Fractional amplitude of low-frequency fluctuation and voxel-mirrored homotopic connectivity in patients with persistent postural-perceptual dizziness: resting-state functional magnetic resonance imaging study.

PURPOSE: Persistent postural-perception dizziness (PPPD) is a chronic subjective form of dizziness characterized by the exacerbation of dizziness with active or passive movement, complex visual stimuli, and upright posture. Therefore, we aimed to analyze the resting-state functional magnetic resonance imaging (fMRI) in patients with PPPD using fractional amplitude of low-frequency fluctuation (fALFF) and voxel-mirrored homotopic connectivity (VMHC) and evaluate the correlation between abnormal regions in the brain and clinical features to investigate the pathogenesis of PPPD. METHODS: Thirty patients with PPPD (19 females and 11 males) and 30 healthy controls (HC) (18 females and 12 males) were closely matched for age and sex. The fALFF and VMHC methods were used to investigate differences in fMRI (BOLD sequences) between the PPPD and HC groups and to explore the associations between areas of functional abnormality and clinical characteristics (Dizziness, Anxiety, Depression, and Duration). RESULT: Compared to the HC group, patients with PPPD displayed different functional change patterns, with increased fALFF in the right precuneus and decreased VMHC in the bilateral precuneus. Additionally, patients with PPPD had a positive correlation between precuneus fALFF values and dizziness handicap inventory (DHI) scores, and a negative correlation between VMHC values and the disease duration. CONCLUSIONS: Precuneus dysfunction was observed in patients with PPPD. The fALFF values correlated with the degree of dizziness in PPPD, and changes in VMHC values were associated with the duration of dizziness, suggesting that fMRI changes in the precuneus of patients could be used as a potential imaging marker for PPPD.

Increased functional connectivity between default mode network and visual network potentially correlates with duration of residual dizziness in patients with benign paroxysmal positional vertigo.

Objective: To assess changes in static and dynamic functional network connectivity (sFNC and dFNC) and explore their correlations with clinical features in benign paroxysmal positional vertigo (BPPV) patients with residual dizziness (RD) after successful canalith repositioning maneuvers (CRM) using resting-state fMRI. Methods: We studied resting-state fMRI data from 39 BPPV patients with RD compared to 38 BPPV patients without RD after successful CRM. Independent component analysis and methods of sliding window and k-means clustering were adopted to investigate the changes in dFNC and sFNC between the two groups. Additionally, temporal features and meta-states were compared between the two groups. Furthermore, the associations between fMRI results and clinical characteristics were analyzed using Pearson's partial correlation analysis. Results: Compared with BPPV patients without RD, patients with RD had longer duration of BPPV and higher scores of dizziness handicap inventory (DHI) before successful CRM. BPPV patients with RD displayed no obvious abnormal sFNC compared to patients without RD. In the dFNC analysis, patients with RD showed increased FNC between default mode network (DMN) and visual network (VN) in state 4, the FNC between DMN and VN was positively correlated with the duration of RD. Furthermore, we found increased mean dwell time (MDT) and fractional windows (FW) in state 1 but decreased MDT and FW in state 3 in BPPV patients with RD. The FW of state 1 was positively correlated with DHI score before CRM, the MDT and FW of state 3 were negatively correlated with the duration of BPPV before CRM in patients with RD. Additionally, compared with patients without RD, patients with RD showed decreased number of states and state span. Conclusion: The occurrence of RD might be associated with increased FNC between DMN and VN, and the increased FNC between DMN and VN might potentially correlate with the duration of RD symptoms. In addition, we found BPPV patients with RD showed altered global meta-states and temporal features. These findings are helpful for us to better understand the underlying neural mechanisms of RD and potentially contribute to intervention development for BPPV patients with RD.

Altered parietal operculum cortex 2 functional connectivity in benign paroxysmal positional vertigo patients with residual dizziness: A resting-state fMRI study.

AIMS: To investigate changes in functional connectivity (FC) focusing on parietal operculum cortex 2 (OP2) in benign paroxysmal positional vertigo (BPPV) patients with residual dizziness (RD) after successful canalith repositioning procedure (CRP). METHODS: High-resolution three-dimensional T1 and resting-state functional magnetic resonance imaging (fMRI) were performed on 55 healthy controls (HCs), 55 BPPV patients with RD, and 55 patients without RD after successful CRP. Seed-based (bilateral OP2) FC was calculated to investigate the changes in FC among the three groups. Additionally, we further explored the associations between abnormal FC and clinical symptoms. RESULTS: One-way analysis of covariance showed significant FC differences among the three groups. Post-hoc analysis showed that patients with RD exhibited decreased FC between left OP2 and regions of left angular gyrus (AG), thalamus, precuneus, middle frontal gyrus (MFG), and right cerebellum posterior lobe (CPL) in comparison with HCs. In addition, compared with patients without RD, patients with RD showed decreased FC between left OP2 and regions of left MFG, AG, middle temporal gyrus, and right CPL. Moreover, in patients with RD, the FC between left thalamus and OP2 was negatively correlated with duration of RD, and the FC between left AG and OP2 was negatively correlated with duration of BPPV. CONCLUSION: BPPV patients with RD showed reduced FC between brain regions involved in vestibular processing and spatial cognition; These results suggested that BPPV patients with RD might have diminished central processing of vestibular information and impaired spatial cognition.

A clinical prediction model based on interpretable machine learning algorithms for prolonged hospital stay in acute ischemic stroke patients: a real-world study.

Objective: Acute ischemic stroke (AIS) brings an increasingly heavier economic burden nowadays. Prolonged length of stay (LOS) is a vital factor in healthcare expenditures. The aim of this study was to predict prolonged LOS in AIS patients based on an interpretable machine learning algorithm. Methods: We enrolled AIS patients in our hospital from August 2017 to July 2019, and divided them into the "prolonged LOS" group and the "no prolonged LOS" group. Prolonged LOS was defined as hospitalization for more than 7 days. The least absolute shrinkage and selection operator (LASSO) regression was applied to reduce the dimensionality of the data. We compared the predictive capacity of extended LOS in eight different machine learning algorithms. SHapley Additive exPlanations (SHAP) values were used to interpret the outcome, and the most optimal model was assessed by discrimination, calibration, and clinical utility. Results: Prolonged LOS developed in 149 (22.0%) of the 677 eligible patients. In eight machine learning algorithms, prolonged LOS was best predicted by the Gaussian naive Bayes (GNB) model, which had a striking area under the curve (AUC) of 0.878 ± 0.007 in the training set and 0.857 ± 0.039 in the validation set. The variables sorted by the gap values showed that the strongest predictors were pneumonia, dysphagia, thrombectomy, and stroke severity. High net benefits were observed at 0%-76% threshold probabilities, while good agreement was found between the observed and predicted probabilities. Conclusions: The model using the GNB algorithm proved excellent for predicting prolonged LOS in AIS patients. This simple model of prolonged hospitalization could help adjust policies and better utilize resources.

Altered functional activity of the precuneus and superior temporal gyrus in patients with residual dizziness caused by benign paroxysmal positional vertigo.

Objective: Benign paroxysmal positional vertigo (BPPV) is a common clinical vertigo disease, and the most effective treatment for this disease is canal repositioning procedures (CRP). Most patients return to normal after a single treatment. However, some patients still experience residual dizziness (RD) after treatment, and this disease's pathogenesis is currently unclear. The purpose of this study is to explore whether there are abnormal brain functional activities in patients with RD by using resting-state functional magnetic resonance imaging (rs-fMRI) and to provide imaging evidence for the study of the pathogenesis of RD. Materials and methods: The BPPV patients in the Second Affiliated Hospital of Xuzhou Medical University had been included from December 2021 to November 2022. All patients had been received the collection of demographic and clinical characteristics (age, gender, involved semicircular canal, affected side, CRP times, BPPV course, duration of RD symptoms, and whether they had hypertension, diabetes, coronary heart disease.), scale assessment, including Dizziness Handicap Inventory (DHI), Hamilton Anxiety Inventory (HAMA), Hamilton Depression Inventory (HAMD), rs-fMRI data collection, CRP treatment, and then a one-month follow-up. According to the follow-up results, 18 patients with RD were included. At the same time, we selected 19 healthy individuals from our hospital's physical examination center who matched their age, gender as health controls (HC). First, the amplitude of low-frequency fluctuations (ALFF) analysis method was used to compare the local functional activities of the two groups of subjects. Then, the brain regions with different ALFF results were extracted as seed points. Functional connectivity (FC) analysis method based on seed points was used to explore the whole brain FC of patients with RD. Finally, a correlation analysis between clinical features and rs-fMRI data was performed. Results: Compared to the HC, patients with RD showed lower ALFF value in the right precuneus and higher ALFF value in the right superior temporal gyrus (STG). When using the right STG as a seed point, it was found that the FC between the right STG, the right supramarginal gyrus (SMG), and the left precuneus was decreased in RD patients. However, no significant abnormalities in the FC were observed when using the right precuneus as a seed point. Conclusion: In patients with RD, the local functional activity of the right precuneus is weakened, and the local functional activity of the right STG is enhanced. Furthermore, the FC between the right STG, the right SMG, and the left precuneus is weakened. These changes may explain the symptoms of dizziness, floating sensation, walking instability, neck tightness, and other symptoms in patients with RD to a certain extent.

Development and validation of a machine learning-based prognostic risk stratification model for acute ischemic stroke.

Acute ischemic stroke (AIS) is a most prevalent cause of serious long-term disability worldwide. Accurate prediction of stroke prognosis is highly valuable for effective intervention and treatment. As such, the present retrospective study aims to provide a reliable machine learning-based model for prognosis prediction in AIS patients. Data from AIS patients were collected retrospectively from the Second Affiliated Hospital of Xuzhou Medical University between August 2017 and July 2019. Independent prognostic factors were identified by univariate and multivariate logistic analysis and used to develop machine learning (ML) models. The ML model performance was assessed by area under the receiver operating characteristic curve (AUC) and radar plot. Shapley Additive explanations (SHAP) values were used to interpret the importance of all features included in the predictive model. A total of 677 AIS patients were included in the present study. Poor prognosis was observed in 209 patients (30.9%). Six variables, including neuron specific enolase (NSE), homocysteine (HCY), S-100ß, dysphagia, C-reactive protein (CRP), and anticoagulation were included to establish ML models. Six different ML algorithms were tested, and Random Forest model was selected as the final predictive model with the greatest AUC of 0.908. Moreover, according to SHAP results, NSE impacted the predictive model the most, followed by HCY, S-100ß, dysphagia, CRP and anticoagulation. Based on the RF model, an online tool was constructed to predict the prognosis of AIS patients and assist clinicians in optimizing patient treatment. The present study revealed that NSE, HCY, CRP, S-100ß, anticoagulation, and dysphagia were important factors for poor prognosis in AIS patients. ML algorithms were used to develop predictive models for predicting the prognosis of AIS patients, with the RF model presenting the optimal performance.

Corrigendum: A machine learning model for visualization and dynamic clinical prediction of stroke recurrence in acute ischemic stroke patients: a real-world retrospective study.

[This corrects the article DOI: 10.3389/fnins.2023.1130831.].

A machine learning model for visualization and dynamic clinical prediction of stroke recurrence in acute ischemic stroke patients: A real-world retrospective study.

Background and purpose: Recurrent stroke accounts for 25-30% of all preventable strokes, and this study was conducted to establish a machine learning-based clinical predictive rice idol for predicting stroke recurrence within 1 year in patients with acute ischemic stroke (AIS). Methods: A total of 645 AIS patients at The Second Affiliated Hospital of Xuzhou Medical University were screened, included and followed up for 1 year for comprehensive clinical data. Univariate and multivariate logistic regression (LR) were used to screen the risk factors of stroke recurrence. The data set was randomly divided into training set and test set according to the ratio of 7:3, and the following six prediction models were established by machine algorithm: random forest (RF), Naive Bayes model (NBC), decision tree (DT), extreme gradient boosting (XGB), gradient boosting machine (GBM) and LR. The model with the strongest prediction performance was selected by 10-fold cross-validation and receiver operating characteristic (ROC) curves, and the models were investigated for interpretability by SHAP. Finally, the models were constructed to be visualized using a web calculator. Results: Logistic regression analysis showed that right hemisphere, homocysteine (HCY), C-reactive protein (CRP), and stroke severity (SS) were independent risk factors for the development of stroke recurrence in AIS patients. In 10-fold cross-validation, area under curve (AUC) ranked from 0.777 to 0.959. In ROC curve analysis, AUC ranged from 0.887 to 0.946. RF model has the best ability to predict stroke recurrence, and HCY has the largest contribution to the model. A web-based calculator https://mlmedicine-re-stroke2-re-stroke2-baylee.streamlitapp.com/ has been developed accordingly. Conclusion: This study identified four independent risk factors affecting recurrence within 1 year in stroke patients, and the constructed RF-based prediction model had good performance.

The predictors of death within 1 year in acute ischemic stroke patients based on machine learning.

Objective: To explore the predictors of death in acute ischemic stroke (AIS) patients within 1 year based on machine learning (ML) algorithms. Methods: This study retrospectively analyzed the clinical data of patients hospitalized and diagnosed with AIS in the Second Affiliated Hospital of Xuzhou Medical University between August 2017 and July 2019. The patients were randomly divided into training and validation sets at a ratio of 7:3, and the clinical characteristic variables of the patients were screened using univariate and multivariate logistics regression. Six ML algorithms, including logistic regression (LR), gradient boosting machine (GBM), extreme gradient boosting (XGB), random forest (RF), decision tree (DT), and naive Bayes classifier (NBC), were applied to develop models to predict death in AIS patients within 1 year. During training, a 10-fold cross-validation approach was used to validate the training set internally, and the models were interpreted using important ranking and the SHapley Additive exPlanations (SHAP) principle. The validation set was used to externally validate the models. Ultimately, the highest-performing model was selected to build a web-based calculator. Results: Multivariate logistic regression analysis revealed that C-reactive protein (CRP), homocysteine (HCY) levels, stroke severity (SS), and the number of stroke lesions (NOS) were independent risk factors for death within 1 year in patients with AIS. The area under the curve value of the XGB model was 0.846, which was the highest among the six ML algorithms. Therefore, we built an ML network calculator (https://mlmedicine-de-stroke-de-stroke-m5pijk.streamlitapp.com/) based on XGB to predict death in AIS patients within 1 year. Conclusions: The network calculator based on the XGB model developed in this study can help clinicians make more personalized and rational clinical decisions.

Aberrant dynamic functional network connectivity in vestibular migraine patients without peripheral vestibular lesion.

PURPOSE: This study aimed to investigate changes in dynamic functional network connectivity (FNC) in patients with vestibular migraine (VM) and explore their relationship with clinical manifestations. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were scanned from 35 VM patients without peripheral vestibular lesion and 40 age-, sex- and education-matched healthy controls (HC). Independent component analysis (ICA), sliding window (SW) and k-means clustering analysis were performed to explore the difference in FNC and temporal characteristics between two groups. Additionally, Pearson's partial correlation analysis was adopted to investigate the relationship between clinical manifestations and rs-fMRI results in patients with VM. RESULTS: Compared with HC, patients with VM showed increased FNC in pairs of extrastriate visual network (eVN)-ventral attention network (VAN), eVN-default mode network (DMN) and eVN-left frontoparietal network (lFPN), and exhibited decreased FNC in pairs of VAN-auditory network (AuN). The altered FNC was correlated with clinical manifestations of patients with VM. Additionally, we found increased mean dwell time and fractional windows in state 2 in VM patients compared with HC. Mean dwell time was positively correlated with headache impact test-6 (HIT-6) scores, fractional windows was positively associated with dizziness handicap inventory (DHI) scores. CONCLUSION: Our results indicated that patients with VM showed altered FNC primarily between sensory networks and networks related to cognitive, emotional and attention implementation, with more time spent in a state characterized by positive FNC between sensor cortex system and dorsal attention network (DAN). These findings could help reinforce the understanding on the neural mechanisms of VM.

Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke.

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357-395 of C X3 C motif chemokine ligand 1 (CX3CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3CL1 (comprising amino acids 357-395 of CX3CL1) disrupts the interaction between postsynaptic density-93 and CX3CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3CL1 (357-395aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3CL1. Furthermore, the a disintegrin and metalloprotease domain 17 (ADAM17) inhibitor GW280264x, which inhibits metalloprotease activity and prevents CX3CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3CL1 formation. Additionally, Tat-CX3CL1 (357-395aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31-34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3CL1 (357-395aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3CL1 (357-395aa) is a potential therapeutic agent for ischemic stroke.

Altered brain function in patients with vestibular migraine: a study on resting state functional connectivity.

PURPOSE: To characterize the altered brain function in patients with vestibular migraine (VM) using resting-state functional magnetic resonance imaging (fMRI). METHODS: In this prospective study, fMRI images as well as clinical characteristics and behavioral scales were collected from 40 VM patients and 40 healthy controls (HC). All patients received neurological, neuro-otological, and conventional MRI examinations to exclude peripheral vestibular lesions, focal lesions, and other neurological diseases. Seed-based (bilateral parietal operculum cortex 2, OP2) functional connectivity (FC) and independent component analysis (ICA)-based functional network connectivity (FNC) were performed to investigate the brain functional changes in patients with VM. Additionally, the correlations between the altered FC/FNC and behavioral results were analyzed. RESULTS: Compared with HC, patients with VM showed increased FC between the left OP2 and right precuneus and exhibited decreased FC between the left OP2 and left anterior cingulate cortex. We also observed increased FC between the right OP2 and regions of the right middle frontal gyrus and bilateral precuneus, as well as decreased FC between the bilateral OP2. Furthermore, patients with VM showed decreased FNC between visual network (VN) and networks of auditory and default mode, and exhibited increased FNC between VN and executive control network. A correlation analysis found that FC between the left OP2 and right precuneus was positively correlated with scores of dizziness handicap inventory (DHI) in patients with VM. CONCLUSION: The present study demonstrated altered brain function in patients with VM.

Analysis of Diagnostic Value of Electrogastrography for Parkinson's Disease and its Predictive Value for the Disease Progression.

The study aimed to evaluate the diagnostic and prognostic value of indexes detected by electrogastrography in Parkinson's disease patients. One hundred twenty early Parkinson's disease patients and 120 healthy controls were recruited, and underwent electrogastrography to detect dominant frequency (DF), instability coefficient of DF (ICDF), low frequency range (LFR), high frequency range (HFR), and normal frequency range (NFR). The receiver operating characteristic (ROC) curve was drawn for the diagnostic value analysis. The motor function was scored with the Unified Parkinson's Disease Rating Scale (UPDRS). Sniffin' Sticks test was used for the olfactory evaluation, and the TDI score consisting of odor threshold (T), odor discrimination (D) and odor identification (I) tests was calculated. The preprandial ICDF of Parkinson's disease patients was significantly higher than that of the control group, and decreased slowly during the late postprandial phase. The levels of LFR%, HFR% and NFR% in Parkinson's disease patients were higher than the control group during both the preprandial and late postprandial phase, and the changes of each index before and after meals were not obvious. Preprandial ICDF value and TDI score had the ability to distinguish Parkinson's disease patients with the AUC of 0.874 and 0.859 respectively. The ICDF detected by electrogastrography has high clinical value in the early diagnosis of Parkinson's disease, and the combination of ICDF and TDI can improve the diagnostic sensitivity and specificity of a single indicator. High ICDF levels during the preprandial phase are related to the poor prognosis of Parkinson's disease patients after treatment.

Early blood pressure changes during systemic thrombolysis and its association with unexplained early neurological deterioration in small subcortical infarct.

Early neurological deterioration (END), observed in the acute phase of small subcortical infarct treated with intravenous thrombolysis (IVT), is not uncommon in these patients. However, in over half of the END cases, the exact cause is yet incompletely understood, which is so-called unexplained END (unEND). Our aim was to investigate the association of early blood pressure (BP) changes with unEND in patients with small subcortical infarct in the perforator territory of middle cerebral artery treated with IVT. Consecutive patients with acute small subcortical infarct treated with IVT were enrolled in this study. unEND was defined as≧2-point increase of NIHSS from baseline to 24 hours, without straightforward causes. BP excursions and BP variability were calculated and compared between patients with unNED and those without. A total of 168 patients with acute small subcortical infarct were included. Of them, there were 29 patients with unEND and 139 without END. During the first 24 hours following IVT, 66 (39.29%) patients had at least one BP excursion. Logistic regression analyses indicated that BP excursion presence (OR = 3.185, 95% CI: 1.238-8.198), SBP excursion presence (OR = 3.535, 95% CI: 1.366-9.143), and number of SBP excursion (OR = 1.466, 95% CI: 1.090-1.973) were independently associated with unEND. Although SBPSD (P < .001) and SBPCV (P < .001) were higher in patients with unEND than those without END, none of the parameters of BP variability predicted unEND in multivariate analyses. BP excursions above guideline thresholds during the first 24 hours following IVT for small subcortical infarct are common and are independently associated with unEND.

The effect of metabolic syndrome and/or hyperglycemia on outcomes of acute ischemic stroke patients treated with intravenous thrombolysis.

BACKGROUNDS AND OBJECTIVES: The impact of metabolic syndrome (MetS)/hyperglycemia on the clinical outcomes of ischemic stroke treated with intravenous thrombolysis (IVT) remains controversial. This study aimed to determine the risks conferred by MetS and hyperglycemia to clinical outcomes in acute ischemic stroke patients treated with IVT. METHOD: Three hundred forty-three ischemic stroke patients treated with IVT were prospective recruited and stratified into four groups: neither, MetS only, hyperglycemia only, or both. The primary outcome was the 3-month poor functional outcome (PFO) which was defined as a 3-month modified Rankin Score (mRS) score ≧3. The secondary outcome included the hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) after IVT. RESULTS: MetS was recognized in 197 (57.43%) patients. During the first 24 h after IVT, 44 (12.83%) patients had HT, of which 17 had sICH. Three-month PFO was found in 98 (28.57%) patients. After adjustment for potential confounders, MetS (odds ratio (OR) = 3.140, 95% confidence interval (CI) = 1.724-5.718) was independently associated with PFO. However, neither MetS nor its components were associated with 24-h HT or sICH. In the further subgroup analysis, we used the "neither" group as reference and found that the presence of both MetS and hyperglycemia (OR = 3.192, 95% CI = 1.338-7.615) and the presence of hyperglycemia only (OR = 2.097, 95% CI = 1.052-4.179) were significantly related to the 3-month PFO. CONCLUSION: MetS is an independent risk factor on 3-month PFO in acute ischemic stroke patients treated with IVT. Compared with "neither," hyperglycemia only or concurrent with MetS was associated with an elevated risk of PFO after receiving IVT.

Tat-SynGAP improves angiogenesis and post-stroke recovery by inhibiting MST1/JNK signaling.

Small G protein Ras induces the activation of apoptosis-related molecule mammalian Ste20-like kinase1 (MST1)/JNK signal pathway, which is involved in the regulation of tissue damage under pathological conditions such as ischemic stroke. Our previous study indicated that GTPase-activating protein for Ras (SynGAP), a negative regulator of Ras, could bind with postsynaptic density protein-93 (PSD-93) and Tat-SynGAP (670-685aa) small peptide to exhibit neuroprotective role. Here, we report that Tat-SynGAP (670-685aa) reduced cerebral edema at acute cerebral ischemia/reperfusion (I/R), improved integrity of blood-brain barrier, and decreased cortical and striatum neuronal injury. Mechanistically, Tat-SynGAP (670-685aa) not only inhibited the phosphorylation of MST1 and JNK and the cleavage of caspase-3, but also facilitated the expression of angiogenesis related molecules VEGF and Ang-1. In conclusion, Tat-SynGAP (670-685aa) reduces neuronal apoptosis and cerebral infarction volume and maintains vascular stability and blood-brain barrier integrity by inhibiting MST1/JNK signaling pathway.

Altered thalamo-cortical functional connectivity in patients with vestibular migraine: a resting-state fMRI study.

PURPOSE: To explore the functional connectivity (FC) between the bilateral thalamus and the other brain regions in patients with vestibular migraine (VM). METHODS: Resting-state fMRI and 3D-T1 data were collected from 37 patients with VM during the interictal period and 44 age-, gender-, and years of education-matched healthy controls (HC). The FC of the bilateral thalamus was analyzed using a standard seed-based whole-brain correlation method. Furthermore, the correlations between thalamus FC and clinical characteristics of patients were investigated using Pearson's partial correlation. RESULTS: Compared with HC, VM patients showed decreased FC between the left thalamus and the left anterior cingulate cortex (ACC), bilateral insular and right supplementary motor cortex. We also observed decreased FC between the right thalamus and the left insular and ACC in VM patients. Furthermore, patients with VM also exhibited increased FC between the left thalamus and the right precuneus and middle frontal gyrus, between the right thalamus and superior parietal lobule. FC between the right thalamus and the left insular was negatively correlated with disease duration (p = 0.019, r = - 0.399), FC between the left thalamus and the left ACC was negatively correlated with HIT-6 score (p = 0.004, r = - 0.484). CONCLUSION: VM patients showed altered FC between thalamus and brain regions involved in pain, vestibular and visual processing, which are associated with specific clinical features. Specifically, VM patients showed reduced thalamo-pain and thallamo-vestibular pathways, while exhibited enhanced thalamo-visual pathway, which provided first insight into the underlying functional brain connectivity in VM patients.

PSD-93 mediates the crosstalk between neuron and microglia and facilitates acute ischemic stroke injury by binding to CX3CL1.

Post-synaptic density 93 (PSD-93) mediates glutamate excitotoxicity induced by ischemic brain injury, which then induces microglial inflammatory response. However, the underlying mechanisms of how PSD-93 mediates the crosstalk between neurons and microglia in the post-synaptic dense region remain elusive. CX3 chemokine ligand 1 (CX3CL1) is a chemokine specifically expressed in neurons while its receptor CX3CR1 is highly expressed in microglia. In this study, we examined the interaction of PSD-93 and CX3CL1 in the crosstalk between neurons and microglia in acute ischemic stroke. We utilized male C57BL/6 mice to establish the middle cerebral artery occlusion model (MCAO) and designed a fusion small peptide Tat-CX3CL1 (357-395aa) to inhibit PSD-93 and CX3CL1 interaction. The combination peaks of PSD-93 and CX3CL1 at 6 hr after I/R were observed. The binding sites were located at the 420-535 amino acid sequence of PSD-93 and 357-395 amino acid sequence of CX3CL1. Tat-CX3CL1 (357-395aa) could inhibit the interaction of PSD-93 and CX3CL1 and inhibited the pro-inflammatory cytokine IL-1ß and TNF-α expression and provided neuroprotection following reperfusion. Together, these data suggest that PSD-93 binds CX3CL1 to activate microglia and initiate neuroinflammation. Specific blockade of PSD-93-CX3CL1 interaction reduces I/R induced neuronal cell death, and provides a new therapeutic target for ischemic stroke.

Butylphthalide soft capsules combined with modified tonic exercise therapy on neurological function and ability of daily living of patients with stroke hemiplegia.

OBJECTIVE: To explore the effect of butylphthalide soft capsules combined with modified tonic exercise therapy on neurologic function and the abilities of daily living in patients with stroke hemiplegia. METHODS: In this retrospective trial, a total of 90 patients with stroke hemiplegia admitted to our hospital from January 2019 to January 2020 were enrolled and divided into a control group and an experimental group according to different treatment methods. The two groups were both treated with butylphthalide soft capsules, and the experimental group was additionally treated by modified tonic exercise therapy. The clinical efficacy, endothelial injury indicators, molecular indicators of oxidative stress, and adverse reactions of the two groups were compared. Generic Quality of Life Inventory-74 (GQOLI-74) was used to assess the quality of life of patients after treatment. The Fugl-Meyer Upper Extremity Assessment (FMA) was used to evaluate their limb function before and after treatment, the National Institute of Health Stroke Scale (NIHSS) was used to evaluate their brain nerve function before and after the treatment, and the activities of daily living (ADL) were employed to assess their activities of daily living before and after treatment. RESULTS: After treatment, the experimental group outperformed the control group in terms of total clinical efficacy (P<0.05). The experimental group had significantly lower endothelial injury indicators and higher molecular indicators of oxidative stress than the control group (all P<0.001). The incidence of adverse reactions in the experimental group was lower than that in the control group (P<0.05). Higher GQOLI-74, FMA, and ADL scores and a significantly lower NIHSS score were obtained in the experimental group than the control group after treatment (P<0.001). CONCLUSION: For patients with stroke hemiplegia, butylphthalide soft capsule combined with modified tonic exercise therapy effectively improves their neurologic function, abilities of daily living, and quality of life.

Analysis of Antiapoptosis Effect of Netrin-1 on Ischemic Stroke and Its Molecular Mechanism under Deleted in Colon Cancer/Extracellular Signal-Regulated Kinase Signaling Pathway.

To analyze the regulatory effect of Netrin-1 in ischemic stroke and its influence on Deleted in Colon Cancer (DCC)/Extracellular Signal-regulated Kinase (ERK) signaling pathway, 20 male rats were selected to construct the rat model of middle cerebral artery occlusion (MCAO), 10 normal rats were selected as healthy controls (Normal Saline (NS)), and they were divided into the MCAO+Netrin-1 group, MCAO group, and NS group according to different treatment schemes. The positive expression of Netrin-1 was detected by immunostaining, magnetic resonance imaging (MRI) was adopted to detect the percentage of rat cerebral infarct volume in the cerebral hemispheres, and Modified Neurological Severity Score (mNSS) was adopted to evaluate postoperative neurological function in rats. Besides, a tunnel staining experiment was applied to detect the apoptosis rate of rat neurons, the sticker removal test was applied to evaluate the postoperative sensory function of rats, and fluorescence staining was adopted to detect the expression of DCC and ERK in rats. The results showed that the percentage of cerebral infarction volume in the cerebral hemispheres of the MCAO+Netrin-1 group was higher than that of the MCAO and NS groups (P < 0.05); in the MCAO+Netrin-1 group, the MCAO mNSS scoring and the time spent in the sticker removal test were lower than the MCAO group (P < 0.05); the apoptosis rate of rats in the MCAO+Netrin-1 group was lower than that in the MCAO group (P < 0.05); the average fluorescence intensity of DCC and p-ERK in the MCAO+Netrin-1 group was higher than that in the MCAO group (P < 0.05); the average fluorescence intensity of p-ERK in the MCAO+Netrin-1 group was higher than that in the MCAO group (P < 0.05). In short, Netrin-1 can effectively reduce the brain tissue damage in rats with ischemic stroke, improve the nerve function and sensory function of rats, and inhibit neuronal cell apoptosis. Netrin-1 can promote DCC expression and ERK phosphorylation, and the EPK signaling pathway may be involved in the antiapoptotic effect of Netrin-1.