Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is not just confined to the older population. Although developments have been made in AD treatment, various limitations remain to be addressed. These are partly contributed by biological hurdles, such as the blood–brain barrier and peripheral side effects, as well as by lack of carriers that can efficiently deliver the therapeutics to the brain while preserving their therapeutic efficacy. The increasing AD prevalence and the unavailability of effective treatments have encouraged researchers to develop improved, convenient, and affordable therapies. Functional materials based on primitive cells and nanotechnology are emerging as attractive therapeutics in AD treatment. Cell primitives possess distinct biological functions, including long-term circulation, lesion site targeting, and immune suppression. This review summarizes the challenges in the delivery of AD drugs and recent advances in cell primitive–based materials for AD treatment. Various cell primitives, such as cells, extracellular vesicles, and cell membranes, are presented together with their distinctive biological functions and construction strategies. Moreover, future research directions are discussed on the basis of foreseeable challenges and perspectives.

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BACKGROUND:Post-stroke cognitive impairment (PSCI) is not only a common consequence of stroke but also an important factor for adverse prognosis of patients. Biochemical indicators such as blood lipids and blood pressure are affected by many factors, and the ability of evaluating the progress of patients with PSCI is insufficient. Therefore, it is necessary to find sensitive markers for predicting the progress of patients and avoiding PSCI. Recent studies have shown that β-amyloid protein 1-42 (Aβ1-42) and thyroid hormone levels are closely related to PSCI, which may be the influencing factors of PSCI, but there are few related studies. AIM:To investigate the relationship between serum levels of Aβ and thyroid hormones in acute stage and PSCI and its predicted value. METHODS:A total of 195 patients with acute cerebral infarction confirmed from June 2016 to January 2018 were enrolled in this study. Baseline data and serological indicators were recorded to assess cognitive function of patients. All patients were followed up for 1 year. Their cognitive functions were evaluated within 1 wk, 3 mo, 6 mo and 1 yr after stroke. At the end of follow-up, the patients were divided into PSCI and non-PSCI according to Montreal cognitive assessment score, and the relationship between biochemical indexes and the progression of PSCI was explored. RESULTS:Compared with patients with non-PSCI, the levels of Aβ1-42, triiodothyronine (T3) and free thyroxin were lower in the patients with PSCI. Repeated measures analysis of variance showed that the overall content of Aβ1-42 and T3 in PSCI was also lower than that of the non-PSCI patients. Further analysis revealed that Aβ1-42 (r = 0.348), T3 (r = 0.273) and free thyroxin (r = 0.214) were positively correlated with disease progression (P < 0.05), suggesting that these indicators have the potential to predict disease progression and outcome. Cox regression analysis showed that Aβ1-42 and T3 were important factors of PSCI. Then stratified analysis showed that the lower the Aβ1-42 and T3, the higher risk of PSCI in patients who were aged over 70, female and illiterate. CONCLUSION:Aβ1-42 and T3 have the ability to predict the progression of PSCI, which is expected to be applied clinically to reduce the incidence of PSCI and improve the quality of life of patients.

Purpose Alzheimer’s disease (AD) is a neurodegenerative disorder that manifests as abnormal behavior and a progressive decline in memory. Although the pathogenesis of AD is due to the excessive deposition of amyloid β protein (Aβ) outside the neurons in the brain, evidence suggests that tau proteins may be a better target for AD therapy. In neurodegenerative diseases, a decrease in autophagy results in the failure to eliminate abnormally deposited or misfolded proteins. Therefore, induction of autophagy may be an effective way to eliminate tau proteins in the treatment of AD. We investigated the effects of polyethylene glycol (PEG)-ceramide nanomicelles on autophagy and on tau proteins in N2a, a murine neuroblastoma metrocyte cell line. Methods Ceramide is a sphingolipid bioactive molecule that induces autophagy. PEG-ceramide is a polymer that is composed of the hydrophobic chain of ceramide and the hydrophilic chain of PEG-2000. In this study, we prepared PEG-ceramide nanomicelles that were 10–20 nm in size and had nearly neutral zeta potential. Results The results show that PEG-ceramide nanomicelles caused an increase in the LC3-II/LC3-I ratio, while p62 protein levels decreased. Confocal microscopy revealed a significant increase in the number of dots corresponding to autophagosomes and autolysosomes, which indicated autophagic activation. Moreover, PEG-ceramide nanomicelles induced tau degradation in N2a cells through autophagy. Conclusion In summary, we have confirmed that PEG-ceramide nanomicelles enhanced autophagic flux and degraded overexpressed human tau proteins in N2a cells by regulating the autophagy pathway. Thus, PEG-ceramide nanomicelles show great promise as agents to induce autophagy and degrade tau proteins in the treatment of AD.

Objective . To investigate the effects of Dendrobium officinale polysaccharides (DOPS) on the expression of inflammatory factors IL-1 β and TNF- α and the MKP-1/MAPK signal pathway. Methods . PTZ-induced epileptic rat models were established. The rats were randomly divided into four groups: the control group, the DOPS group, the model group, and the DOPS intervention group. RT-PCR was used to measure the mRNA expression of IL-1 β and TNF- α in the hippocampi of all groups; western blot was used to measure the protein expression of IL-1 β and TNF- α and phosphorylation of ERK1/2, JNK, p38, and MKP-1 in the hippocampi of all groups at weeks 1, 2, 3, and 4 after modeling. Results . At weeks 1, 2, 3, and 4 after modeling, there were no significant differences between the control group and the DOPS group in the mRNA and protein expression of IL-1 β and TNF- α and phosphorylation of ERK1/2, JNK, p38, and MKP-1 (all P>0.05); the mRNA and protein expression of IL-1 β and TNF- α and phosphorylation of ERK1/2, JNK, and p38 were significantly increased, while the phosphorylation of MKP-1 was decreased in the model group compared with the control group. The mRNA and protein expression of IL-1 β and TNF- α and phosphorylation of ERK1/2, JNK, and p38 were significantly decreased, while the phosphorylation of MKP-1 was increased in the DOPS intervention group compared with the model group. Conclusion . DOPS can reduce PTZ-induced brain inflammation and seizures of epileptic rats by inhibiting IL-1 β , TNF- α , and MAPK signal pathways.

OBJECTIVES:Toxic encephalopathy induced by exposure to 1,2-dichloroethane(1,2-DCE) may result in central nervous system (CNS) abnormalities. The study was to describe the clinical and neuroimaging features in toxic encephalopathy induced by 1, 2-DCE. PATIENTS AND METHODS:The study evaluates six patients with clinical symptoms and neuroimaging who are exposed to 1, 2-DCE, including medical and neurologic examination, CT imaging, proton MR spectroscopy (MRS), Diffusion weighted MR (DW MR) and T1-and T2-weighted MR imaging. RESULTS:All patients who had been exposed to DCE subsequently had seizures or symptoms of intracranial hypertension,including headache, nausea, and vomiting. CT findings: All lesions appeared as low density and bilateral symmetry. The lesions appeared in white matter of cerebral hemisphere diffusely, bilateral cerebellar dentate nuclei, thalamus and globus pallidus. MRI features: All lesions showed high signal intensity on T2WI. Cerebral sulci swelling and compressed or occluded ventricles were seen on CT and MRI. DW MR images obtained at b = 1000s/mm2 revealed symmetrical high signal intensity changes. The apparent diffusion coefficient (ADC) values of lesions were decreased. MR spectroscopic findings established the spectral patterns: increased choline-containing compounds and decreased N-acetylaspartate. CONCLUSION:The clinical symptoms of intracranial hypertension and the features of CT and MR imagings are useful for early diagnosis and prompt treatment in toxic encephalopathy.

Objectives: We aimed to evaluate the metabolism differences in pontine tegmentum among patients with idiopathic RBD (iRBD), secondary RBD (sRBD) and healthy control groups using magnetic resonance spectroscopy (H-1-MRS) and whether metabolic changes are correlated with age in patients with RBD.Patients and methods: The iRBD, sRBD, and control groups were composed of 18, 26, and 29 patients, respectively. All participants underwent magnetic resonance imaging (MRI) and H-1-MRS detection at 17:00 for approximately 15 min. All NAA/Cr, Cho/Cr and NAA/Cho ratios were automatically generated using FuncTool and the correlation between metabolism and age was analyzed by Pearson's correlation analysis.Results: Significant difference in NAA/Cr ratio was found between the sRBD group and the other groups (p < 0.05). Significant difference in NAA/Cho ratio was found among all groups (p < 0.05). Cho/Cr ratio remarkably increased in the control group (p < 0.05) compared with the other groups. NAA/Cr ratio had an adverse correlation with age in the control, iRBD, and sRBD groups (r = -0.822, p = 0.000 vs r = -0.663, p = 0.003 vs r = -0.583, p = 0.002). However, there was no correlation between participants age and Cho/Cr (r = -0.054, p = 0.651) or NAA/Cho (r = 0.029, p = 0.805).Conclusion: Neurons in the sRBD group were lost or damaged; however, this damage was not obvious in the iRBD group. Nevertheless, NAA and Cho levels were reduced in the local nerve cells of both RBD groups; these changes might indicate the sensitive pathogenic areas among patients with RBD. (C) 2016 Elsevier B.V. All rights reserved.

Objective: This study aimed to investigate the influence of low-intensity pure tone auditory stimulation on patients with rapid eye movement (REM), sleep behavior disorder (RBD), and attempt to identify a new method of RBD intervention.Methods: Patients diagnosed with idiopathic RBD (iRBD) or symptomatic RBD (sRBD) were given auditory stimulation of low-intensity pure tones during their REM sleep. Sleep parameters including sleep process, sleep architecture as well as eye movements (EMs) frequency, and amplitude were recorded by polysomnography monitoring at pre-, intra-, and post-stimulation.Results: Thirteen iRBD and 18 sRBD patients completed this study. Auditory stimulation significantly reduced the EMs frequency and amplitude in iRBD and sRBD patients (p < 0.05). In the iRBD group, the intra-stimulated FSL increased significantly than the pre-stimulated FSL (p < 0.05). After stimulation, patients had similar sleep latency (FSL), rapid eye movement sleep latency (RSL) and periodic limb movements in sleep (PLMS) compared with control. In the sRBD group, the intra-stimulated total sleep time, sleep efficiency was significantly increased, whereas the RSL and PLMS were significantly reduced compared with the pre-stimulated ones (all p < 0.05). The sRBD patients had similar time in bed, FSL and RBD episodes compared with control (all p < 0.05) in spite of significant difference before stimulation (all p < 0.05). However, the sleep architecture was not influenced by the stimulation despite the decrease in N3% in iRBD group (p < 0.05).Conclusion: Low-intensity pure tone auditory stimulation may be a potentially effective intervention for RBD, especially for sRBD.

Previous work showed that sleep deprivation (SD) impairs hippocampal-dependent cognitive function and synaptic plasticity, and a novel wake-promoting agent modafinil prevents SD-induced memory impairment in rat. However, the mechanisms by which modafinil prevented REM-SD-induced impairment of brain function remain poorly understood. In the present study, rats were sleep-deprived by using the modified multiple platform method and brain function was detected. The results showed that modafinil treatment prevented REM-SD-induced impairment of cognitive function. Modafinil significantly reduced the number of errors compared to placebo and upregulated synapsin I expression in the dorsal hippocampal CA3 region. A synaptic plasticity-related gene, MMP-9 expression was also upregulated in modafinil-treated rats. Importantly, downregulation of MMP-9 expression by special siRNA decreased synapsin I protein levels and synapse numbers. Therefore, we demonstrated that modafinil increased cognition function and synaptic plasticity, at least in part by increasing MMP-9 expression in REM-SD rats.

Objective To observe changes in the working memory and brain functional imaging on functional magnetic resonance imaging(fMRI) after 36 hours sleep deprivation (SD) in healthy volunteers and to explore the possible mechanism of the changes.Methods FMRI scannings were performed in ten male healthy young volunteers before and after 36 hours SD and results were analyzed using SPM2 software.Subjects were also tested LTR and PLUS task to measure the persistence and operation of working memory before and after 36 hours SD.Results The reaction time of LTR task after 36 hours SD ( (866 ± 102) ms)was significantly longer than that before SD ( (754 ± 91 ) ms, t = 2.59, P < 0.01 ).The reaction time of PLUS task after SD ( (848 ± 94) ms) was significantly longer ( t = 2.37, P < 0.05 ) than that before SD ( (756 ± 79) ms).The error rate of LTR task after SD (95.3% ± 3.56% ) was significantly higher (t=3.52,P < 0.01 ) than that before SD (84.8% ± 8.71% ).The error rate of PLUS task after SD (95.7% ±4.72% ) was significantly higher (t =3.38 ,P <0.01 ) than that before SD (84.2% ±9.66% ).There were no significant differences between the two tasks.The frontal and parietal lobes, anterior cingulate gyrus and thalamus were activated during memory tasks testing before SD.Brain activation was broader and stronger in PLUS task than in LTR task.After SD, activation in parietal lobe was decreased and activation in prefrontal and thalamus was increased significantly.Conclusions The working memory performance decreased after SD.Both LTR and PLUS tasks of working memory activate frontal and parietal lobes, anterior cingulate gyrus and thalamus.The activation of parietal lobe decreased and the activation of prefrontal lobe and thalamus increased after 36 hours SD.This is the possible mechanism of SD to causes the cognition decline.

Objectives: To clarify effects of partial sleep deprivation (SD) on morning (07:00) serum cortisol concentrations in two protocols that restricted sleep to 3 h/day in healthy adult men. The study was also designed to delineate the relationship between anxiety levels in the morning and slow wave sleep (SWS) periods at night.Methods: Ten young adult Han Chinese males were recruited to participate in an 'earlier-night' sleep restriction (SR) period (sleep from 00:00 to 03:00) and then a 'later-night' SR period (sleep from 03:00 to 06:00). The duration of each SR period was 4 days, followed by a recovery night. The SR periods were separated by 10 days of normal sleep. Blood samples of serum cortisol were drawn at 07:00 during each of two SR periods for six consecutive mornings (for a total of 12 measurements per subject), and anxiety levels were also assessed over the same period by the State portion of the State-Trait Anxiety Inventory (STAI). Sleeping processes were monitored by polysomnogram.Results: Serum cortisol levels decreased after SR (P<0.05) in both paradigms, with greater decreases evident after later-night sleep loss than after earlier-night sleep loss. Cortisol levels were significantly, negatively correlated to the number of days of earlier-night SR, but not to later-night SR. Anxiety scores increased gradually in both conditions. The time of SWS changed indiscriminately in both paradigms. Cortisol levels returned to baseline after one night of recovery sleep.Conclusions: Cortisol decreased in both SR conditions, especially in the earlier-night SR protocol, even though SWS time and anxiety levels changed roughly in the same manner in both conditions. Data suggested that sleep loss at different times of the night affects the hypothalamic-pituitary-adrenal axis (HPA-axis) differentially. (C) 2008 Elsevier Inc. All rights reserved.