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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.
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Encéfalo , Electroencefalografía , Encéfalo/fisiología , Mapeo Encefálico , Perfusión , Circulación CerebrovascularRESUMEN
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.
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Accidente Cerebrovascular , Hemorragia Subaracnoidea , Humanos , Animales , Ratones , Hemorragia Subaracnoidea/tratamiento farmacológico , Taurina/farmacología , Astrocitos , Apoptosis , AminoácidosRESUMEN
BACKGROUND: Moyamoya disease (MMD) is a serious intracranial cerebrovascular disease. Cerebral hemorrhage caused by MMD will bring life risk to patients. Therefore, MMD detection is of great significance in the prevention of cerebral hemorrhage. In order to improve the accuracy of digital subtraction angiography (DSA) in the diagnosis of ischemic MMD, in this paper, a deep network architecture combined with 3D convolutional neural network (3D CNN) and bidirectional convolutional gated recurrent unit (BiConvGRU) is proposed to learn the spatiotemporal features for ischemic MMD detection. METHODS: Firstly, 2D convolutional neural network (2D CNN) is utilized to extract spatial features for each frame of DSA. Secondly, the long-term spatiotemporal features of DSA sequence are extracted by BiConvGRU. Thirdly, the short-term spatiotemporal features of DSA are further extracted by 3D convolutional neural network (3D CNN). In addition, different features are extracted when gray images and optical flow images pass through the network, and multiple features are extracted by features fusion. Finally, the fused features are utilized to classify. RESULTS: The proposed method was quantitatively evaluated on a data sets of 630 cases. The experimental results showed a detection accuracy of 0.9788, sensitivity and specificity were 0.9780 and 0.9796, respectively, and area under curve (AUC) was 0.9856. Compared with other methods, we can get the highest accuracy and AUC. CONCLUSIONS: The experimental results show that the proposed method is stable and reliable for ischemic MMD detection, which provides an option for doctors to accurately diagnose ischemic MMD.
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Enfermedad de Moyamoya , Humanos , Enfermedad de Moyamoya/diagnóstico por imagen , Angiografía de Substracción Digital/métodos , Redes Neurales de la Computación , Hemorragia CerebralRESUMEN
BACKGROUND: The aim of this study was to explore the neuroanatomical bases of vascular mild cognitive impairment (VaMCI) with respect to attention/executive function, memory, language, and visuospatial function. METHODS: We used voxel-based morphometric analysis to identify brain regions that significantly differed in terms of gray matter volumes (GMVs) between 43 patients with VaMCI and 55 healthy controls. Then, we compared the individual GMVs of the selected regions with the neuropsychological profiles of the VaMCI patients. RESULTS: The delayed recall component of the Rey-Osterrieth Complex Figure Test (CFT) (74.4%), the Symbol Digit Modalities Test (74.4%), the Boston Naming Test (51.2%), and the CFT-copy (81.4%) shared the highest incidence of impairment in the 4 cognitive domains, respectively. Compared with controls, patients with VaMCI exhibited significantly reduced GMVs. This effect was mainly present in the frontal regions, including the bilateral dorsolateral prefrontal cortex (DLPFC), the orbital portion of the superior frontal gyrus (SFG), and the left supplemental motor area, and was also observed in the bilateral posterior cingulated cortex (PCC). GMVs were significantly correlated with performance in the Trail Making Test, part B, in the bilateral DLPFC and PCC, the clock drawing test in the right orbital portion of the SFG, and CFT-delayed recall in the right PCC. CONCLUSIONS: These results, from the perspective of brain morphology, uniquely explored the specific cerebral structural changes of VaMCI, thus providing a deeper understanding of the pathophysiology of the disease.
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Corteza Cerebral/patología , Disfunción Cognitiva/patología , Sustancia Gris/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/psicología , Atención/fisiología , Corteza Cerebral/irrigación sanguínea , Disfunción Cognitiva/complicaciones , Disfunción Cognitiva/fisiopatología , Complicaciones de la Diabetes , Función Ejecutiva/fisiología , Sustancia Gris/irrigación sanguínea , Humanos , Hipercolesterolemia/complicaciones , Hipertensión/complicaciones , Lenguaje , Imagen por Resonancia Magnética , Trastornos de la Memoria/patología , Recuerdo Mental/fisiología , Persona de Mediana Edad , Neuroimagen , Pruebas Neuropsicológicas , Tamaño de los Órganos , Conducta Espacial/fisiología , Adulto JovenRESUMEN
The receptor for advanced glycation end products (RAGE) gene expresses two major alternative splicing isoforms, full-length membrane-bound RAGE (mRAGE) and secretory RAGE (esRAGE). Both isoforms play important roles in Alzheimer's disease (AD) pathogenesis, either via interaction of mRAGE with ß-amyloid peptide (Aß) or inhibition of the mRAGE-activated signaling pathway. In the present study, we showed that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) and Transformer2ß-1 (Tra2ß-1) were involved in the alternative splicing of mRAGE and esRAGE. Functionally, two factors had an antagonistic effect on the regulation. Glucose deprivation induced an increased ratio of mRAGE/esRAGE via up-regulation of hnRNP A1 and down-regulation of Tra2ß-1. Moreover, the ratios of mRAGE/esRAGE and hnRNP A1/Tra2ß-1 were increased in peripheral blood mononuclear cells from AD patients. The results provide a molecular basis for altered splicing of mRAGE and esRAGE in AD pathogenesis. The receptor for advanced glycation end products (RAGE) gene expresses two major alternative splicing isoforms, membrane-bound RAGE (mRAGE) and secretory RAGE (esRAGE). Both isoforms play important roles in Alzheimer's disease (AD) pathogenesis. Mechanism for imbalanced expression of these two isoforms in AD brain remains elusive. We proposed here a hypothetic model to illustrate that impaired glucose metabolism in AD brain may increase the expression of splicing protein hnRNP A1 and reduce Tra2ß-1, which cause the imbalanced expression of mRAGE and esRAGE.
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Enfermedad de Alzheimer/patología , Encéfalo/metabolismo , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Proteínas de Unión al ARN/metabolismo , Receptores Inmunológicos/genética , Empalmosomas/metabolismo , Anciano , Línea Celular Tumoral , Células Cultivadas , Femenino , Regulación de la Expresión Génica/genética , Glucosa/deficiencia , Ribonucleoproteína Nuclear Heterogénea A1 , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Ribonucleoproteínas Nucleares Heterogéneas , Humanos , Leucocitos Mononucleares , Masculino , Modelos Biológicos , Proteínas del Tejido Nervioso/genética , Neuroblastoma/patología , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/metabolismo , Factores de Empalme Serina-Arginina , Empalmosomas/genética , TransfecciónRESUMEN
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.
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Ferroptosis , Microglía , Ratones , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedades Neuroinflamatorias , Hemorragia Cerebral/metabolismoRESUMEN
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.
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Cavernous sinus dural arteriovenous fistula (DAVF) was a special type of intracranial vascular malformation, and endovascular treatment was usually the first choice. However, sometimes it might fail for patients without the proper approach. Video 1 illustrates the case of a patient who presented with left exophthalmos and conjunctival hyperemia caused by cavernous sinus DAVF. Transarterial and transvenous embolization have been attempted but unsuccessful due to no pathways to the fistula. The orbital symptoms aggravated gradually. Therefore we performed combined microsurgical and endovascular treatment in a hybrid neurovascular operating room through direct puncture of caverous sinus by craniotomy and subsequent embolization. A zygomatic-pterional approach was used with epidural exposure of anterior clinoid process and cavernous sinus. After precise localization of the cavernous sinus, we directly punctured it until the blood spurted. An Echelon-10 microcatheter was inserted into cavernous sinus assisted by a Synchro microwire without any resistance. Microcathether angiography confirmed that it was in the true cavity of the cavernous sinus. Curative embolization was achieved successfully using coils and Onyx-18, and no procedure-related complications occurred. The orbital signs and symptoms significantly relieved after surgery and did not relapse at 6-month follow-up. Endovascular treatment remained the optimal choice for cavernous sinus DAVF. However, for practical cases without accessible pathways, combined microsurgical and endovascular management in a hybrid neurovascular operating room was feasible, although challenging. The patient gave informed consent for the procedure and video production.
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Seno Cavernoso , Malformaciones Vasculares del Sistema Nervioso Central , Embolización Terapéutica , Procedimientos Endovasculares , Humanos , Seno Cavernoso/diagnóstico por imagen , Seno Cavernoso/cirugía , Quirófanos , Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Malformaciones Vasculares del Sistema Nervioso Central/cirugía , Embolización Terapéutica/métodos , Angiografía Cerebral , Procedimientos Endovasculares/métodosRESUMEN
Vascular cognitive impairment (VCI) is a critical issue in moyamoya disease (MMD). However, the glucose metabolic pattern in these patients is still unknown. This study aimed to identify the metabolic signature of cognitive impairment in patients with MMD using 18F-2-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) and establish a classifier to identify VCI in patients with MMD. One hundred fifty-two patients with MMD who underwent brain 18F-FDG PET scans before surgery were enrolled and classified into nonvascular cognitive impairment (non-VCI, n = 52) and vascular cognitive impairment (VCI, n = 100) groups according to neuropsychological test results. Additionally, thirty-three health controls (HCs) were also enrolled. Compared to HCs, patients in the VCI group exhibited extensive hypometabolism in the bilateral frontal and cingulate regions and hypermetabolism in the bilateral cerebellum, while patients in the non-VCI group showed hypermetabolism only in the cerebellum and slight hypometabolism in the frontal and temporal regions. In addition, we found that the patients in the VCI group showed hypometabolism mainly in the left basal ganglia compared to those in the non-VCI group. The sparse representation-based classifier algorithm taking the SUVr of 116 Anatomical Automatic Labeling (AAL) areas as features distinguished patients in the VCI and non-VCI groups with an accuracy of 82.4%. This study demonstrated a characteristic metabolic pattern that can distinguish patients with MMD without VCI from those with VCI, namely, hypometabolic lesions in the left hemisphere played a more important role in cognitive decline in patients with MMD.
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Disfunción Cognitiva , Enfermedad de Moyamoya , Humanos , Adulto , Fluorodesoxiglucosa F18/metabolismo , Enfermedad de Moyamoya/diagnóstico por imagen , Glucosa/metabolismo , Imagen por Resonancia Magnética , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Tomografía de Emisión de Positrones/métodos , AlgoritmosRESUMEN
OBJECTIVE: The safety and efficacy of embolization with Gamma Knife radiosurgery (GKRS) for high-grade brain arteriovenous malformations (bAVMs) are uncertain. The purpose of this study was to elucidate the long-term outcome of a tailored embolization strategy with GKRS and identify the independent factors associated with bAVM obliteration. METHODS: Between January 2014 and January 2017, a consecutive cohort of 159 patients with high-grade bAVMs who underwent embolization with GKRS was enrolled in this prospective single-center cohort study. All patients received a tailored embolization strategy with GKRS. The primary outcome was defined as bAVM obliteration. Secondary outcomes were neurological function and complications. RESULTS: After a mean follow-up of 40.4 months, 5 patients were lost to follow-up. One hundred eighteen of the remaining 154 patients had favorable neurological outcomes with complete bAVM obliteration. A decrease in bAVM nidus size was observed in 36 patients. Five patients developed intracranial hemorrhage during the latency period, and 2 patients died. The Kaplan-Meier analysis showed that the obliteration rate increased each year and reached the peak point at approximately 3 years. The multivariate Cox regression analysis of factors affecting bAVM obliteration revealed that postembolization bAVM volume < 10 cm3 (p = 0.02), supratentorial location (p < 0.01), staged embolization prior to GKRS (p < 0.01), and mean Spetzler-Martin (SM) grade (p < 0.01) were independent factors associated with a high obliteration rate. CONCLUSIONS: These data suggested that high-grade bAVMs treated using a tailored embolization strategy with GKRS were associated with a favorable clinical outcome and obliteration rate. Postembolization bAVM volume < 10 cm3, supratentorial location, staged embolization prior to GKRS, and low mean SM grade were associated with a high obliteration rate.
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Malformaciones Arteriovenosas Intracraneales , Radiocirugia , Humanos , Radiocirugia/efectos adversos , Resultado del Tratamiento , Estudios de Cohortes , Estudios Prospectivos , Estudios Retrospectivos , Malformaciones Arteriovenosas Intracraneales/complicaciones , Encéfalo , Estudios de SeguimientoRESUMEN
Background and purpose: Revascularization surgery for patients with moyamoya disease (MMD) is very complicated and has a high rate of postoperative complications. This pilot study aimed to prove the safety and efficacy of remote ischemic conditioning (RIC) in adult MMD patients undergoing revascularization surgery. Methods: A total of 44 patients with MMD were enrolled in this single-center, open-label, prospective, parallel randomized study, including 22 patients assigned to the sham group and 22 patients assigned to the RIC group. The primary outcome was the incidence of major neurologic complications during the perioperative period. Secondary outcomes were the modified Rankin Scale (mRS) score at discharge, at 90 days post-operation, and at 1 year after the operation. The outcome of safety was the incidence of adverse events associated with RIC. Blood samples were obtained to monitor the serum concentrations of cytokines (VEGF, IL-6). Results: No subjects experienced adverse events during RIC intervention, and all patients could tolerate the RIC intervention in the perioperative period. The incidence of major neurologic complications was significantly lower in the RIC group compared with the control group (18.2% vs. 54.5%, P = 0.027). The mRS score at discharge in the RIC group was also lower than the control group (0.86 ± 0.99 vs. 1.18 ± 1.22, P = 0.035). In addition, the serum IL-6 level increased significantly at 7 days after bypass surgery in the control group and the serum level of VEGF at 7 days post-operation in the RIC group. Conclusion: In conclusion, our study demonstrated the neuroprotective effect of RIC by reducing perioperative complications and improving cerebral blood flow in adult MMD patients undergoing revascularization surgery. Thus, RIC seems to be a potential treatment method for MMD. Clinical trial registration: ClinicalTrials.gov, identifier: NCT05860946.
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BACKGROUND: Although bypass surgery is an effective treatment for moyamoya vasculopathy (MMV), the incidence of postoperative complications is still high. This study aims to introduce a novel evaluating system based on individualised pathophysiology of MMV, and to assess its clinical significance. METHODS: This multicentre, prospective study enrolled adult patients with MMV from Huashan Hospital, Fudan University and National Center for Neurological Disorders, China between March 2021 and February 2022. Multimodal neuroimages containing structural and functional information were used to evaluate personalised disease severity and fused to localise the surgical field, avoid invalid regions and propose alternative recipient arteries. The recipient artery was further selected intraoperatively by assessing regional haemodynamic and electrophysiological information. The preanastomosis and postanastomosis data were compared with assist with the postoperative management. Patients who received such tailored revascularisations were included in the novel group and the others were included in the traditional group. The 30-day surgical outcomes and intermediate long-term follow-up were compared. RESULTS: Totally 375 patients (145 patients in the novel group and 230 patients in the traditional group) were included. The overall complication rate was significantly lower in the novel group (pË0.001). In detail, both the rates of postoperative infarction (p=0.009) and hyperperfusion syndrome (p=0.010) were significantly lower. The functional outcomes trended to be more favourable in the novel group, though not significantly (p=0.260). Notably, the proportion of good functional status was higher in the novel group (p=0.009). Interestingly, the preoperative statuses of perfusion and metabolism around the bypass area were significantly correlated with the occurrence of postoperative complications (PË0.0001). CONCLUSIONS: This novel evaluating system helps to identify appropriate surgical field and recipient arteries during bypass surgery for MMV to achieve better haemodynamic remodelling and pathophysiological improvement, which results in more favourable clinical outcomes.
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Unruptured intracranial aneurysm (UIA) is a high-risk cerebrovascular saccular dilatation, the effective medical management of which depends on high-performance diagnosis. However, most UIAs are diagnosed incidentally during neurovascular imaging modalities, which are time-consuming and harmful (e.g., radiation). Serum metabolic fingerprints is a promising alternative for early diagnosis of UIA. Here, nanoparticle enhanced laser desorption/ionization mass spectrometry is applied to obtain high-performance UIA-specific serum metabolic fingerprints. Diagnostic performance with an area-under-the-curve (AUC) of 0.842 (95% confidence interval (CI): 0.783-0.891) is achieved by the constructed machine learning (ML) model, including ML algorithm selection and feature selection. Lactate, glutamine, homoarginine, and 3-methylglutaconic acid are identified as the metabolic biomarker panel, which showed satisfactory diagnosis (AUC of 0.812, 95% CI: 0.727-0.897) and effective growth risk assessment (p<0.05, two-tailed t-test) of UIAs. This work aims to promote the diagnostics of UIAs and metabolic biomarker screening for medical management.
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Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico , Medición de Riesgo , Algoritmos , Área Bajo la Curva , BiomarcadoresRESUMEN
BACKGROUND: A variety of emerging medical imaging technologies based on artificial intelligence have been widely applied in many diseases, but they are still limitedly used in the cerebrovascular field even though the diseases can lead to catastrophic consequences. OBJECTIVE: This work aims to discuss the current challenges and future directions of artificial intelligence technology in cerebrovascular diseases through reviewing the existing literature related to applications in terms of computer-aided detection, prediction and treatment of cerebrovascular diseases. METHODS: Based on artificial intelligence applications in four representative cerebrovascular diseases including intracranial aneurysm, arteriovenous malformation, arteriosclerosis and moyamoya disease, this paper systematically reviews studies published between 2006 and 2021 in five databases: National Center for Biotechnology Information, Elsevier Science Direct, IEEE Xplore Digital Library, Web of Science and Springer Link. And three refinement steps were further conducted after identifying relevant literature from these databases. RESULTS: For the popular research topic, most of the included publications involved computer-aided detection and prediction of aneurysms, while studies about arteriovenous malformation, arteriosclerosis and moyamoya disease showed an upward trend in recent years. Both conventional machine learning and deep learning algorithms were utilized in these publications, but machine learning techniques accounted for a larger proportion. CONCLUSION: Algorithms related to artificial intelligence, especially deep learning, are promising tools for medical imaging analysis and will enhance the performance of computer-aided detection, prediction and treatment of cerebrovascular diseases.
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Malformaciones Arteriovenosas , Enfermedad de Moyamoya , Inteligencia Artificial , Humanos , Aprendizaje Automático , Enfermedad de Moyamoya/diagnóstico por imagenRESUMEN
BACKGROUND: Despite limited efficiency, modulation of microglia/macrophages has shown to attenuate neuroinflammation after intracerebral hemorrhage (ICH). In this context, we evaluated the efficacy of modified exosomal signal regulatory protein α (SIRPα) variants (SIRPα-v Exos) in microglia/macrophages and neuroinflammation-associated white matter injury after ICH. METHODS: SIRPα-v Exos were engineered to block CD47-SIRPα interactions. After obtaining SIRPα-v Exos from lentivirus-infected mesenchymal stem cells, C57BL/6 mice suffering from ICH underwent consecutive intravenous injections of SIRPα-v Exos (6 mg/kg) for 14 days. Afterwards, the volume of hematoma and neurological dysfunctions were assessed in mice continuously until 35 days after ICH. In addition, demyelination, electrophysiology and neuroinflammation were evaluated. Furthermore, the mechanisms of microglial regulation by SIRPα-v Exos were investigated in vitro under coculture conditions. RESULTS: The results demonstrated that the clearance of hematoma in mice suffering from ICH was accelerated after SIRPα-v Exo treatment. SIRPα-v Exos improved long-term neurological dysfunction by ameliorating white matter injury. In addition, SIRPα-v Exos recruited regulatory T cells (Tregs) to promote M2 polarization of microglia/macrophages in the peri-hematoma tissue. In vitro experiments further showed that SIRPα-v Exos regulated primary microglia in a direct and indirect manner in synergy with Tregs. CONCLUSION: Our studies revealed that SIRPα-v Exos could accelerate the clearance of hematoma and ameliorate secondary white matter injury after ICH through regulation of microglia/macrophages. SIRPα-v Exos may become a promising treatment for ICH in clinical practice.
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BACKGROUND: Chronic cerebral hypoperfusion (CCH) underlies secondary brain injury following certain metabolic disorders and central nervous system (CNS) diseases. Dysregulation of the microbiota-gut-brain axis can exacerbate various CNS disorders through aberrantly expressed metabolites such as short-chain fatty acids (SCFAs). Yet, its relationship with CCH remains to be demonstrated. And if so, it is of interest to explore whether restoring gut microbiota to maintain SCFA metabolism could protect against CCH. RESULTS: Rats subjected to bilateral common carotid artery occlusion (BCCAO) as a model of CCH exhibited cognitive impairment, depressive-like behaviors, decreased gut motility, and compromised gut barrier functions. The 16S ribosomal RNA gene sequencing revealed an abnormal gut microbiota profile and decreased relative abundance of some representative SCFA producers, with the decreased hippocampal SCFAs as the further evidence. Using fecal microbiota transplantation (FMT), rats recolonized with a balanced gut microbiome acquired a higher level of hippocampal SCFAs, as well as decreased neuroinflammation when exposed to lipopolysaccharide. Healthy FMT promoted gut motility and gut barrier functions, and improved cognitive decline and depressive-like behaviors by inhibiting hippocampal neuronal apoptosis in BCCAO rats. Long-term SCFA supplementation further confirmed its neuroprotective effect in terms of relieving inflammatory response and hippocampal neuronal apoptosis following BCCAO. CONCLUSION: Our results demonstrate that modulating the gut microbiome via FMT can ameliorate BCCAO-induced gut dysbiosis, cognitive decline, and depressive-like behaviors, possibly by enhancing the relative abundance of SCFA-producing floras and subsequently increasing SCFA levels. Video abstract.
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Eje Cerebro-Intestino , Microbioma Gastrointestinal , Animales , Ácidos Grasos Volátiles/metabolismo , Trasplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/fisiología , Ratones Endogámicos C57BL , RatasRESUMEN
Neuroinflammation is a major reason for white matter injury (WMI) after intracerebral hemorrhage (ICH). Apart from microglia/macrophage activation, T cells also play an important role in regulating immune responses after ICH. In a previous study, we have revealed the role of minocycline in modulating microglia/macrophage activation after ICH. However, the exact mechanisms of minocycline in regulating T cells differentiation after ICH are still not well understood. Hence, this study explored the relationship between minocycline and CD4+ T cell differentiation after ICH. Piglet ICH model was used to investigate naive CD4+ T cell differentiation and T cells signal gene activation after ICH with immunofluorescence and whole transcriptome sequencing. Naive CD4+ T cells and primary oligodendrocyte coculture model were established to explore the effect and mechanism of minocycline in modulating CD4+ T cell differentiation after ICH. Flow cytometry was used to indicate CD4+ T cell differentiation after ICH. The mechanism of minocycline in modulating CD4+ T cell differentiation was demonstrated with immunofluorescence and western blot. Double immunostaining of representative CD4+ T cell marker CD3 and different subtype CD4+ T cell assisted proteins (IL17, IL4, Foxp3, and IFNγ) demonstrated naive CD4+ T cell differentiation in piglet after ICH. Whole transcriptome sequencing for perihematomal white matter sorted from piglet brains indicated T cell signal gene activation after ICH. The results of luxol fast blue staining, immunofluorescent staining, and electron microscopy showed that minocycline alleviated white matter injury after ICH in piglets. For our in vitro model, minocycline reduced oligodendrocyte injury and neuroinflammation by regulating CD4+ T cell differentiation after ICH. Moreover, minocycline increased the expression of NOTCH1, ACT1, RBP-J, and NICD1 in cultured CD4+ T cell when stimulated with hemoglobin. Hence, minocycline treatment could modulate naive CD4+ T cell differentiation and attenuate white matter injury via regulating Notch1 signaling pathway after ICH.
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Lesiones Encefálicas , Sustancia Blanca , Animales , Lesiones Encefálicas/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Diferenciación Celular , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Microglía/metabolismo , Minociclina/farmacología , Minociclina/uso terapéutico , Transducción de Señal , Porcinos , Sustancia Blanca/metabolismoRESUMEN
Cerebral hemodynamic dysfunction and hypoperfusion have been found to underlie vascular depression, but whether the gut-brain axis is involved remains unknown. In this study, a rat model of bilateral common carotid artery occlusion (BCCAO) was adopted to mimic chronic cerebral hypoperfusion. A reduced sucrose preference ratio, increased immobility time in the tail suspension test and forced swim test, and compromised gut homeostasis were found. A promoted conversion of tryptophan (Trp) into kynurenine (Kyn) instead of 5-hydroxytryptamine (5-HT) was observed in the hippocampus and gut of BCCAO rats. Meanwhile, 16S ribosomal RNA gene sequencing suggested a compromised profile of the gut SCFA-producing microbiome, with a decreased serum level of SCFAs revealed by targeted metabolomics analysis. With SCFA supplementation, BCCAO rats exhibited ameliorated depressive-like behaviors and improved gut dysbiosis, compared with the salt-matched BCCAO group. Enzyme-linked immunosorbent assays and quantitative RT-PCR suggested that SCFA supplementation suppressed the conversion of Trp to Kyn and rescued the reduction in 5-HT levels in the hippocampus and gut. In addition to inhibiting the upregulation of inflammatory cytokines, SCFA supplementation ameliorated the activated oxidative stress and reduced the number of microglia and the expression of its proinflammatory markers in the hippocampus post BCCAO. In conclusion, our data suggested the participation of the gut-brain axis in vascular depression, shedding light on the neuroprotective potential of treatment with gut-derived SCFAs.
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Triptófano , Depresión Vascular , Animales , Eje Cerebro-Intestino , Citocinas/metabolismo , Depresión/tratamiento farmacológico , Depresión/metabolismo , Ácidos Grasos Volátiles , Quinurenina/metabolismo , Ratas , Serotonina/metabolismo , Sacarosa , Triptófano/metabolismoRESUMEN
Moyamoya disease (MMD) is a chronic cerebrovascular disease characterized by progressive stenosis of the arteries of the circle of Willis, with the formation of collateral vascular network at the base of the brain. Its clinical manifestations are complicated. Numerous studies have attempted to clarify the clinical features of MMD, including its epidemiology, genetic characteristics, and pathophysiology. With the development of neuroimaging techniques, various neuroimaging modalities with different advantages have deepened the understanding of MMD in terms of structural, functional, spatial, and temporal dimensions. At present, the main treatment for MMD focuses on neurological protection, cerebral blood flow reconstruction, and neurological rehabilitation, such as pharmacological treatment, surgical revascularization, and cognitive rehabilitation. In this review, we discuss recent progress in understanding the clinical features, in the neuroimaging evaluation and treatment of MMD.
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Enfermedad de Moyamoya , Encéfalo/diagnóstico por imagen , Progresión de la Enfermedad , Humanos , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/genética , Enfermedad de Moyamoya/terapia , NeuroimagenRESUMEN
OBJECTIVE: Postoperative complications of surgical revascularization in moyamoya disease (MMD) are difficult to predict because of poor knowledge of the underlying pathophysiological process. Since the aim of surgery is to improve brain dynamics by increasing regional blood flow, we hypothesize that postoperative complications are closely related to aberrant electrophysiological changes. Thus, we evaluated the clinical significance of intraoperative electrocorticography (iECoG) in bypass surgery for adult MMD. METHODS: Ninety-one adult patients operated on by the same neurosurgeon in our institute were involved (26 in the iECoG group, 65 in the traditional group). Two 1 × 6 subdural electrode grids were placed parallel to the middle frontal gyrus and superior temporal gyrus to record ECoG data continuously during the procedure in the iECoG group. Selected from several M4 candidate arteries, the recipient artery was determined to be closer to the cortex with lower power spectral density (PSD) in the beta band. The PSD parameter we used was the (delta+theta)/(alpha+beta) (DTAB) ratio (DTABR). Next, the pre- and post-bypass PSD values were evaluated, and correlations between post-/pre-bypass PSD parameter ratios and neurological/neuropsychological performance (in terms of changes in National Institutes of Health Stroke Scale [NIHSS] and Mini-Mental State Examination [MMSE] scores) were analyzed. RESULTS: Postoperative complications (transient neurological events) in the iECoG group were significantly lower than those in the traditional group (p = 0.046). In the iECoG group, the post-/pre-bypass DTABR ratio in the bypass area was significantly correlated with postoperative NIHSS (p = 0.002, r2 = 0.338) and MMSE changes (p = 0.007, r2 = 0.266). In the nonbypass area, neither postoperative NIHSS nor MMSE changes showed a significant correlation with the post-/pre-bypass DTABR ratio (p > 0.05). Additionally, patients with postoperative complications exhibited significantly higher DTABR (1.67 ± 0.33 vs. 0.95 ± 0.08, p = 0.003) and PSD of the theta band (1.54 ± 0.21 vs. 1.13 ± 0.08, p = 0.036). CONCLUSIONS: This study is the first to explain and guide surgical revascularization from the perspective of electrophysiology. Intraoperative ECoG is not only sensitive in reflecting and predicting postoperative neurological and cognitive performance but also usable as a reference for recipient artery selection.