Switching of brain networks across different cerebral perfusion states: insights from EEG dynamic microstate analyses.

The alteration of neural interactions across different cerebral perfusion states remains unclear. This study aimed to fulfill this gap by examining the longitudinal brain dynamic information interactions before and after cerebral reperfusion. Electroencephalogram in eyes-closed state at baseline and postoperative 7-d and 3-month follow-ups (moyamoya disease: 20, health controls: 23) were recorded. Dynamic network analyses were focused on the features and networks of electroencephalogram microstates across different microstates and perfusion states. Considering the microstate features, the parameters were disturbed of microstate B, C, and D but preserved of microstate A. The transition probabilities of microstates A-B and B-D were increased to play a complementary role across different perfusion states. Moreover, the microstate variability was decreased, but was significantly improved after cerebral reperfusion. Regarding microstate networks, the functional connectivity strengths were declined, mainly within frontal, parietal, and occipital lobes and between parietal and occipital lobes in different perfusion states, but were ameliorated after cerebral reperfusion. This study elucidates how dynamic interaction patterns of brain neurons change after cerebral reperfusion, which allows for the observation of brain network transitions across various perfusion states in a live clinical setting through direct intervention.

Taurine ameliorates sensorimotor function by inhibiting apoptosis and activating A2 astrocytes in mice after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) is a form of severe acute stroke with very high mortality and disability rates. Early brain injury (EBI) and delayed cerebral ischemia (DCI) contribute to the poor prognosis of patients with SAH. Currently, some researchers have started to focus on changes in amino acid metabolism that occur in brain tissues after SAH. Taurine is a sulfur-containing amino acid that is semi-essential in animals, and it plays important roles in various processes, such as neurodevelopment, osmotic pressure regulation, and membrane stabilization. In acute stroke, such as cerebral hemorrhage, taurine plays a neuroprotective role. However, the role of taurine after subarachnoid hemorrhage has rarely been reported. In the present study, we established a mouse model of SAH. We found that taurine administration effectively improved the sensorimotor function of these mice. In addition, taurine treatment alleviated sensorimotor neuron damage and reduced the proportion of apoptotic cells. Furthermore, taurine treatment enhanced the polarization of astrocytes toward the neuroprotective phenotype while inhibiting their polarization toward the neurotoxic phenotype. This study is the first to reveal the relationship between taurine and astrocyte polarization and may provide a new strategy for SAH research and clinical treatment.

Progress in Multisensory Synergistic Salt Reduction.

Excessive salt intake, primarily from sodium chloride prevalent in modern food processing, poses a significant public health risk associated with hypertension, cardiovascular diseases and stroke. Researchers worldwide are exploring approaches to reduce salt consumption without compromising food flavor. One promising method is to enhance salty taste perception using multisensory synergies, leveraging gustatory, olfactory, auditory, visual, tactile and trigeminal senses to decrease salt intake while preserving food taste. This review provides a comprehensive overview of salt usage in foods, mechanisms of salty taste perception and evaluation methods for saltiness. Various strategies for reducing salt consumption while maintaining food flavor are examined, with existing salt reduction methods' advantages and limitations being critically analyzed. A particular emphasis is placed on exploring the mechanisms and potential of multisensory synergy in salt reduction. Taste interactions, olfactory cues, auditory stimulation, visual appearance and tactile sensations in enhancing saltiness perception are discussed, offering insights into developing nutritious, appealing low-sodium foods. Furthermore, challenges in current research are highlighted, and future directions for effective salt reduction strategies to promote public health are proposed. This review aims to establish a scientific foundation for creating healthier, flavorful low-sodium food options that meet consumer preferences and wellness needs.

Characteristics of saltiness-enhancing peptides derived from yeast proteins and elucidation of their mechanism of action by molecular docking.

This study aimed to identify saltiness-enhancing peptides from yeast protein and elucidate their mechanisms by molecular docking. Yeast protein hydrolysates with optimal saltiness-enhancing effects were prepared under conditions determined using an orthogonal test. Ten saltiness-enhancing peptide candidates were screened using an integrated virtual screening strategy. Sensory evaluation demonstrated that these peptides exhibited diverse taste characteristics (detection thresholds: 0.13-0.50 mmol/L). Peptides NKF, LGLR, WDL, NMKF, FDSL and FDGK synergistically or additively enhanced the saltiness of a 0.30% NaCl solution. Molecular docking revealed that these peptides predominantly interacted with TMC4 by hydrogen bonding, with hydrophilic amino acids from both peptides and TMC4 playing a pivotal role in their binding. Furthermore, Leu217, Gln377, Glu378, Pro474 and Cys475 were postulated as the key binding sites of TMC4. These findings establish a robust theoretical foundation for salt reduction strategies in food and provide novel insights into the potential applications of yeast proteins.

Attenuation of neuronal ferroptosis in intracerebral hemorrhage by inhibiting HDAC1/2: Microglial heterogenization via the Nrf2/HO1 pathway.

AIM: The class I histone deacetylases (HDACs) implicate in microglial heterogenization and neuroinflammation following Intracerebral hemorrhage (ICH). Ferroptosis has also been reported in the ICH model. However, the relationship between HDAC1/2's role in microglial heterogenization and neuronal ferroptosis remains unclear. METHODS: In both in vivo and in vitro models of ICH, we used Romidepsin (FK228), a selective HDAC1/2 inhibitor, to investigate its effects on microglial heterogenization and neuronal ferroptosis. In the in vitro ICH model using Hemin, a transwell system was utilized to examine how microglia-driven inflammation and ICH-triggered neuronal ferroptosis interact. Immunostaining, Western blotting and RT-qPCR were used to evaluate the microglial heterogenization and neuronal ferroptosis. Microglial heterogenization, neuronal ferroptosis, and neurological dysfunctions were assessed in vivo ICH mice model performed by autologous blood injection. RESULTS: HDAC1/2 inhibition altered microglial heterogenization after ICH, as showing the reducing neuroinflammation and shifting microglia towards an anti-inflammatory phenotype by immunostaining and qPCR results. HDAC1/2 inhibition reduced ferroptosis, characterized by high ROS and low GPx4 expression in HT22 cells, and reduced iron and lipid deposition post-ICH in vivo. Additionally, the Nrf2/HO1 signaling pathway, especially acetyl-Nrf2, activated in the in vivo ICH model due to HDAC1/2 inhibition, plays a role in regulating microglial heterogenization. Furthermore, HDAC1/2 inhibition improved sensorimotor and histological outcomes post-ICH, offering a potential mechanism against ICH. CONCLUSION: Inhibition of HDAC1/2 reduces neuro-ferroptosis by modifying the heterogeneity of microglia via the Nrf2/HO1 pathway, with a particular focus on acetyl-Nrf2. Additionally, this inhibition aids in the faster removal of hematomas and lessens prolonged neurological impairments, indicating novel approach for treating ICH.

NADPH and NAC synergistically inhibits chronic ocular hypertension-induced neurodegeneration and neuroinflammation through regulating p38/MAPK pathway and peroxidation.

Glaucoma, the leading cause of irreversible blindness worldwide, is characterized by neurodegeneration and neuroinflammation with retinal NAD/NADP and GSH decline. Nicotinamide adenine dinucleotide (NAD)/NAD phosphate (NADP) and glutathione (GSH) are two redox reducers in neuronal and glial metabolism. However, therapeutic strategies targeting NAD/NADP or GSH do not exert ideal effects, and the underlying mechanisms are still poorly understood. We assessed morphological changes in retinal ganglion cells (RGCs), the affected neurons in glaucoma, and Müller cells, the major glial cells in the retina, as well as the levels of phosphorylated p38 (p-p38) and Caspase-3 in glaucoma patients. We constructed a modified chronic ocular hypertensive rat model and an oxygen-glucose deprivation (OGD) cell model. After applying NADPH and N-acetylcysteine (NAC), a precursor to cysteine, the rate-limiting substrate in GSH biosynthesis, to cells, apoptosis, axonal damage and peroxidation were reduced in the RGCs of the NAC group and p-p38 levels were decreased in the RGCs of the NADPH group, while in stimulated Müller cells cultured individually or cocultured with RGCs, gliosis and p38/MAPK, rather than JNK/MAPK, activation were inhibited. The results were more synergistic in the rat model, where either NADPH or NAC showed crossover effects on inhibiting peroxidation and p38/MAPK pathway activation. Moreover, the combination of NADPH and NAC ameliorated RGC electrophysiological function and prevented Müller cell gliosis to the greatest extent. These data illustrated conjoined mechanisms in glaucomatous RGC injury and Müller cell gliosis and suggested that NADPH and NAC collaborate as a neuroprotective and anti-inflammatory combination treatment for glaucoma and other underlying human neurodegenerative diseases.

Endovascular management of basilar artery aneurysms: a consecutive series of 124 patients.

BACKGROUND: There is currently no established criterion for determining when interventional treatment is necessary and what strategy is appropriate for basilar artery (BA) aneurysms. Through this study, we aimed to propose an algorithm that can effectively determine the optimal endovascular treatment (EVT) option for BA aneurysms. METHODS: We enrolled patients with BA aneurysms from June 2016 to December 2022 and performed procedures based on the algorithm. The analysis included demographic, clinical, and aneurysmal characteristics, procedural details, complications, angiographic outcomes, and clinical outcomes. RESULTS: This study included 124 patients (mean age 55.0 years) with a BA aneurysm who underwent EVT. Of these, 21 aneurysms were treated in the setting of subarachnoid hemorrhage (SAH). The majority of aneurysms were located at the basilar apex (74), followed by the basilar trunk (30) and vertebrobasilar junction (20). Coiling was used in 18.5% of cases, while stent-assisted coiling embolization was chosen for 58.9%. Overlapping stents were used in 12.9%, flow diverter (FD) implantation in 3.2%, Y/T stent techniques in 4.8%, and stent adjunctive coiling with unilateral vertebral artery (VA) occlusion in only 1.6%. Procedure-related complications occurred in 15 patients (12.1%). Patients had a modified Rankin Scale(mRS) score of 0.74±1.62; 98 (86.7%) had good prognosis with mRS scores ranging from 0 to 2 at the last follow-up. DSA was performed on 105 (84.7%) patients revealing that 101 (81.5%) achieved complete or near-complete occlusion. CONCLUSIONS: The endovascular treatment criteria for BA aneurysms depended on the multi-characteristics was safe and effective. However, further evidence is needed from large cohort studies.

Application of individual brain connectome in chronic ischemia: mapping symptoms before and after reperfusion.

How brain functions in the distorted ischemic state before and after reperfusion is unclear. It is also uncertain whether there are any indicators within ischemic brain that could predict surgical outcomes. To alleviate these issues, we applied individual brain connectome in chronic steno-occlusive vasculopathy (CSOV) to map both ischemic symptoms and their postbypass changes. A total of 499 bypasses in 455 CSOV patients were collected and followed up for 47.8 ± 20.5 months. Using multimodal parcellation with connectivity-based and pathological distortion-independent approach, areal MR features of brain connectome were generated with three measurements of functional connectivity (FC), structural connectivity, and PageRank centrality at the single-subject level. Thirty-three machine-learning models were then trained with clinical and areal MR features to obtain acceptable classifiers for both ischemic symptoms and their postbypass changes, among which, 11 were deemed acceptable (AUC > 0.7). Notably, the FC feature-based model for long-term neurological outcomes performed very well (AUC > 0.8). Finally, a Shapley additive explanations plot was adopted to extract important individual features in acceptable models to generate "fingerprints" of brain connectome. This study not only establishes brain connectomic fingerprint databases for brain ischemia with distortion, but also provides informative insights for how brain functions before and after reperfusion.

Qualifying Event and Recurrence of Ischemic Stroke in Symptomatic Artery Occlusion: A Post Hoc Analysis of CMOSS.

BACKGROUND: The authors aimed to elucidate the relationship between latest ischemic event and the incidence of subsequent ischemic stroke in patients with symptomatic artery occlusion. METHODS AND RESULTS: We analyzed the association between qualifying event-the latest ischemic event (transient ischemic attack [TIA] or stroke)-and the incidence of ipsilateral ischemic stroke in patients with symptomatic artery occlusion treated with medical therapy alone in CMOSS (Carotid or Middle Cerebral Artery Occlusion Surgery Study). The incidence of CMOSS primary outcomes, including any stroke or death within 30 days after randomization or ipsilateral ischemic stroke between 30 days and 2 years, between the bypass surgical and medical groups, stratified by qualifying events, was also compared. Of the 165 patients treated with medical therapy alone, 75 had a TIA and 90 had a stroke as their qualifying event. The incidence of ipsilateral ischemic stroke did not significantly differ between patients with a TIA and those with a stroke as their qualifying event (13.3% versus 6.7%, P=0.17). In multivariate analysis, the qualifying event was not associated with the incidence of ipsilateral ischemic stroke. There were no significant differences in the CMOSS primary outcomes between the surgical and medical groups, regardless of the qualifying event being TIA (10.1% versus 12.2%, P=0.86) or stroke (6.7% versus 8.9%, P=0.55). CONCLUSIONS: Among patients with symptomatic artery occlusion and hemodynamic insufficiency, the risk of subsequent ipsilateral ischemic stroke does not appear to be lower in patients presenting with a TIA compared with those with a stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01758614.

Potential of body mass index as a screening indicator for extracranial-intracranial bypass surgery in patients with symptomatic artery occlusion: a post-hoc analysis of the CMOSS trial.

BACKGROUND: To investigate the association between body mass index (BMI) and the incidence of ischemic stroke in patients with symptomatic artery occlusion, and further to evaluate the utility of BMI as a screening tool for identifying candidates for extracranial-intracranial bypass surgery. MATERIALS AND METHODS: We analyzed the relationship between BMI and the occurrence of ipsilateral ischemic stroke (IIS) among patients receiving only medical management in the Carotid or Middle cerebral artery Occlusion Surgery Study (CMOSS). Additionally, we compared the primary endpoint of CMOSS-stroke or death within 30 days, or IIS after 30 days up to two years-among patients with varying BMIs who underwent either surgery or medical treatment. RESULTS: Of the 165 patients who treated medically only, 16 (9.7%) suffered an IIS within two years. BMI was independently associated with the incidence of IIS (hazard ratio: 1.16 per kg/m2; 95% confidence interval: 1.06-1.27). The optimal BMI cutoff for predicting IIS was 24.5 kg/m2. Patients with BMI ≥24.5 kg/m2 experienced a higher incidence of IIS compared to those with BMI <24.5 kg/m2 (17.4% vs. 0.0%, P<0.01). The incidence of the CMOSS primary endpoint was significantly different between the surgical and medical groups for patients with BMI ≥24.5 kg/m2 (5.3% vs. 19.8%, P<0.01) and those with BMI <24.5 kg/m2 (10.6% vs. 1.4%; P=0.02). Surgical intervention was independently associated with a reduced rate of the CMOSS primary endpoint in patients with BMI ≥24.5 kg/m2. CONCLUSION: Data from the CMOSS trial indicate that patients with BMI ≥24.5 kg/m2 are at a higher risk of IIS when treated medically only and appear to derive greater benefit from bypass surgery compared to those with lower BMIs. Given the small sample size and the inherent limitations of retrospective analyses, further large-scale, prospective studies are necessary to confirm these findings.

Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter study: 1-year outcomes.

OBJECTIVE: Previous randomized controlled trials have reported a significantly higher occlusion rate of large and giant aneurysms when utilizing the Tubridge flow diverter (FD). In the present trial, the safety and efficacy of the Tubridge FD in treating unruptured internal carotid artery (ICA) or vertebral artery (VA) aneurysms were assessed in a real-world setting. METHODS: The Intracranial Aneurysms Managed by Parent Artery Reconstruction Using Tubridge Flow Diverter (IMPACT) study is a prospective, multicenter, single-arm clinical trial assessing the efficacy of the Tubridge FD in the management of unruptured aneurysms located in the ICA or VA. The primary endpoint was the complete occlusion (Raymond-Roy class 1) rate at the 1-year follow-up. The secondary endpoints included the technical success rate, the successful occlusion rate of the aneurysm, which is the degree of aneurysm embolization scored as Raymond-Roy class 1 or 2, major (> 50%) in-stent stenosis, and incidence of disabling stroke or neurological death associated with the target aneurysms. RESULTS: This study included 14 interventional neuroradiology centers, with 200 patients and 240 aneurysms. According to angiographic core laboratory assessment, 205 (85.4%) aneurysms were located in the ICA, 34 (14.2%) in the VA, and 1 (0.4%) in the middle cerebral artery. Additionally, 189 (78.8%) aneurysms were small (< 10 mm). At the 12-month follow-up, the total occlusion rate was 79.0% (166/210, 95% CI 72.91%-84.34%). Additionally, the occurrence of disabling stroke or neurological death related to the specified aneurysms was 1% (2/200). CONCLUSIONS: The 1-year results from the IMPACT trial affirm the safety record of use of the Tubridge FD in the treatment of intracranial aneurysms in real-world scenarios. These results reveal low morbidity and mortality rates of 3.5% and 1.5%, respectively. Furthermore, they provide evidence of the effectiveness of the Tubridge FD, as demonstrated by the complete occlusion achieved in 166 of 210 (79%) cases.

Clinical Outcomes On Tubridge Flow Diverter in Treatmenting Intracranial Aneurysms: a Retrospective Multicenter Registry Study.

PURPOSE: In China, the application of nitinol Tubridge flow diverter (TFD) has become popular for treating intracranial aneurysms (IAs). In this study, we investigated the safety outcomes of the application of TFD for treating IAs in real-world scenarios. METHODS: We retrospectively analyzed aneurysms treated with TFD in 235 centers throughout China between April 2018 and April 2020. The primary endpoint was the event-free survival rate at 12 months, defined as the occurrence of morbidity (spontaneous rupture, intraparenchymal hemorrhage (IPH), ischemic stroke, and permanent cranial neuropathy) or death. Univariate and multivariate analyses were performed to assess the risk factors. A good outcome was defined as a modified Rankin Score (mRS) of 0-2. RESULTS: We included 1281 unruptured aneurysms treated with TFD. The overall neurological morbidity and death rates after 12 months were 5.4 and 2.8%, respectively. Ischemic strokes were the most common complication (4.2%, P < 0.001). Cranial neuropathy, IPH, and spontaneous rupture occurred in 0.3%, 0.3%, and 0.5% of aneurysms, respectively. Univariate and multivariate analyses indicated that the male gender, older age, larger aneurysm diameter, and aneurysm located on BA were the independent risk factors for neurologic events. Aneurysm located on BA was the independent risk factor for ischemic strokes. Most patients (1222) had access to the mRS, and 93.2% of them achieved good outcomes. CONCLUSION: Treatment of IAs with TFD was associated with low morbidity and mortality, most of which were ischemic events. Large posterior aneurysms might be associated with a higher complication rate. TRIAL REGISTRATION: Retrospectively registered.