partially improved the symptoms, and no recurrence was detected throughout the 3-month monitoring phase. CONCLUSIONS: This study combines a retrospective analysis and a literature review to explore the possible mechanism of CIDP.

A Two-Gene-Based Diagnostic Signature for Ruptured Intracranial Aneurysms.

Background: Ruptured intracranial aneurysm (IA) is a disease with high mortality. Despite the great progress in treating ruptured IA, methods for risk assessment of ruptured IA remain limited. Methods: In this study, we aim to develop a robust diagnostic model for ruptured IA. Gene expression profiles in blood samples of 18 healthy persons and 43 ruptured IA patients were obtained from the Gene Expression Omnibus (GEO). Differential expression analysis was performed using limma Bioconductor package followed by functional enrichment analysis via clusterProfiler Bioconductor package. Immune cell compositions in ruptured IA and healthy samples were assessed through the CIBERSORT tool. Protein-protein interaction (PPI) was predicted based on the STRING database. Logistic regression model was used for the construction of predictive model for distinguishing ruptured IA and healthy samples. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed to validate the gene expression between the ruptured IA and healthy samples. Results: A total of 58 differentially expressed genes (DEGs) were obtained for ruptured IA patients compared with healthy controls. Functional enrichment analysis showed that the DEGs were enriched in biological processes related to neutrophil activation, neutrophil degranulation, and cytokine-cytokine receptor interaction. Notably, immune analysis results proved that the rupture of IA might be related to immune cell distribution. We further identified 24 key genes as hub genes using the PPI networks. The logistic regression model trained based on the 24 key genes ultimately retained two genes, i.e., IL2RB and CCR7, which had great potential for risk assessment for rupture of IA. The RT-qPCR further validated that compared with the healthy samples, the expression levels of IL2RB and CCR7 were decreased in ruptured IA samples. Conclusions: This study might be helpful for cohorts who have a high risk of ruptured IA for early diagnosis and prevention of the disease.

Effects of resveratrol on learning and memory in rats with vascular dementia.

The purpose of the present study was to study the effects of resveratrol on cognitive function in rats with vascular dementia and to investigate the molecular mechanisms of its neuroprotective effects. Forty­five SD rats were randomly divided into 3 groups: The control group (Con group, n=15), the model group (VD group, n=15) and the resveratrol­treated VD group (Res group, n=15). The VD rats (the VD group and the Res group) were generated by bilateral common carotid artery occlusion. The rats in the Res group received daily resveratrol treatment intraperitoneally for 4 weeks. Cognitive function was tested using the Morris water maze test. The levels of SOD and MDA (oxidative stress indicators) were detected by ELISA kits. The protein expression of Bax, Bcl­2 and caspase­3 was detected by western blotting. Compared with the rats in the Con group, the rats in the VD group exhibited decreased cognitive function, significantly increased hippocampal content of MDA, Bax and caspase­3 (P<0.05), and significantly reduced hippocampal expression of SOD and Bcl­2 (P<0.05). Compared with the rats in the VD group, the rats in the Res group exhibited increased cognitive ability, reduced hippocampal content of MDA, Bax and caspase­3 (P<0.05), and increased hippocampal expression of SOD and Bcl­2 (P<0.05). Resveratrol treatment significantly improved the spatial learning and memory of the VD rats. The mechanism associated with the neuroprotective effects of resveratrol may be closely related to the inhibition of the apoptosis pathway and oxidative stress injury.

Neuroprotective effects of salidroside administration in a mouse model of Alzheimer's disease.

Salidroside administration improves memory in different models of learning. However, its influence on models of Alzheimer's disease (AD) has not been widely studied. In the present study, the therapeutic effect of salidroside was investigated in an animal model of AD. APPswe/PS1ΔE9 mouse (n=20) were randomly divided into either the AD model group or the salidroside + AD model group (n=10 in each group), and C57BL/6J mouse (n=20) of identical age and genetic background were randomly divided into either the normal control (NC) group or the salidroside + NC group (n=10 in each group). The Morris water maze behavioral test was applied to all mice in order to investigate the effects of salidroside administration on learning and memory functions. The concentrations of malondialdehyde (MDA), glutathione (GSH) and nitrate in the hippocampus of the mice were determined, and hippocampal superoxide dismutase (SOD) activity was also determined. In addition, terminal deoxynucleotidyl­transferase­mediated dUTP nick end labeling was used to investigate the rate of neuronal apoptosis in the hippocampus. Furthermore, the concentrations of interleukin­6 (IL­6) and tumor necrosis factor­α (TNF­α) were tested for in the brain tissues of AD mice. Learning and memory functions in AD mice were revealed to improve following administration of salidroside. Furthermore, salidroside administration was revealed to decrease the concentrations of MDA and nitrate in the hippocampus, decrease the apoptotic rate of hippocampal neurons, and increase the activity of SOD and the concentration of GSH in hippocampal tissue. In addition, it was demonstrated that salidroside administration suppressed the expression levels of IL­6 and TNF­α. In conclusion, this study revealed that the administration of salidroside could attenuate the effects of AD­associated memory and learning impairment in mice. Furthermore, it was demonstrated that the effects of salidroside administration on AD mice were, at least partially, via inhibition of brain oxidative/nitrosative damage, suppression of both IL­6 and TNF­α expression levels, and suppression of the hippocampal neuronal apoptotic rate.