Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system.

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

Gender potentially affects early postoperative hyponatremia in pituitary adenoma: XGBoost-based predictive modeling.

Purpose: The occurrence of hyponatremia is a prevalent complication following transnasal transsphenoidal surgery for pituitary adenoma surgery, which adversely affects patient prognosis, hospitalization duration, and rehospitalization risk. The primary objective of this study is to strengthen the correlation between clinical factors associated with pituitary adenoma and postoperative hyponatremia. Additionally, the study aims to develop a predictive model for postoperative hyponatremia in patients with pituitary adenoma, with the ultimate goal of establishing a basis for reducing the occurrence of postoperative hyponatremia following surgical interventions. Methods: The chi-square test or Fisher test was employed for nominal data, while the t-test or Mann-Whitney test was utilized for continuous data analysis. In cases where the data exhibited statistical differences, binary logistic analysis was conducted to examine the risk and protective factors associated with postoperative hyponatremia. XGBoost was employed to construct predictive models for hyponatremia in this study. The patients were partitioned into training and test sets, and the most suitable parameters were determined through five-fold cross-validation and subsequently utilized for training on the training set. The discriminatory capability was assessed on the internal validation set. Results and conclusions: Out of the total 280 patients included in this investigation, 82 patients experienced early postoperative hyponatremia. Among these individuals, male gender (P = 0.02, odds ratio = 1.98) was identified as a risk factor for early postoperative hyponatremia, while preoperative chloride levels (P = 0.021, odds ratio = 0.866) and surgery time (P = 0.039, odds ratio = 0.990) were identified as protective factors against postoperative hyponatremia. The XGBoost model exhibited a sensitivity of 94.2%, a specificity of 61.5%, a positive predictive value of 51.6%, a negative predictive value of 96%, and identified male gender, preoperative sodium, and preoperative cortisol as the most significant predictors. Our findings indicate that gender may have influence in the development of early postoperative hyponatremia in patients with pituitary adenomas.

Hydrogen exerts neuroprotective effects after subarachnoid hemorrhage by attenuating neuronal ferroptosis and inhibiting neuroinflammation.

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH), the third most common stroke subtype, is associated with high mortality and disability rates. Therefore, finding effective therapies to improve neurological function after SAH is critical. The objective of this study was to investigate the potential neuroprotective effects of hydrogen in the context of SAH, specifically, by examining its role in attenuating neuronal ferroptosis and inhibiting neuroinflammation, which are exacerbated by excess iron ions after SAH. METHODS: Mice were exposed to chambers containing 3% hydrogen, and cells were cultured in incubators containing 60% hydrogen. Neurological function in mice was assessed using behavioral scores. Protein changes were detected using western blotting. Inflammatory factors were detected using enzyme linked immunosorbent assay. Probes, electron microscopy, and related kits were employed to detect oxidative stress and ferroptosis. RESULTS: Hydrogen improved the motor function, sensory function, and cognitive ability of mice after SAH. Additionally, hydrogen facilitated Nuclear factor erythroid 2 -related factor 2 activation, upregulated Glutathione peroxidase 4, and inhibited Toll-like receptor 4, resulting in downregulation of inflammatory responses, attenuation of oxidative stress after SAH, and inhibition of neuronal ferroptosis. CONCLUSION: Hydrogen exerts neuroprotective effects by inhibiting neuronal ferroptosis and attenuating neuroinflammation after SAH.

Novel perfluorocarbon-based oxygenation therapy alleviates Post-SAH hypoxic brain injury by inhibiting HIF-1α.

In comparison to other stroke types, subarachnoid hemorrhage (SAH) is characterized by an early age of onset and often results in poor prognosis. The inadequate blood flow at the site of the lesion leads to localized oxygen deprivation, increased level of hypoxia-inducible factor-1α (HIF-1α), and triggers inflammatory responses and oxidative stress, ultimately causing hypoxic brain damage. Despite the potential benefits of oxygen (O2) administration, there is currently a lack of efficient focal site O2 delivery following SAH. Conventional clinical O2 supply methods, such as transnasal oxygenation and hyperbaric oxygen therapy, do not show the ideal therapeutic effect in severe SAH patients. The perfluorocarbon oxygen carrier (PFOC) demonstrates efficacy in transporting O2 and responding to elevated levels of CO2 at the lesion site. Through cellular experiments, we determined that PFOC oxygenation serves as an effective therapeutic approach in inhibiting hypoxia. Furthermore, our animal experiments showed that PFOC oxygenation outperforms O2 breathing, leading to microglia phenotypic switching and the suppression of inflammatory response via the inhibition of HIF-1α. Therefore, as a new type of O2 therapy after SAH, PFOC oxygenation can effectively reduce hypoxic brain injury and improve neurological function.

Menaquinone-4 attenuates ferroptosis by upregulating DHODH through activation of SIRT1 after subarachnoid hemorrhage.

BACKGROUND: Menaquinone-4(MK-4), the isoform of vitamin K2 in the brain, exerts neuroprotective effects against a variety of central nervous system disorders. This study aimed to demonstrate the anti-ferroptosis effects of MK-4 in neurons after SAH. METHODS: A subarachnoid hemorrhage (SAH) model was prepared by endovascular perforation in mice. In vitro hemoglobin stimulation of primary cortical neurons mimicked SAH. MK-4, Brequinar (BQR, DHODH inhibitor), and Selisistat (SEL, SIRT1 inhibitor) were administered, respectively. Subsequently, WB, immunofluorescence was used to determine protein expression and localization, and transmission electron microscopy was used to observe neuronal mitochondrial structure while other indicators of ferroptosis were measured. RESULTS: MK-4 treatment significantly upregulated the protein levels of DHODH; decreased GSH, PTGS2, NOX1, ROS, and restored mitochondrial membrane potential. Meanwhile, MK-4 upregulated the expression of SIRT1 and promoted its entry into the nucleus. BQR or SEL partially abolished the protective effect of MK-4 on, neurologic function, and ferroptosis. CONCLUSIONS: Taken together, our results suggest that MK-4 attenuates ferroptosis after SAH by upregulating DHODH through the activation of SIRT1.

Systemic Immune-Inflammation Index Predicts the Prognosis of Traumatic Brain Injury.

OBJECTIVE: Systemic inflammation following traumatic brain injury (TBI) has been extensively studied over the past decades, as it contributes significantly to the pathophysiological injury mechanisms and subsequent poor outcomes. Systemic immune-inflammation (SII) index is a novel biomarker of systemic inflammatory response. However, its predictive value regarding TBI prognosis in clinical practice remains insufficiently investigated. METHODS: A total of 102 TBI patients admitted to Nanjing Drum Tower Hospital from July 2019 to February 2022 were enrolled. We employed various statistical analyses to evaluate the correlation between inflammatory indicators upon admission and patient prognosis, compared the predictive accuracy of these indicators, and generated receiver operating curve analysis to test their prognostic performance. RESULTS: The SII index, platelet count, absolute lymphocyte count, and neutrophil/lymphocyte ratio (NLR) were capable of distinguishing TBI prognosis according to univariate logistic regression models (P < 0.05). Multivariate logistic regression models revealed that increased SII index, platelet count, and NLR upon admission were independent predictors of poor TBI prognosis (P < 0.05). Receiver operating curve analysis further demonstrated that the SII index (area under the curve = 0.845, 95% confidence interval 0.769-0.921, P = 0.000) exhibited higher predictive ability than the NLR (area under the curve = 0.694, 95% confidence interval 0.591-0.796, P = 0.001). CONCLUSIONS: Our findings suggested that increased SII index during the early stages of TBI was an independent risk factor for poor prognosis with satisfactory predictive value. The SII index provides a reliable, convenient, and cost-effective prognostic model to evaluate systemic inflammation after TBI and identify patients at risk of poor outcomes, thereby offering valuable guidance for clinical practice.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

Dihydromyricetin confers cerebroprotection against subarachnoid hemorrhage via the Nrf2-dependent Prx2 signaling cascade.

BACKGROUND: Several clinical and experimental studies have shown that therapeutic strategies targeting oxidative damage are beneficial for subarachnoid hemorrhage (SAH). A brain-permeable flavonoid, dihydromyricetin (DHM), can modulate redox/oxidative stress and has cerebroprotective effects in several neurological disorders. The effects of DHM on post-SAH early brain injury (EBI) and the underlying mechanism have yet to be clarified. PURPOSE: This work investigated a potential role for DHM in SAH, together with the underlying mechanisms. METHODS: Cerebroprotection by DHM was studied using a SAH rat model and primary cortical neurons. Atorvastatin (Ato) was a positive control drug in this investigation. The effects of DHM on behavior after SAH were evaluated by performing the neurological rotarod and Morris water maze tests, as well as by examining its effects on brain morphology and on the molecular and functional phenotypes of primary cortical neurons using dichlorodihydrofluorescein diacetate (DCFH-DA), immunofluorescent staining, biochemical analysis, and Western blot. RESULTS: DHM was found to significantly reduce the amount of reactive oxygen species (ROS), suppress mitochondrial disruption, and increase intrinsic antioxidant enzymatic activity following SAH. DHM also significantly reduced neuronal apoptosis in SAH rats and improved short- and long-term neurological functions. DHM induced significant increases in peroxiredoxin 2 (Prx2) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression, while decreasing phosphorylation of p38 and apoptotic signal-regulated kinase 1 (ASK1). In contrast, reduction of Prx2 expression using small interfering ribonucleic acid or by inhibiting Nrf2 with ML385 attenuated the neuroprotective effect of DHM against SAH. Moreover, DHM dose-dependently inhibited oxidative damage, decreased neuronal apoptosis, and increased the viability of primary cultured neurons in vitro. These positive effects were associated with Nrf2 activation and stimulation of Prx2 signaling, whereas ML385 attenuated the beneficial effects. CONCLUSION: These results reveal that DHM protects against SAH primarily by modulating the Prx2 signaling cascade through the Nrf2-dependent pathway. Hence, DHM could be a valuable therapeutic candidate for SAH treatment.

P38-DAPK1 axis regulated LC3-associated phagocytosis (LAP) of microglia in an in vitro subarachnoid hemorrhage model.

BACKGROUND: The phagocytosis and homeostasis of microglia play an important role in promoting blood clearance and improving prognosis after subarachnoid hemorrhage (SAH). LC3-assocaited phagocytosis (LAP) contributes to the microglial phagocytosis and homeostasis via autophagy-related components. With RNA-seq sequencing, we found potential signal pathways and genes which were important for the LAP of microglia. METHODS: We used an in vitro model of oxyhemoglobin exposure as SAH model in the study. RNA-seq sequencing was performed to seek critical signal pathways and genes in regulating LAP. Bioparticles were used to access the phagocytic ability of microglia. Western blot (WB), immunoprecipitation, quantitative polymerase chain reaction (qPCR) and immunofluorescence were performed to detect the expression change of LAP-related components and investigate the potential mechanisms. RESULTS: In vitro SAH model, there were increased inflammation and decreased phagocytosis in microglia. At the same time, we found that the LAP of microglia was inhibited in all stages. RNA-seq sequencing revealed the importance of P38 MAPK signal pathway and DAPK1 in regulating microglial LAP. P38 was found to regulate the expression of DAPK1, and P38-DAPK1 axis was identified to regulate the LAP and homeostasis of microglia after SAH. Finally, we found that P38-DAPK1 axis regulated expression of BECN1, which indicated the potential mechanism of P38-DAPK1 axis regulating microglial LAP. CONCLUSION: P38-DAPK1 axis regulated the LAP of microglia via BECN1, affecting the phagocytosis and homeostasis of microglia in vitro SAH model. Video Abstract.

Intraoperative Hemodynamics of Parasylvian Cortical Arteries for Predicting Postoperative Symptomatic Cerebral Hyperperfusion after Direct Revascularization in Patients with Moyamoya Disease: A Preliminary Study.

Objective. The search for methods by which to predict the risks of cerebral hyperperfusion syn-drome (CHS) in adults with moyamoya disease (MMD), including those utilizing new biomarkers, still deserves further research. The objective of this study was to investigate the association between the hemodynamics of parasylvian cortical arteries (PSCAs) and postoperative CHS. Methods. A consecutive number of adults with MMD who had undergone direct bypass between September 2020 and December 2022 were recruited. Intraoperative microvascular doppler ultrasonography (MDU) was performed to evaluate the hemodynamics of PSCAs. The intraoperative flow direction, mean value of velocity (MVV) of recipient artery (RA) and bypass graft were recorded. According to flow direction after bypass, RA was divided into entering sylvian (RA.ES) and leaving sylvian (RA.LS) subtypes. Univariate, multivariate, and ROC analyses of the risk factors for postoperative CHS were performed. Results. A total of 16 (15.09%) cases in 106 consecutive hemispheres (101 patients) sat-isfied the postoperative CHS criteria. According to univariate analysis, advanced Suzuki stage, MVV of RA before bypass, and fold increase of MVV in RA.ES after bypass were significantly associated with postoperative CHS (p < 0.05). Multivariate analysis indicated that left-operated hemisphere (OR (95%CI), 4.58 (1.05-19.97), p = 0.043), advanced Suzuki stage (OR (95%CI), 5.47 (1.99-15.05), p = 0.017), and fold increase of MVV in RA.ES (OR (95%CI), 1.17 (1.06-1.30), p = 0.003) were statistically significantly associated with the occurrence of CHS. The cut-off value of fold increase of MVV in RA.ES was 2.7-fold (p < 0.05). Conclusions. Left-operated hemisphere, advanced Suzuki stage, and postoperative fold increase of MVV in RA.ES were potential risk factors for postoperative CHS. Intraoperative MDU was useful for evaluating hemodynamics and predicting CHS.

Pre-operative prognostic nutrition index and post-operative pneumonia in aneurysmal subarachnoid hemorrhage patients.

Background and objective: Post-operative pneumonia (POP), a common complication, may be associated with prolonged hospitalization and long-term mortality in aneurysmal subarachnoid hemorrhage (aSAH) patients. This study aimed to explore the association between pre-operative prognostic nutrition index (PNI) and POP in aSAH patients. Methods: A total of 280 aSAH patients were enrolled from Nanjing Drum Tower Hospital. PNI was calculated as follows: [10 × albumin(gr/dl)] + [0.005 × absolute pre-operative lymphocyte count (per mm3)]. We utilized multivariate analyses, restricted cubic spline, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to elucidate the role of PNI in POP. Results: Pre-operative PNI levels in the POP group were higher, compared with the non-POP group (41.0 [39.0, 45.4] vs. 44.4 [40.5, 47.3], P = 0.001). When we included PNI as a categorical variable in the multivariate analysis, the levels of PNI were associated with POP (odds ratio, 0.433; 95% confidence interval, 0.253-0.743; P=0.002). In addition, when we included PNI as a continuous variable in the multivariate analysis, the PNI levels were also associated with POP (odds ratio, 0.942; 95% confidence interval, 0.892-0.994; P = 0.028). The level of albumin was also a predictor of the occurrence of POP, with a lower diagnostic power than PNI [AUC: 0.611 (95% confidence interval, 0.549-0.682; P = 0.001) for PNI vs. 0.584 (95% confidence interval, 0.517-0.650; P = 0.017) for albumin]. Multivariable-adjusted spline regression indicated a linear dose-response association between PNI and POP in aSAH participants (P for linearity = 0.027; P for non-linearity = 0.130). Reclassification assessed by IDI and NRI was significantly improved with the addition of PNI to the conventional model of POP in aSAH patients (NRI: 0.322 [0.089-0.555], P = 0.007; IDI: 0.016 [0.001-0.031], P = 0.040). Conclusion: The lower levels of pre-operative PNI may be associated with the higher incidence of POP in aSAH patients. Neurosurgeons are supposed to pay more attention to pre-operative nutrition status in aSAH patients.

A Case of Craniocervical Junction Arteriovenous Fistulas with a Brainstem Mass Lesion on Imaging: Case Report and Literature Review.

Intracranial mass lesions occur within the cranial cavity, and their etiology is diverse. Although tumors and hemorrhagic diseases are the common causes, some rarer etiologies, such as vascular malformations, might also present with intracranial mass lesion manifestations. Such lesions are easily misdiagnosed due to the lack of manifestations of the primary disease. The treatment involves a detailed examination and differential diagnosis of the etiology and clinical manifestations. On 26 October 2022, a patient with craniocervical junction arteriovenous fistulas (CCJAVFs) was admitted to Nanjing Drum Tower Hospital. Imaging examinations showed a brainstem mass lesion, and the patient was initially diagnosed with a brainstem tumor. After a thorough preoperative discussion and a digital subtraction angiography (DSA) examination, the patient was diagnosed with CCJAVF. The patient was cured using interventional treatment, and an invasive craniotomy was not required. During diagnosis and treatment, the cause of the disease might not be apparent. Thus, a comprehensive preoperative examination is very important, and physicians need to conduct the diagnosis and differential diagnosis of the etiology based on the examination to administer precise treatment and reduce unnecessary operations.

Hydrogen inhalation therapy regulates lactic acid metabolism following subarachnoid hemorrhage through the HIF-1α pathway.

The neuroprotective effects of hydrogen have been demonstrated, but the mechanism is still poorly understood. In a clinical trial of inhaled hydrogen in patients with subarachnoid hemorrhage (SAH), we found that hydrogen reduced the accumulation of lactic acid in the nervous system. There are no studies demonstrating the regulatory effect of hydrogen on lactate and in this study we hope to further clarify the mechanism by which hydrogen regulates lactate metabolism. In cell experiments, PCR and Western Blot showed that HIF-1α was the target related to lactic acid metabolism that changed the most before and after hydrogen intervention. HIF-1α levels were suppressed by hydrogen intervention treatment. Activation of HIF-1α inhibited the lactic acid-lowering effect of hydrogen. We have also demonstrated the lactic acid-lowering effect of hydrogen in animal studies. Our work clarifies that hydrogen can regulate lactate metabolism via the HIF-1αpathway, providing new insights into the neuroprotective mechanisms of hydrogen.

Risk factors of postoperative cerebral hyperperfusion syndrome and its relationship with clinical prognosis in adult patients with moyamoya disease.

BACKGROUND: To investigate the incidence, risk factors, and clinical prognosis of cerebral hyperperfusion syndrome (CHS) after superficial temporal artery-middle cerebral artery anastomosis combined with encephalo-duro-arterio-synangiosis (STA-MCA/EDAS) in adult patients with moyamoya disease (MMD). METHODS: The clinical data of 160 adult patients with MMD treated by STA-MCA/EDAS from January 2016 to January 2017 were retrospectively analyzed. According to CHS diagnosis, MMD patients were divided into CHS and non-CHS group. Univariate and multivariate analysis of risk factors and Kaplan-Meier curve of stroke-free survival for CHS were performed. RESULTS: A total of 12 patients (7.5%) developed postoperative CHS, of which 4 patients (2.5%) presented with cerebral hemorrhage. Univariate and multivariate analysis showed moyamoya vessel on the surgical hemisphere (OR = 3.04, 95% CI = 1.02-9.03, P = 0.046) and left operated hemisphere (OR = 5.16, 95% CI = 1.09-21.34, P = 0.041) were independent risk factors for CHS. The other variables, such as age, gender, presentation, hypertension, diabetes, smoking, mean mRS score on admission, modified Suzuki stage and pre-infarction stage on surgical hemisphere, and bypass patency, had no association with postoperative CHS (P > 0.05). At final follow-up with average 38 months, there were 18 out of 133 patients (13.5%, 4.91% per person year) presented with newly developed complications. There was no significant difference between newly developed complications, mean mRS scores, and Kaplan-Meier curve of stroke-free survival in patients with and without CHS (P > 0.05). CONCLUSION: The concentration of moyamoya vessels and left operated hemisphere was independent risk factors for CHS, which could not affect the clinical prognosis if treated timely and properly. The current study offers a new perspective of moyamoya vessels and supporting data for choosing MMD candidates on cerebral revascularization.

Diagnosis potential of subarachnoid hemorrhage using miRNA signatures isolated from plasma-derived extracellular vesicles.

The diagnosis and clinical management of aneurysmal subarachnoid hemorrhage (aSAH) is currently limited by the lack of accessible molecular biomarkers that reflect the pathophysiology of disease. We used microRNAs (miRNAs) as diagnostics to characterize plasma extracellular vesicles in aSAH. It is unclear whether they can diagnose and manage aSAH. Next-generation sequencing (NGS) was used to detect the miRNA profile of plasma extracellular vesicles (exosomes) in three patients with SAH and three healthy controls (HCs). We identified four differentially expressed miRNAs and validated the results using quantitative real-time polymerase chain reaction (RT-qPCR) with 113 aSAH patients, 40 HCs, 20 SAH model mice, and 20 sham mice. Exosomal miRNA NGS revealed that six circulating exosomal miRNAs were differentially expressed in patients with aSAH versus HCs and that the levels of four miRNAs (miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p) were differentially significant. After multivariate logistic regression analysis, only miR-369-3p, miR-486-3p, and miR-193b-3p enabled prediction of neurological outcomes. In a mouse model of SAH, greater expression of miR-193b-3p and miR-486-3p remained statistically significant relative to controls, whereas expression levels of miR-369-3p and miR-410-3p were lower. miRNA gene target prediction showed six genes associated with all four of these differentially expressed miRNAs. The circulating exosomes miR-369-3p, miR-410-3p, miR-193b-3p, and miR-486-3p may influence intercellular communication and have potential clinical utility as prognostic biomarkers for aSAH patients.

Lipid-accumulated reactive astrocytes promote disease progression in epilepsy.

Reactive astrocytes play an important role in neurological diseases, but their molecular and functional phenotypes in epilepsy are unclear. Here, we show that in patients with temporal lobe epilepsy (TLE) and mouse models of epilepsy, excessive lipid accumulation in astrocytes leads to the formation of lipid-accumulated reactive astrocytes (LARAs), a new reactive astrocyte subtype characterized by elevated APOE expression. Genetic knockout of APOE inhibited LARA formation and seizure activities in epileptic mice. Single-nucleus RNA sequencing in TLE patients confirmed the existence of a LARA subpopulation with a distinct molecular signature. Functional studies in epilepsy mouse models and human brain slices showed that LARAs promote neuronal hyperactivity and disease progression. Targeting LARAs by intervention with lipid transport and metabolism could thus provide new therapeutic options for drug-resistant TLE.