Peripheral and central pathogenesis of postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a classic chronic condition with multiple signs of peripheral and central neuropathy. Unfortunately, the pathogenesis of PHN is not well defined, limiting clinical treatment and disease management. OBJECTIVE: To describe the peripheral and central pathological axes of PHN, including peripheral nerve injury, inflammation induction, central nervous system sensitization, and brain functional and structural network activity. METHODS: A bibliographic survey was carried out, selecting relevant articles that evaluated the characterization of the pathogenesis of PHN, including peripheral and central pathological axes. RESULTS: Currently, due to the complexity of the pathophysiological mechanisms of PHN and the incomplete understanding of the exact mechanism of neuralgia. CONCLUSION: It is essential to conduct in-depth research to clarify the origins of PHN pathogenesis and explore effective and comprehensive therapies for PHN.

Subsecond total-body imaging using ultrasensitive positron emission tomography.

A 194-cm-long total-body positron emission tomography/computed tomography (PET/CT) scanner (uEXPLORER), has been constructed to offer a transformative platform for human radiotracer imaging in clinical research and healthcare. Its total-body coverage and exceptional sensitivity provide opportunities for innovative studies of physiology, biochemistry, and pharmacology. The objective of this study is to develop a method to perform ultrahigh (100 ms) temporal resolution dynamic PET imaging by combining advanced dynamic image reconstruction paradigms with the uEXPLORER scanner. We aim to capture the fast dynamics of initial radiotracer distribution, as well as cardiac motion, in the human body. The results show that we can visualize radiotracer transport in the body on timescales of 100 ms and obtain motion-frozen images with superior image quality compared to conventional methods. The proposed method has applications in studying fast tracer dynamics, such as blood flow and the dynamic response to neural modulation, as well as performing real-time motion tracking (e.g., cardiac and respiratory motion, and gross body motion) without any external monitoring device (e.g., electrocardiogram, breathing belt, or optical trackers).

Establishment of a sequential dual tracer 18 F-NaF/18 F-FDG PET protocol for imaging the equine foot.

The combination of 18 F-Sodium Fluoride (18 F-NaF) and 18 F-FluoroDeoxyGlucose (18 F-FDG) for positron emission tomography (PET) imaging of the equine foot is appealing for detection of both osseous and soft tissue lesions in a single scan. As the combination of tracers could lead to a loss of information, a sequential approach, consisting in imaging with one tracer prior to injecting the second tracer, might be valuable. The goals of this prospective, methods comparison, exploratory study were to establish the order of tracer injection and timing for imaging. Six research horses were imaged under general anesthesia with 18 F-NaF PET, 18 F-FDG PET, dual 18 F-NaF/18 F-FDG PET, and CT. Proper uptake could be identified in tendon lesions as early as 10 min after 18F-FDG injection. Bone uptake was limited when 18F-NaF was injected under general anesthesia, even at 1 h after injection, when compared with 18 F-NaF injection prior to anesthesia. The sensitivity and specificity of the dual tracer scans were 0.77 (0.63 to 0.86) and 0.98 (0.96 to 0.99) respectively, to assess 18 F-NaF uptake and 0.5 (0.28 to 0.72) and 0.98 (0.95 to 0.99), respectively, for 18F-FDG uptake. These results suggest that the sequential dual tracer approach is a pertinent technique to optimize the PET data gained from a single anesthetic episode. Based on dynamics of tracer uptake, the optimal protocol consists in injecting 18F-NaF prior to anesthesia, acquire 18F-NaF data then inject 18F-FDG and start acquisition of dual tracer PET data 10 min later. This protocol should be further validated in a larger clinical study.

Acupuncture Administration Improves Cognitive Functions and Alleviates Inflammation and Nuclear Damage by Regulating Phosphatidylinositol 3 Kinase (PI3K)/Phosphoinositol-Dependent Kinase 1 (PDK1)/Novel Protein Kinase C (nPKC)/Rac 1 Signaling Pathway in Senescence-Accelerated Prone 8 (SAM-P8) Mice.

BACKGROUND Alzheimer's disease (AD) is an age-associated neurodegenerative disorder. This study aimed to investigate effects of acupuncture administration on cognitive function and associated mechanisms. MATERIAL AND METHODS Senescence-accelerated prone 8 (SAM-P8) mice were randomly divided into 3 groups: the SAM-P8 group (P8-CN), the SAM-P8 administrating with acupuncture (P8-Acup) group, and the SAM-P8 administrating without acupuncture (P8-Sham) group. Morris water maze test was conducted to evaluate cognitive functions (memory and learning ability). PDK1, nPKC, and Rac1 inhibitors were used to treat SAM-P8 mice. Transmission electron microscope analysis was used to examine nuclear damage hippocampal tissues. Hematoxylin and eosin (H&E) staining was employed to evaluate inflammation. Western blot was used to detect PI3K, PDK1, nPKC, and Rac 1 expression in hippocampal tissues. RESULTS Acupuncture administration significantly reduced PI3K, PDK1, nPKC, and Rac 1 levels compared to P8-CN group (P<0.05). Both acupuncture and enzyme inhibitors (NSC23766, Rottlerin, OSU03012) significantly improved cognitive functions, reduced inflammation, and alleviated nuclear damages of SAM-P8 mice compared to P8-CN group (P<0.05). Acupuncture significantly enhanced effects of inhibitors on inflammation and nuclear damages compared to inhibitor treatment single (P<0.05). Acupuncture significantly enhanced down-regulative effects of OSU03012 on PI3K and PDK1 levels, increased down-regulative effects of Rottlerin on nPKC and Rac 1 levels and enhanced effects of Rottlerin on Rac 1 compared to P8-CN group (P<0.05). CONCLUSIONS Acupuncture administration improved cognitive functions and alleviated inflammatory response and nuclear damage of SAM-P8 mice, by downregulating PI3K/PDK1/nPKC/Rac 1 signaling pathway. This study could provide potential insight for treating cognitive dysfunction and aging of AD patients.

Positron emission tomography image reconstruction using feature extraction.

PURPOSE: To reduce the cost of positron emission tomography (PET) scanning systems, image reconstruction algorithms for low-sampled data have been extensively studied. However, the current method based on total variation (TV) minimization regularization nested in the maximum likelihood-expectation maximization (MLEM) algorithm cannot distinguish true structures from noise resulting losing some fine features in the images. Thus, this work aims to recover fine features lost in the MLEM-TV algorithm from low-sampled data. METHOD: A feature refinement (FR) approach previously developed for statistical interior computed tomography (CT) reconstruction is applied to PET imaging to recover fine features in this study. The proposed method starts with a constant initial image and the FR step is performed after each MLEM-TV iteration to extract the desired structural information lost during TV minimization. A feature descriptor is specifically designed to distinguish structure from noise and artifacts. A modified steepest descent method is adopted to minimize the objective function. After evaluating the impacts of different patch sizes on the outcome of the presented method, an optimal patch size of 7×7 is selected in this study to balance structure-detection ability and computational efficiency. RESULTS: Applying MLEM-TV-FR algorithm to the simulated brain PET imaging using an emission activity phantom, a standard Shepp-Logan phantom, and mouse results in the increased peak signal-to-noise ratio (PSNR) and structural similarity (SSIM) as comparing to using the conventional MLEM-TV algorithm, as well as the substantial reduction of the used sampling numbers, which improves the computational efficiency. CONCLUSIONS: The presented algorithm can achieve image quality superior to that of the MLEM and MLEM-TV approaches in terms of the preservation of fine structure and the suppression of undesired artifacts and noise, indicating its useful potential for low-sampled data in PET imaging.

Few-view CT image reconstruction using improved total variation regularization.

X-ray radiation is harmful to human health. Thus, obtaining a better reconstructed image with few projection view constraints is a major challenge in the computed tomography (CT) field to reduce radiation dose. In this study, we proposed and tested a new algorithm that combines penalized weighted least-squares using total generalized variation (PWLS-TGV) and dictionary learning (DL), named PWLS-TGV-DL to address this challenge. We first presented and tested this new algorithm and evaluated it through both data simulation and physical experiments. We then analyzed experimental data in terms of image qualitative and quantitative measures, such as the structural similarity index (SSIM) and the root mean square error (RMSE). The experiments and data analysis indicated that applying the new algorithm to CT data recovered images more efficiently and yielded better results than the traditional CT image reconstruction approaches.

Acupuncture for patients with mild to moderate Alzheimer's disease: a randomized controlled trial.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia. However, none of medical treatment can stop or reverse the underlying neurodegenerative of AD at present. Acupuncture has attracted more and more attention in recent years due to its efficacy and very few side effects. Lately, a systematic review has thought that the evidence on the effectiveness of acupuncture in improving the cognitive function of AD patients was not powerful enough. Therefore, the aim of this study is to explore the efficacy and safety of acupuncture in patients with mild to moderate AD. METHODS: This was a randomized, controlled, parallel-group, exploratory study with 4-week baseline (T0), 12-week treatment phase (T1) and 12-week follow-up period (T2). Patients with mild to moderate AD meeting the included criteria were randomly allocated into either acupuncture or donepezil hydrochloride groups. The acupuncture group(AG) was given acupuncture treatment three times per week and the donepezil hydrochloride group(DG) group was administered donepezil hydrochloride once daily (5 mg/day for the first 4 weeks and 10 mg/day thereafter). Primary efficacy was measured using Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog) and Clinician's Interview-Based Impression of Change-Plus (CIBIC-Plus). The second outcomes were measured with 23-Item Alzheimer's disease Cooperative Study Activities of Daily Living Scales (ADAS-ADL23) and Neuropsychiatric Index (NPI). RESULTS: Of 87 participants enrolled in the study, 79 patients finished their treatment and follow-up processes. The ADAS-cog scores for AG group showed obvious decreases at T2 and ∆(T2-T0)when compared with DG group, and significant between-group differences were detected (all p < 0.05). The mean CIBIC-Plus values for the AG group at T1 and T2 were much lower than that for the DG group, and there were significant differences between the two groups (푃<0.05). There were no significant between-group differences in the scores of ADAS-ADL23 and NPI during the study period. Treatment discontinuations due to adverse events were 0 (0%) and 4 (9.09%) for the AG and DG groups, respectively. CONCLUSIONS: Acupuncture is safe, well tolerated and effective in improving the cognitive function, global clinical status of AD. TRIAL REGISTRATION: ChiCTR-IOR-17010465 (Retroactively registered on 18 JAN 2017).

[Acupuncture Regulated the Expressions of Hsp84 and Hsp86 and Postponed Brain Aging in SAMP8].

Objective To observe the correlations between heat shock protein 84 ( Hsp84)/ Hsp86 and brain aging in senescence accelerated mouse prone 8 (SAMP8) and the regulation effects of acupuncture. Methods Ten senescence accelerated mouse resistant 1 (SAMR1) were recruited as a normal control group. Another 30 SAMP8 mice were divided into the blank control group, the acupuncture group, and the non-acupoint group by random digit table, 10 in each group. Mice in the acupuncture group received treatment with "Sanjiao" acupuncture method. Mice in the non-acupoint group were needled at two fixed non-acupoints located at bilateral hypochondrium of the body. Catching stimulus at equal volume was given to mice in the rest two groups. All intervention was performed once per day for 15 successive days. Neuromuscular coordination of mice was evaluated. Levels of oxidative stress and protein carbonyl were determined. mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus of mice and Neuro-2a cells were detected using Real-time PCR and Western blot. Results Compared with the normal control group, the success rate of tight rope experiment was lowered (P <0. 01) , levels of super- oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the hippocampus were reduced (P < 0. 01) , the levels of superoxide anion and protein carbonyl increased (P <0. 01, P <0. 05), mRNA and protein expression levels of Hsp84 and Hsp86 in the hippocampus decreased (P <0. 01) in the blank con- trol group. Compared with the blank control group and the non-acupoint group, the success rate of tight rope experiment was elevated (P <0. 05) , levels of SOD and GSH-Px were increased (P <0. 05, P < 0. 01) , the levels of superoxide anion and protein carbonyl decreased (P <0. 01 , P <0. 05), and expres- sion levels of Hsp84 and Hsp86 in the hippocampus increased (P <0. 01) in the acupuncture group. mR- NA expression levels of Hsp84 and Hsp86 were decreased in Neuro-2a cells after treated with AP21-35 (P <0. 01). Conclusions Increased oxidative damage of protein and decreased expression levels of Hsp84 and Hsp86 might be partial reasons for resulting in accumulation of denatured protein and brain aging in SAMP8. Acupuncture could delay brain aging by regulating the expressions of Hsp84 and Hsp86.

Cell-free circulating tumor DNA in plasma/serum of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the common type of lung cancer, which is the leading cause of cancer death throughout the world. Most patients were diagnosed too late for curative treatment. So, it is necessary to develop a minimal invasive method to identify NSCLC at an early stage. In recent years, cell-free circulating tumor DNA (ctDNA) has attracted increasing attention as a potential tumor marker for its minimal invasive, convenient, and easily accepted properties. The amount of ctDNA in plasma or serum was significantly higher in NSCLC patients than that in healthy controls or patients with benign diseases. Furthermore, many studies have proved an association among tumor stage, tumor grade, lymph node involvement, the number of metastatic sites, tumor response, survival outcome, and the ctDNA levels. Many genetic changes, such as gene mutation, loss of heterozygosity, microsatellite instability, and gene methylation were also found in ctDNA in NSCLC patients. These findings demonstrated that the ctDNA could serve as a viable tool to monitor NSCLC and prompted us to find more sensitive and specific biomarkers for clinical practice, especially monitor these cases with at least one known gene abnormality. Here, we reviewed the evidence of ctDNA in NSCLC and consider possible future applications in patient management.

Electroacupuncture improves cerebral blood flow and attenuates moderate ischemic injury via Angiotensin II its receptors-mediated mechanism in rats.

BACKGROUND: To investigate the effects and potential mechanism of electroacupuncture intervention on expressions of Angiotensin II and its receptors-mediated signaling pathway in experimentally induced cerebral ischemia. METHODS: Totally 126 male Wistar rats were randomly divided into control group, model group and EA group. The latter two were further divided into ten subgroups (n = 6) following Middle Cerebral Artery Occlusion (MCAO). Changes in regional cerebral blood flow (rCBF) and expressions of Angiotensin II and its receptors (AT1R, AT2R), as well as effector proteins in phosphatidyl inositol signal pathway were monitored before and at different times after MCAO. RESULTS: MCAO-induced decline of ipsilateral rCBF was partially suppressed by electroacupuncture, and contralateral blood flow was also superior to that of model group. Angiotensin II level was remarkably elevated immediately after MCAO, while electroacupuncture group exhibited significantly lower levels at 1 to 3 h and the value was significantly increased thereafter. The enhanced expression of AT1R was partially inhibited by electroacupuncture, while increased AT2R level was further induced. Electroacupuncture stimulation attenuated and postponed the upregulated-expressions of Gq and CaM these upregulations. ELISA results showed sharply increased expressions of DAG and IP3, which were remarkably neutralized by electroacupuncture. CONCLUSIONS: MCAO induced significant increases in expression of Angiotensin II and its receptor-mediated signal pathway. These enhanced expressions were significantly attenuated by electroacupuncture intervention, followed by reduced vasoconstriction and improved blood supply in ischemic region, and ultimately conferred beneficial effects on cerebral ischemia.

Development of a PET scanner for simultaneously imaging small animals with MRI and PET.

Recently, positron emission tomography (PET) is playing an increasingly important role in the diagnosis and staging of cancer. Combined PET and X-ray computed tomography (PET-CT) scanners are now the modality of choice in cancer treatment planning. More recently, the combination of PET and magnetic resonance imaging (MRI) is being explored in many sites. Combining PET and MRI has presented many challenges since the photo-multiplier tubes (PMT) in PET do not function in high magnetic fields, and conventional PET detectors distort MRI images. Solid state light sensors like avalanche photo-diodes (APDs) and more recently silicon photo-multipliers (SiPMs) are much less sensitive to magnetic fields thus easing the compatibility issues. This paper presents the results of a group of Canadian scientists who are developing a PET detector ring which fits inside a high field small animal MRI scanner with the goal of providing simultaneous PET and MRI images of small rodents used in pre-clinical medical research. We discuss the evolution of both the crystal blocks (which detect annihilation photons from positron decay) and the SiPM array performance in the last four years which together combine to deliver significant system performance in terms of speed, energy and timing resolution.

[Effect of acupuncture on transmembrane signal pathway in AD mice: an analysis based on lipid-raft proteomics].

OBJECTIVE: To reveal the transmembrane signal pathway participating in regulating neuron functions of treating Alzheimer's disease (AD) by acupuncture. METHODS: SAMP8 mice was used for AD animal model. The effect of acupuncture method for qi benefiting, blood regulating, health supporting, and root strengthening on the amount and varieties of transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice was detected using HPLC MS/MS proteomics method. RESULTS: Compared with the control group, acupuncture increased 39 transmembrane signal proteins from hippocampal lipid rafts in SAMP8 mice, of them, 14 belonged to ionophorous protein, 8 to G protein, 8 to transmembrane signal receptor, and 9 to kinase protein. Totally 3 main cell signal pathways were involved, including G-protein-coupled receptors signal, enzyme linked receptor signal, and ion-channel mediated signal. Compared with the sham-acupuncture group, acupuncture resulted in significant increase of kinase signal protein amount. From the aspect of functions, they were dominant in regulating synapse functions relevant to cytoskeleton and secreting neurotransmitters. CONCLUSION: The cell biological mechanism for treating AD by acupuncture might be achieved by improving synapse functions and promoting the secretion of neurotransmitters through transmembrane signal transduction, thus improving cognitive function of AD patients.

Hippocampal neuron loss is correlated with cognitive deficits in SAMP8 mice.

The objective of this study is to examine whether neuron loss occurs in SAMP8 and whether neuron loss is correlated with cognitive deficits of these mice. Neuronal loss is considered as one of the most important pathological hallmarks of Alzheimer disease (AD). In addition to the early-onset, irreversible, severe deficits of learning and memory, SAMP8 mice show spontaneous age-related neurodegenerative changes and other characteristics seen in AD patients, such as amyloid plaques and neurofibrillary tangles. However, it is still unknown whether neuron loss occurs in SAMP8 and whether neuron loss is correlated with cognitive deficits of these mice. We employed 8-month-old SAMP8 and SAMR1 mice to investigate the cognitive function and neuron numbers. The behaviors were examined by the grading score of senescence and Morris water maze (MWM) test, the neuron number in hippocampus was estimated by the optical fractionator technique. The grading score of senescence and MWM test demonstrated that SAMP8 exhibited notable age-related changes in appearance and cognitive function. Moreover, severe hippocampal neuron loss was found in SAMP8 as determined by the optical fractionator stereological method. Compared to SAMR1, the neuron number of CA1, CA3 and DG in SAMP8 was reduced by 15.6, 19.8 and 20.2 %, respectively, and the neuron loss in hippocampus was associated with cognitive deficits. Collectively, these results suggest that hippocampal neuronal loss is well correlated with learning and memory deficits in SAMP8 and SAMP8 represents an important mouse model for AD.

Age-related alteration in cerebral blood flow and energy failure is correlated with cognitive impairment in the senescence-accelerated prone mouse strain 8 (SAMP8).

Cerebrovascular dysfunction is an early pathogenic event in Alzheimer's disease (AD) and plays a key role in the disease process. Cerebral hypoperfusion, brain glucose hypometabolism and disrupted blood-brain barrier (BBB) integrity contributed to the onset and progression of AD. However, the relationships between the age-related cognitive impairment and cerebral blood flow (CBF), energy metabolism and BBB have not been clearly explained. In this study, we investigated the cognitive function, CBF, BBB damage and expression level of glucose transporter (GLUT) 1 and 3 of senescence-accelerated mouse prone 8 (SAMP8), and the correlations between each of them were analyzed. When compared with SAMR1 (senescence-accelerated mouse resistant 1), the cognitive abilities of SAMP8 were damaged apparently even at 4 months of age, showing up a slower and more capricious acquisition in Morris water maze tasks. In both SAMP8 and SAMR1, reduced CBF and increased BBB leakage were observed with increasing age, but an earlier and more severe impairment was detected in SAMP8. In addition, alterations of GLUT1 and GLUT3 protein expression in cortex and hippocampus were more prominent in SAMP8. Correlation analysis demonstrated that the increased escape latency was correlated negatively with CBF and expression of glucose transporters; and positively with BBB permeability in the hippocampus. These results suggested that CBF, BBB integrity, the expression of GLUT1 and GLUT3 were significantly affected by age and strain, which were also closely associated with cognitive ability. The alteration in CBF and energy failure induced by aging and vascular insults resulted in cognitive decline in SAMP8.

[Effect of acupuncture on the p53 protein expression of mice with Alzheimer's disease].

OBJECTIVE: To observe the effect of acupuncture method for benefiting qi, regulating blood, supplementing the root, and cultivating the essence (BQRBSRCE) on the p53 protein expression of mice with Alzheimer's disease (AD). METHODS: SAMP8 mice were divided into the control group, the acupuncture group, and the non-acupoint group. The homologous SAMR1 control group was set up. Mice in the acupuncture group used acupuncture method for BQRBSRCE by needling at Tanzhong (RN17), Zhongwan (RN12), Qihai (RN6), and bilateral Xuehai (SP10), and bilateral Zusanli (ST36).Two fixed non-acupoints from bilateral ribs were needled in the non-acupoint group. The p53 protein expression in the cortex and hippocampus of mice was determined using Western blot. The pathological changes of neurons in the hippocampal CA1 region, the temporal lobe, and the occipital lobe were observed using HE staining. The expression of cortical p53-positive cells was detected by immunohistochemical assay. RESULTS: The p53 protein was highly expressed in the cortex of SAMP8, which was significantly down-regulated after acupuncture, showing statistical difference when compared with the SAMP8 control group (P < 0.05), but with no statistical difference when compared with the SAMR1 control group (P > 0.05). Needling at non-acupoints had no obvious effect on the p53 protein expression. There was no statistical difference in the p53 protein expression of the hippocampus (P > 0.05). CONCLUSION: Acupuncture method for BQRBSRCE could down-regulate the p53 protein expression in the brain of mice, improve the pathological state of brain cells, thus enhancing learning and memory capabilities of AD mice, improving their cognitive functions, with specificity of acupoints.

Multimodality neuroimaging in vascular mild cognitive impairment: A narrative review of current evidence.

The vascular mild cognitive impairment (VaMCI) is generally accepted as the premonition stage of vascular dementia (VaD). However, most studies are focused mainly on VaD as a diagnosis in patients, thus neglecting the VaMCI stage. VaMCI stage, though, is easily diagnosed by vascular injuries and represents a high-risk period for the future decline of patients' cognitive functions. The existing studies in China and abroad have found that magnetic resonance imaging technology can provide imaging markers related to the occurrence and development of VaMCI, which is an important tool for detecting the changes in microstructure and function of VaMCI patients. Nevertheless, most of the existing studies evaluate the information of a single modal image. Due to the different imaging principles, the data provided by a single modal image are limited. In contrast, multi-modal magnetic resonance imaging research can provide multiple comprehensive data such as tissue anatomy and function. Here, a narrative review of published articles on multimodality neuroimaging in VaMCI diagnosis was conducted，and the utilization of certain neuroimaging bio-markers in clinical applications was narrated. These markers include evaluation of vascular dysfunction before tissue damages and quantification of the extent of network connectivity disruption. We further provide recommendations for early detection, progress, prompt treatment response of VaMCI, as well as optimization of the personalized treatment plan.

Effect of Huangdisan grain on improving cognitive impairment in VD rats and its mechanism in immune inflammatory response.

BACKGROUND: Vascular dementia (VD) is the second most common type of dementia after Alzheimer's disease (AD). Although the incidence rate is very high, there is no definitive treatment for VD. And it has serious impact on the quality of life of VD patients. In recent years, more and more studies about the clinical efficacy and pharmacological effects of traditional Chinese medicine (TCM) in the treatment of VD have been conducted. And Huangdisan grain has been used to treat VD patients with a good curative effect in clinic. OBJECTIVE: This study was designed to investigate the effect of Huangdisan grain on the inflammatory response and cognitive function of VD rats modeled by bilateral common carotid artery occlusion (BCCAO), that aimed to improve the treatment methods for VD. METHODS: 8-week-old healthy SPF male Wistar rats (280 ± 20 g) were randomly divided into the normal group (Gn, n = 10), sham operated group (Gs, n = 10), and operated group (Go, n = 35). The VD rat models in Go group were established by BCCAO. 8 weeks after surgery, the operated rats were screened by the hidden platform trail of Morris Water Maze (MWM), and the rats with cognitive dysfunction were further randomly divided into the impaired group (Gi, n = 10) and TCM group (Gm, n = 10). The VD rats in Gm group were given the intragastric administration of Huangdisan grain decoction once a day for 8 weeks, and the other groups were given intragastric administration of normal saline. Then the cognitive ability of rats in each group was detected by the MWM Test. The lymphocyte subsets in peripheral blood and hippocampus of rats were measured by flow cytometry. The levels of cytokines (IL-1ß, IL-2, IL-4, IL-10, TNF-α, INF-γ, MIP-2, COX-2, iNOS) in peripheral blood and hippocampus were measured by ELISA (enzyme linked immunosorbent assay). The number of Iba-1+ CD68+ co-positive cells in the CA1 region of hippocampus was measured by immunofluorescence. RESULTS: Compared with the Gn group, the escape latencies of the Gi group were prolonged (P < 0.01), the time spent in the former platform quadrant was shortened (P < 0.01), and the number of times of crossing over the former platform location was reduced (P < 0.05). But compared with the Gi group, the escape latencies of Gm group were shortened (P < 0.01), the time spent in the former platform quadrant was prolonged (P < 0.05), and the number of times of crossing over the former platform location was increased (P < 0.05). The number of Iba-1+ CD68+ co-positive cells in the CA1 region of hippocampus of VD rats in Gi group was increased (P < 0.01) compared with the Gn group. And the proportions of T Cells, CD4+ T Cells, CD8+ T Cells in the hippocampus were increased (P < 0.01). The level of pro-inflammatory cytokines in the hippocampus was increased significantly, such as IL-1ß (P < 0.01), IL-2 (P < 0.01), TNF-α (P < 0.05), IFN-γ (P < 0.01), COX-2 (P < 0.01), MIP-2 (P < 0.01) and iNOS (P < 0.05). And the level of IL-10 (P < 0.01), a kind of anti-inflammatory cytokine, was decreased. The proportions of T Cells (P < 0.05), CD4+ T Cells (P < 0.01) and NK Cells (P < 0.05) in the peripheral blood of the VD rats in Gi group were decreased, and the level of IL-1ß, IL-2, TNF-α, IFN-γ, COX-2, MIP-2 and iNOS was increased significantly (P < 0.01) compared with the Gn group. Meanwhile, the level of IL-4 and IL-10 was decreased (P < 0.01). Huangdisan grain could reduce the number of Iba-1+ CD68+ co-positive cells in the CA1 region of hippocampus (P < 0.01), decrease the proportions of T Cells, CD4+ T Cells, CD8+ T Cells and the level of IL-1ß, MIP-2 in hippocampus (P < 0.01) of VD rats. Moreover, it could rise the proportion of NK Cells (P < 0.01) and the level of IL-4 (P < 0.05), IL-10 (P < 0.05), and decrease the level of IL-1ß (P < 0.01), IL-2 (P < 0.05), TNF-α (P < 0.01), IFN-γ (P < 0.01), COX-2 (P < 0.01) and MIP-2 (P < 0.01) in peripheral blood of VD rats. CONCLUSION: This study indicated that Huangdisan grain could decrease the activation of microglia/macrophages, regulate the proportions of lymphocyte subsets and the level of cytokines, which could adjust the immunologic abnormalities of VD rats, and ultimately improve cognitive function.

Molecular Mechanism of Electroacupuncture Regulating Cerebral Arterial Contractile Protein in Rats with Cerebral Infarction Based on MLCK Pathway.

OBJECTIVE: To explore the effect of electroacupuncture (EA) intervention on the vasoconstriction of cerebral artery smooth muscle cells after cerebral infarction. METHODS: Male Wistar rats were randomly divided into 3 groups by a random number table: the model group (n=24), the EA group (n=24), and the normal group (n=6). The model and the EA groups were divided into different time subgroups at 0.5, 1, 3, and 6 h after middle cerebral artery occlusion (MCAO), with 6 rats in each subgroup. MCAO model was established using intraluminal suture occlusion method. The EA group was given EA treatment at acupoint Shuigou (GV 26) instantly after MCAO for 20 min. The contents of cerebrovascular smooth muscle MLCK, the 3 subunits of myosin light chain phosphatase (MLCP) MYPT1, PP1c-δ and M20, as well as myosin-ATPase activity were detected using immunohistochemistry and Western blotting. RESULTS: The overall expression level of the MYPT1 and PP1c-δ in the model group was significantly higher (P<0.01). After EA intervention, the 0.5 h group expression level was close to that of the normal group (P>0.05), and the other subgroups were still significantly higher than the normal group (P<0.01). After EA intervention, the expression level of each subgroup was significantly lower than the corresponding model group. There was a significant difference between the 0.5 and 1 h subgroups (P<0.01), while a difference was also observed between the 3 and 6 h subgroups (P<0.05). The dynamic change rule gradually increased with the prolongation of infarction time within 6 h after infarction. CONCLUSION: EA intervention can inhibit contraction of cerebral vascular smooth muscle cells and regulate smooth muscle relaxation by regulating MLCK pathway.

Efficacy of acupuncture and pharmacological therapies for vascular cognitive impairment with no dementia: a network meta-analysis.

Background and objective: Vascular cognitive impairment with no dementia (VCIND) is considered to be the prodromal stage of vascular dementia, characterized by insidious onset. Although acupuncture and drug therapies are effective, the optimal therapy for VCIND remains to be further determined. Therefore, we conducted a network meta-analysis to compare the effectiveness of acupuncture therapies and current common medicines for VCIND. Methods: We searched eight electronic databases to identify eligible randomized controlled trials of patients with VCIND treated by acupuncture or drug therapies. The primary outcome was Montreal Cognitive Assessment, and the secondary outcome was Mini-Mental State Examination. We conducted the network meta-analysis within a Bayesian framework. Weighted mean difference with 95% confidence intervals were applied as effect sizes to continuous data for all outcomes. Sensitivity analysis was done to assess the robustness of the findings, and we also carried out a subgroup analysis based on age. We assessed the risk of bias using the Risk of Bias 2.0 tool and applied the Grade of Recommendation Assessment, Development and Evaluation (GRADE) to assess the quality of the outcomes. This study was registered with PROSPERO, number CRD42022331718. Results: A total of 33 studies with 14 interventions were included, including 2603 participants. In terms of the primary outcome, manual acupuncture plus herbal decoction was considered to be the most effective intervention (P = 91.41%), followed by electroacupuncture (P = 60.77%) and manual acupuncture plus piracetam (P = 42.58%), whereas donepezil hydrochloride ranked the least efficacious intervention (P = 54.19%). For the secondary outcome, electroacupuncture plus nimodipine was considered to be the most effective intervention (P = 42.70%), followed by manual acupuncture plus nimodipine (P = 30.62%) and manual acupuncture (P = 28.89%), whereas nimodipine ranked the least efficacious intervention (P = 44.56%). Conclusion: Manual acupuncture plus herbal decoction might be the most effective intervention for VCIND. The combination of acupuncture and drug therapy had a tendency to perform better than monotherapy in terms of clinical outcomes. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=331718, identifier: CRD42022331718.

[Acupuncture for improving neuroinflammation in vascular dementia rats by regulating Th1/Th2 cells balance in peripheral blood].

OBJECTIVE: To observe the effect of acupuncture on the balance of T helper (Th) 1/Th2 cells in peripheral blood, inflammatory reaction and intracerebral neuroinflammation in vascular dementia (VD) rats, and to explore the mechanism of acupuncture for improving cognitive function in VD. METHODS: A total of 60 SPF Wistar rats were randomized into a normal group (n=12), a sham operation group (n=12) and an operation group (n=36). Bilateral common carotid artery occlusion was adopted to establish the VD model in rats of the operation group. The rats of successful modeling were randomized into a model group and an acupuncture group, 12 rats in each one. In the acupuncture group, Sanjiao acupuncture was applied at "Danzhong" (CV 17), "Zhongwan" (CV 12), "Qihai" (CV 6), "Xuehai" (SP 10) and "Zusanli" (ST 36), the needles were manipulated for 30 s at each acupoint, without retaining. The intervention was given once a day for 15 days, and there was 1-day rest on day 8. Morris water maze test was adopted to observe the ethology, flow cytometry was used to detect the ratio of Th1/Th2 in peripheral blood, and Luminex liquid chip technology was used to detect the levels of interleukin (IL)-4, IL-10, interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in serum and hippocampus. RESULTS: There were no significant differences in various indexes between the normal group and the sham operation group (P>0.05). Compared with the sham operation group, in the model group, the escape latency of hidden platform test and reversal platform test was prolonged (P<0.01), the residence time of the original platform quadrant was shortened and the number of crossing the original platform was reduced in probe test (P<0.01, P<0.05), the proportion of Th1 cells was increased, the proportion of Th2 cells was decreased and the ratio of Th1/Th2 cells was increased in peripheral blood (P<0.01), the levels of TNF-α and IFN-γ were increased, the levels of IL-4 and IL-10 were decreased in serum and hippocampus (P<0.05, P<0.01). Compared with the model group, in the acupuncture group, the escape latency of hidden platform test and reversal platform test was shortened (P<0.01), the residence time of the original platform quadrant of the probe test was prolonged (P<0.05), the proportion of Th1 cells was decreased, the proportion of Th2 cells was increased and the ratio of Th1 / Th2 cells was decreased in peripheral blood (P<0.05), the levels of TNF-α and IFN-γ were decreased, the levels of IL-4 and IL-10 were increased in serum and hippocampus (P<0.05, P<0.01). CONCLUSION: Acupuncture can improve the cognitive dysfunction and reduce the intracerebral neuroinflammation in VD rats, its mechanism may relate to the regulation of Th1/Th2 cells balance and reduce the inflammatory reaction in peripheral blood.