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Abstract Substance use disorders (SUDs) imposes profound physical, psychological, and socioeconomic burdens on individuals, families, communities, and society as a whole, but the available treatment options remain limited. Deep brain-machine interfaces (DBMIs) provide an innovative approach by facilitating efficient interactions between external devices and deep brain structures, thereby enabling the meticulous monitoring and precise modulation of neural activity in these regions. This pioneering paradigm holds significant promise for revolutionizing the treatment landscape of addictive disorders. In this review, we carefully examine the potential of closed-loop DBMIs for addressing SUDs, with a specific emphasis on three fundamental aspects: addictive behaviors-related biomarkers, neuromodulation techniques, and control policies. Although direct empirical evidence is still somewhat limited, rapid advancements in cutting-edge technologies such as electrophysiological and neurochemical recordings, deep brain stimulation, optogenetics, microfluidics, and control theory offer fertile ground for exploring the transformative potential of closed-loop DBMIs for ameliorating symptoms and enhancing the overall well-being of individuals struggling with SUDs.

Abstract The use of anticoagulants has become more frequent due to the progressive aging population and increased thromboembolic events. Consequently, the proportion of anticoagulant-associated intracerebral hemorrhage (AAICH) in stroke patients is gradually increasing. Compared with intracerebral hemorrhage (ICH) patients without coagulopathy, patients with AAICH may have larger hematomas, worse prognoses, and higher mortality. Given the need for anticoagulant reversal and resumption, the management of AAICH differs from that of conventional medical or surgical treatments for ICH, and it is more specific. Understanding the pharmacology of anticoagulants and identifying agents that can reverse their effects in the early stages are crucial for treating life-threatening AAICH. When patients transition beyond the acute phase and their vital signs stabilize, it is important to consider resuming anticoagulants at the right time to prevent the occurrence of further thromboembolism. However, the timing and strategy for reversing and resuming anticoagulants are still in a dilemma. Herein, we summarize the important clinical studies, reviews, and related guidelines published in the past few years that focus on the reversal and resumption of anticoagulants in AAICH patients to help implement decisive diagnosis and treatment strategies in the clinical setting.

Chronic cerebral artery occlusion is an important cause of ischemic stroke, resulting in up to 45% of all ischemic strokes. Therefore, treatment of chronic cerebral artery occlusion is critical to improve outcomes in effected patients. In the past, treatment of chronic cerebral artery occlusion focused on drugs and surgical bypass, but effectiveness and potential benefits are not well-supported. In recent years, endovascular recanalization therapy has become more prominent as a treatment for chronic cerebral artery occlusion, due to advances in endovascular procedures, experience and equipment, as well as more advanced imaging methods. Small clinical studies have shown that interventional therapy for chronic cerebral artery occlusions may be safe and effective, yet, there is still a lack of uniform guidelines. This review discusses the current support for recanalization of chronic intracranial large vessel occlusion.

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations (microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

Stroke, a cerebrovascular disease with a high mortality rate, is categorized as either ischemic or hemorrhagic. Current existing therapies have limitations, including a narrow time window for treatment. As stroke induces a rapid and large immune response, immune cells and inflammatory mediators have become promising therapeutic targets for both ischemic and hemorrhagic strokes. In recent years, T cells have been investigated for their role in the pathogenesis of secondary injury and their therapeutic potential after stroke. And regulatory T cells, as one of the subpopulations of T cells, have been proved neuroprotective at both acute and recovery stages. In this review, we summarize the existing roles of Tregs in stroke and the various methods available for Treg intervention, and then provide a perspective for the future of immunotherapy in stroke.

Sixty-three patients admitted to 5 hospitals in 2014–2020 for the treatment of severe hypertensive brainstem hemorrhage by CT-guided and bone marker-oriented transcerebellar aspiration were enrolled in this study. The puncture accuracy, duration of hematoma removal, tracheal decannulation, postoperative complications, postoperative consciousness recovery time, Glasgow Outcome Scale (GOS) score, and prognosis outcome at follow-up were retrospectively analyzed. Additionally, the relationship between admission Glasgow Coma Scale (GCS) score and GOS score, and between hematoma volume and prognosis of patients was analyzed at follow-up. Results showed that CT localization–based and bone marker oriented transcerebellar hematoma aspiration in the treatment of severe hypertensive brainstem hemorrhage ensures high puncture accuracy, relatively low surgery risk, and good prognosis. The prognosis relates to the state of consciousness and hematoma volume.

Abstract Due to the limited capacity of the adult mammalian brain to self-repair and regenerate, neurological diseases, especially neurodegenerative disorders and stroke, characterized by irreversible cellular damage are often considered as refractory diseases. Neural stem cells (NSCs) play a unique role in the treatment of neurological diseases for their abilities to self-renew and form different neural lineage cells, such as neurons and glial cells. With the increasing understanding of neurodevelopment and advances in stem cell technology, NSCs can be obtained from different sources and directed to differentiate into a specific neural lineage cell phenotype purposefully, making it possible to replace specific cells lost in some neurological diseases, which provides new approaches to treat neurodegenerative diseases as well as stroke. In this review, we outline the advances in generating several neuronal lineage subtypes from different sources of NSCs. We further summarize the therapeutic effects and possible therapeutic mechanisms of these fated specific NSCs in neurological disease models, with special emphasis on Parkinson’s disease and ischemic stroke. Finally, from the perspective of clinical translation, we compare the strengths and weaknesses of different sources of NSCs and different methods of directed differentiation, and propose future research directions for directed differentiation of NSCs in regenerative medicine.

Objective: To observe the effect of intra-hematoma Rosiglitazone (RSG) infusion therapy in treating intracerebral hemorrhage (ICH). Specifically, to explore the effects of RSG on tight junction associated proteins Occludin and ZO-1 expression within perihematomal brain tissues as well as the blood–brain barrier (BBB) permeability after ICH in rabbits. Methods: A total of 30 rabbits were randomly assigned to three groups including sham control group (NC group, n = 10), hemorrhage model group (HM group, n = 10), and hemorrhage model with RSG treatment group (RSG group, n = 10). ICH was induced in rabbits of HM group and RSG group, involving an injection of autologous non-anticoagulant artery blood (0.3 mL, similar to basal ganglia hematoma 30 mL in humans) into the left basal ganglia of the rabbits’ brains. The NC group was injected with the same amount of saline into the same area. Six hours later after ICH induction or sham surgery, the RSG group received the intra-hematoma RSG (0.5 mg/0.1 mL) infusion, meanwhile the NC group and the HM group were injected with saline (0.1 mL) into the hematoma area. On day seven, the perihematomal brain tissues were obtained to determine the Occludin and ZO-1 expressions by Western Blot and RT-PCR, and the BBB permeability by the Evan’ s Blue (EB) content. Results: Occludin and ZO-1 expressions and mRNA levels were all significantly decreased in the HM group and RSG group compared with the NC group (P

Abstract. Background:. To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19. Methods:. This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable. Results:. A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%–48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151–3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350–67.410, P 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions:. SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events. Trial registration:. Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1

Summary: Glioblastoma (GBM) is the most common form of malignant primary brain tumor with a dismal prognosis. Currently, the standard treatments for GBM rarely achieve satisfactory results, which means that current treatments are not individualized and precise enough. In this study, a multiomics-based GBM classification was established and three subclasses (GPA, GPB, and GPC) were identified, which have different molecular features both in bulk samples and at single-cell resolution. A robust GBM poor prognostic signature (GPS) score model was then developed using machine learning method, manifesting an excellent ability to predict the survival of GBM. NVP−BEZ235, GDC−0980, dasatinib and XL765 were ultimately identified to have subclass-specific efficacy targeting patients with a high risk of poor prognosis. Furthermore, the GBM classification and GPS score model could be considered as potential biomarkers for immunotherapy response. In summary, an integrative genomic analysis was conducted to advance individual-based therapies in GBM.

The 17th National Annual Conference on Neurological Infectious Diseases and Cerebrospinal Fluid Cytology of the Chinese Medical Association Neurology Branch was successfully held in Wuhan, Hubei, China. During the conference, many well-known neurology experts in China conducted in-depth and detailed discussions on the research progress of infectious diseases of the nervous system and cerebrospinal fluid cytology, which benefited the participants a lot.

The lack of regenerative capacity of neurons leads to poor prognoses for some neurological disorders. The use of small molecules to directly reprogram somatic cells into neurons provides a new therapeutic strategy for neurological diseases. In this review, the mechanisms of action of different small molecules, the approaches to screening small molecule cocktails, and the methods employed to detect their reprogramming efficiency are discussed, and the studies, focusing on neuronal reprogramming using small molecules in neurological disease models, are collected. Future research efforts are needed to investigate the in vivo mechanisms of small molecule-mediated neuronal reprogramming under pathophysiological states, optimize screening cocktails and dosing regimens, and identify safe and effective delivery routes to promote neural regeneration in different neurological diseases.

Intracerebral hemorrhage (ICH) is the most disabling form of stroke, but effective treatment protocols for ICH are still limited. The minimally invasive surgery (MIS) is a potential and effective treatment for ICH in recent years. However, it is associated with a risk of rebleeding. This review aims to discuss some key facts about rebleeding, such as thrombolytic agents, therapeutic time window, and first aspiration volume.

Spontaneous intracerebral hemorrhage (ICH), a devastating neurological emergency, is characterized by a high mortality and mobility due to cerebrovascular rupture and hematoma formation. Here we describe a 52-year-old woman with a 34 ml left external capsule hemorrhage who developed unconsciousness and right hemiplegia. Minimally invasive puncture was subsequently performed followed by thrombolysis therapy for hematoma evacuation. At day 4 after symptom onset, surgery for hematoma evacuation was performed. Specifically, CT imaging was utilized to establish a trajectory for the YL-1 type puncture needle. Once access was established, the hematoma was evacuated through thrombolysis and drainage. After the clot was evacuated, the patient achieved a favorable outcome. The successful outcome achieved in this specific case, suggests that minimally invasive puncture and thrombolysis after intracerebral hemorrhage may be a promising treatment option for hematoma evacuation.

Brainstem hemorrhage (mainly pontine hemorrhage caused by hypertension) has the clinical characteristics of acute onset, rapid progress, high mortality, and high disability rate. Due to the complexity of the brainstem’s anatomical structure and functional importance, it is generally recognized that brainstem treatment is difficult and risky, so it has been regarded as a restricted area of surgery. However, in recent years, continuous progress is being made in many areas, including microsurgical technology, stereotactic technology, robot-assisted surgery, neuroendoscopy, and theoretical and clinical practice of neurorestoration, aiding in the understanding, diagnosis, and treatment of brainstem hemorrhage injuries. The Chinese Association of Neurorestoratology (CANR; Preparatory) and the China Committee of International Association of Neurorestoratology (IANR-China Committee) organized relevant experts to formulate this clinical guideline to diagnose and restore damaged nerves after brainstem hemorrhages, promote a standardized diagnosis, and to neurorestoratologically treat this disease.

Minimally invasive surgery has been widely used in the treatment of patients with intracerebral hemorrhage in recent years, and has achieved good clinical efficacy. Based on the basic theory of minimally invasive surgery, indications and contraindications are discussed, and then the minimally invasive preoperative preparation, intraoperative operation, postoperative management, and other aspects are systematically discussed. Finally, the application of microsurgery in the precise treatment of intracerebral hemorrhage is further prospected.

Myelin oligodendrocyte glycoprotein-IgG-associated disorder (MOGAD) is a nervous system (NS) demyelination disease and a newly recognized distinct disease complicated with various diseases or symptoms; however, MOGAD was once considered a subset of neuromyelitis optica spectrum disorder (NMOSD). The detection of MOG-IgG has been greatly improved by the cell-based assay test method. In one study, 31% of NMOSD patients with negative aquaporin-4 (AQP-4) antibody were MOG-IgG positive. MOGAD occurs in approximately the fourth decade of a person’s life without a markedly female predominance. Usually, optic neuritis (ON), myelitis or acute disseminated encephalomyelitis (ADEM) encephalitis are the typical symptoms of MOGAD. MOG-IgG have been found in patients with peripheral neuropathy, teratoma, COVID-19 pneumonia, etc. Some studies have revealed the presence of brainstem lesions, encephalopathy or cortical encephalitis. Attention should be given to screening patients with atypical symptoms. Compared to NMOSD, MOGAD generally responds well to immunotherapy and has a good functional prognosis. Approximately 44-83% of patients undergo relapsing episodes within 8 months, which mostly involve the optic nerve, and persistently observed MOG-IgG and severe clinical performance may indicate a polyphasic course of illness. Currently, there is a lack of clinical randomized controlled trials on the treatment and prognosis of MOGAD. The purpose of this review is to discuss the clinical manifestations, imaging features, outcomes and prognosis of MOGAD.

Objective: The main aims of the study were to explore the correlation between different times of a minimally invasive operation and perihaematomal oedema properties in patients with cerebral hemorrhage, to identify the optimal time window for a minimally invasive operation and to observe the effect of different doses of urokinase on perihaematomal oedema properties. Methods: A retrospective analysis was performed on 95 patients with cerebral hemorrhage who were treated in the Department of Neurology at the Tianmen First People’s Hospital between April 2014 and December 2017. Finally, 66 valid cases were included, and they were divided into three groups according to the time from onset to the minimally invasive operation. Haematoma volume and oedema volume before the surgery, 4 days after the surgery and 14 days after the surgery were compared among the three groups. Results: There was no significant difference in postoperative oedema volume among the three groups. The difference in haematoma volume among the three groups may be related to haematoma absorption after a long period of time. There was no significant linear correlation between the timing of surgery and the dosage of urokinase or the perihaematomal oedema volume in the three groups. There was no significant difference in the rebleeding rate and pulmonary infection complication rate among the three groups. Conclusions: The operation timing of minimally invasive puncture haematoma removal in patients with cerebral hemorrhage has no obvious influence on perihaematomal oedema, rebleeding and pulmonary infection complications. This study has limitations, and a prospective cohort study with a larger sample size is needed to explore the details, such as patient selection and the timing of minimally invasive surgery.

Stroke is the second leading cause of death worldwide. Therefore, research on prevention and treatment for stroke has great significance. In recent years, the development of artificial intelligence (AI) technology has brought new hopes to healthcare. The resulting partnerships between clinicians and computation science scientists, supported by growing strength of clinical informatics, are beginning to yield positive results. AI techniques have been used successfully in skin/cancer-related studies. Besides that, AI also have been used more and more in the field of stroke. In this review we summarized the application of artificial intelligence in the four main areas of stroke care: diagnosis, outcome prediction, treatment and rehabilitation. Finally, we look forward to the current studies of AI-assisted medical care and make some suggestions for the future potential development direction.

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high rates of mortality and morbidity. It induces cell death that is responsible for neurological deficits postinjury. There are no therapies that effectively mitigate cell death to treat ICH. This review aims to summarize our knowledge of ICH-induced cell death with a focus on apoptosis and necrosis. We also discuss the involvement of ICH in recently described modes of cell death including necroptosis, pyroptosis, ferroptosis, autophagy, and parthanatos. We summarize treatment strategies to mitigate brain injury based on particular cell death pathways after ICH.

Objectives: Intracranial hemorrhage is the second most common stroke subtype following ischemic stroke and usually induces high mortality and disability. Here, we conducted a retrospective study to establish a nomogram clinical prediction model. Methods: First, the baseline data of patients who presented to our hospital in 2015–2021 were collected and compared (789 patients for the training cohort and 378 patients for the validation cohort). Second, univariate and binary logistic analyses were performed to screen out alternative indicators. Finally, a clinical prediction model by nomogram was established that included such indicators to estimate the prognosis of intracranial hemorrhage patients. Results: Univariate logistic analysis was used to screen several possible impact factors, including hypertension, hematoma volume, Glasgow Coma Scale (GCS) score, intracranial hemorrhage (ICH) score, irregular shape, uneven density, intraventricular hemorrhage (IVH) relation, fibrinogen, D-dimer, low density lipoprotein (LDL), high-density lipoprotein (HDL), creatinine, total protein, hemoglobin (HB), white blood cell (WBC), neutrophil blood cell (NBC), lymphocyte blood cell (LBC), the neutrophil lymphocyte ratio (NLR), surgery, deep venous thrombosis (DVT) or pulmonary embolism (PE) rate, hospital day, and hypertension control. Further binary logistic analysis revealed that ICH score (p = 0.036), GCS score (p = 0.000), irregular shape (p = 0.000), uneven density (p = 0.002), IVH relation (p = 0.014), surgery (p = 0.000) were independent indicators to construct a nomogram clinical prediction model. The C statistic was 0.840. Conclusions: ICH score, GCS score, irregular shape, uneven density, IVH relation, surgery are easily available indicators to assist neurologists in formulating the most appropriate therapy for every intracranial hemorrhage patient. Further large prospective clinical trials are needed to obtain more integrated and reliable conclusions.

On September 27, 2021, the Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE) trial kick-off meeting was successfully held. During the online meeting, many member institutions from all over the country had together witnessed the successful launch of this trial. The STIPE trial is expected to support the safety and efficacy of surgical treatment for the patients with severe primary pontine hemorrhage.

Background: Over the past decade, many studies have reported the association of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with clinical outcome of intracerebral hemorrhage (ICH). However, a broad consensus has not been reached.Objective: To evaluate the role of BNP/NT-proBNP levels in prognosis and disease severity assessment in patients with ICH.Methods: A systematic literature search was conducted utilizing PubMed, Embase, Web of Science and the Cochrane Library databases up to July 23, 2021. Studies that explored the association between BNP/NT-proBNP level and clinical outcome or disease severity in ICH patients were eligible. Outcome measures were all-cause mortality, poor functional outcome, adverse cardiac events and markers of disease severity.Results: Ten studies, involving 1,373 patients with ICH, met the inclusion criteria. Nine studies focused on clinical outcomes (five all-cause mortality, five functional outcomes, and one adverse cardiac event) and seven on disease severity. In terms of prognosis, all five studies showed an association between elevated BNP/NT-proBNP level and increased risk of all-cause mortality in ICH patients. Four of the five studies reported poor functional outcomes in patients with higher BNP/NT-proBNP levels and one study associated higher BNP/NT-proBNP levels with increased risk of adverse cardiac events. Moreover, two studies identified an additional predictive ability of BNP/NT-proBNP level beyond that of pre-existing prognostic variables. In terms of disease severity, five studies (71%) reported that BNP/NT-proBNP level correlated positively with hematoma volume in addition to ICH and GCS scores.Conclusion: Elevated BNP/NT-proBNP level is associated with increased risk of all-cause mortality, poor functional outcome, adverse cardiac events and disease severity in patients with ICH. Thus, BNP/NT-proBNP level is a promising prognostic indicator for ICH and also an effective marker of disease severity. Current evidence remains limited by the small number and high heterogeneity of included studies. Further appropriately designed, large-scale studies are required to confirm the current findings.

The prognostic role and diagnostic ability of coronavirus disease 2019 (COVID-19) disease indicators are not elucidated, thus, the current study aimed to investigate the prognostic role and diagnostic ability of several COVID-19 disease indicators including the levels of oxygen saturation, leukocytes, lymphocytes, albumin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer in patients with COVID-19. The levels of oxygen saturation, lymphocytes, and albumin were significantly higher in the common and severe clinical type patients compared with those in critical type patients. However, levels of leukocytes, CRP, IL-6, and D-dimer were significantly lower in the common and severe type patients compared with those in critical type patients (P < 0.001). Moreover, the current study demonstrated that the seven indicators have good diagnostic and prognostic powers in patients with COVID-19. Furthermore, a two-indicator (CRP and D-dimer) prognostic signature in training and testing datasets was constructed and validated to better understand the prognostic role of the indicators in COVID-19 patients. The patients were classified into high-risk and low-risk groups based on the median-risk scores. The findings of the Kaplan–Meier curve analysis indicated a significant divergence between the high-risk and low-risk groups. The findings of the receiver operating curve (ROC) analysis indicated the good performance of the signature in the prognosis prediction of COVID-19. In addition, a nomogram was constructed to assist clinicians in developing clinical decision-making for COVID-19 patients. In conclusion, the findings of the current study demonstrated that the seven indicators are potential diagnostic markers for COVID-19 and a two-indicator prognostic signature identification may improve clinical management for COVID-19 patients.

Primary brainstem hemorrhage (PBSH) is the most fatal subtype of intracerebral hemorrhage and is invariably associated with poor prognosis. Several prognostic factors are involved, of which the two most predominant and consistent are the initial level of consciousness and hemorrhage size. Other predictors, such as age, hyperthermia, and hydrocephalus, are generally not dependable indicators for making prognoses. Scoring systems have now been developed that can predict mortality and functional outcomes in patients suffering from PBSH, which can thus guide treatment decision-making. A novel grading scale, entitled “the new primary pontine hemorrhage (PPH) score,” represents the latest approach in scoring systems. In this system, patients with a score of 2–3 points appear to benefit from surgical management, although this claim requires further verification. The four main surgical options for the treatment of PBSH are craniotomy, stereotactic hematoma puncture and drainage, endoscopic hematoma removal, and external ventricular drainage. Nevertheless, the management of PBSH still primarily involves conservative treatment methods and surgery is generally not recommended, according to current practice. However, the ongoing clinical trial, entitled Safety and Efficacy of Surgical Treatment in Severe Primary Pontine Hemorrhage Evacuation (STIPE), should provide additional evidence to support the surgical treatment of PBSH. Therefore, we advocate the update of epidemiological data and re-evaluation of PBSH treatment in a contemporary context.

Transient ischemic attack (TIA) has been widely regarded as a clinical entity. Even though magnetic resonance imaging (MRI) results of TIA patients are negative, potential neurovascular damage might be present, and may account for long-term cognitive impairment. Animal models that simulate human diseases are essential tools for in-depth study of TIA. Previous studies have clarified that Dl-3-N-butylphthalide (NBP) promotes angiogenesis after stroke. However, the effects of NBP on TIA remain unknown. This study aims to develop an optimized TIA model in C57BL/6 mice to explore the microscopic evidence of ischemic injury after TIA, and investigate the therapeutic effects of NBP on TIA. C57BL/6 mice underwent varying durations (7, 8, 9 or 10 min) of middle cerebral artery occlusion (MCAO). Cerebral artery occlusion and reperfusion were assessed by laser speckle contrast imaging. TIA and ischemic stroke were distinguished by neurological testing and MRI examination at 24 h post-operation. Neuronal apoptosis was examined by TUNEL staining. Images of submicron cerebrovascular networks were obtained via micro-optical sectioning tomography. Subsequently, the mice were randomly assigned to a sham-operated group, a vehicle-treated TIA group or an NBP-treated TIA group. Vascular density was determined by immunofluorescent staining and fluorescein isothiocyanate method, and the expression of angiogenic growth factors were detected by western blot analysis. We found that an 8-min or shorter period of ischemia induced neither permanent neurological deficits nor MRI detectable brain lesions in C57BL/6 mice, but histologically caused neuronal apoptosis and cerebral vasculature abnormalities. NBP treatment increased the number of CD31+ microvessels and perfused microvessels after TIA. NBP also up-regulated the expression of VEGF, Ang-1 and Ang-2 and improved the cerebrovascular network. In conclusion, 8 min or shorter cerebral ischemia induced by the suture MCAO method is an appropriate TIA model in C57BL/6 mice, which conforms to the definition of human TIA, but causes microscopic neurovascular impairment. NBP treatment increased the expression of angiogenic growth factors, promoted angiogenesis and improved cerebral microvessels after TIA. Our study provides new insights on the pathogenesis and potential treatments of TIA.

We describe a unique case in which a patient was initially diagnosed with meningoencephalitis and then detected anti-myelin oligodendrocyte glycoprotein (MOG) antibody and demyelinating brain lesions. A 43-year-old Chinese man who complained of headache and fever, was diagnosed with meningoencephalitis after cerebrospinal fluid (CSF) analysis. One month after onset, brain imaging revealed multiple lesions in bilateral white matter, and the anti-MOG antibody was detected in his serum and CSF (titer is 1:32 and 1:10, respectively). After a 3-month glucocorticoid therapy, repeated brain imaging and serological analysis for anti-MOG antibodies showed significant improvement. Multiple intracranial demyelinating lesions secondary to meningoencephalitis may be accompanied by anti-MOG antibody positivity, which can be reversed by hormone therapy.

In November 2021, the project of “Multi-sensor fusion and intelligent aspiration control of minimally invasive surgical robot for intracerebral hemorrhage” has been successfully supported by the National Natural Science Foundation of China (NSFC). Professor Zhouping Tang, a neurologist from Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology in Wuhan China will lead this project of ¥2,400,000 in the next four years. Team led by Professor Zhouping Tang will work with team led by Professor Bo Tao from School of Mechanical Science & Engineering, Huazhong University of Science and Technology, team led by Professor Dansheng Chen from School of Mechanical Engineering & Automation-BUAA, Beihang University and team led by engineer Wenjie Liu from Beijing WanTeFu Medical Instrument Co., Ltd to carry out fundamental investigations of micro-invasive treatment using Coexisting-Cooperative-Cognitive Robots (Tri-Co Robots).

Since mass effect and secondary brain injuries persist in the pathogenesis of intracerebral hemorrhage, hematoma evacuation within a limited time is reasonable. However, it is complex to define an accurate therapeutic time window (TTW) for hematoma evacuation. In this review, studies about TTW were discussed from four aspects: histopathology, molecular pathophysiology, neuroimaging and clinical outcomes. Animal experiments indicated that 6–12 h is the pathophysiological TTW of minimally invasive surgery. Clinical trials suggested that there is a correlation between TTW and clinical outcomes, while the exact TTW is still unclear due to lack of sufficient clinical studies, which deserves further investigation.

Background: Moyamoya angiopathy (MMA), which includes moyamoya disease (MMD) and moyamoya syndrome (MMS), is an uncommon cerebrovascular condition characterized by recurrent stroke. We carried out a bibliometric analysis to examine the development of and research trends in MMA research.Methods: Studies published between 2010 and 2019 on MMA were retrieved from the Web of Science Core Collection (WoSCC) on August 14, 2020, and bibliometric and visualization-based analyses were performed by using three different scientometric tools: HistCite, VOSviewer, and CiteSpace.Results: A total of 1,896 publications published in 384 journals by 6,744 authors, 1,641 institutions and 56 countries/regions were included in the analyses. Annual publication outputs increased from 2010 to 2019. The USA, Japan and China were three key contributors to this study field. Capital Medical University, Seoul National University, and Stanford University were three major institutions with larger numbers of publications. Zhang D, World Neurosurgery, Kuroda S, and STROKE were the most prolific author, prolific journal, top co-cited author and top co-cited journal, respectively. The top five keywords during this period were moyamoya disease, revascularization, stroke, children and surgery, while revascularization surgery and RNF213 were the most common frontier topics.Conclusions: In this study, the research trends of global scientific research on MMA over the past decade were systematically analyzed. The study can provide guidance for scholars who want to understand current trends in research in this area and new research frontiers.

Background: The coronavirus disease 2019 (COVID-19) has swept through the world at a tremendous speed, and there is still limited data available on the treatment for COVID-19. The mortality of severely and critically ill COVID-19 patients in the Optical Valley Branch of Tongji Hospital was low. We aimed to analyze the available treatment strategies to reduce mortality.Methods: In this retrospective, single-center study, we included 1,106 COVID-19 patients admitted to the Optical Valley Branch of Tongji Hospital from February 9 to March 9, 2020. Cases were analyzed for demographic and clinical features, laboratory data, and treatment methods. Outcomes were followed up until March 29, 2020.Results: Inflammation-related indices (hs-CRP, ESR, serum ferritin, and procalcitonin) were significantly higher in severe and critically ill patients than those in moderate patients. The levels of cytokines, including IL-6, IL2R, IL-8, and TNF-α, were also higher in the critical patients. Incidence of acute respiratory distress syndrome (ARDS) in the severely and critically ill group was 23.0% (99/431). Sixty-one patients underwent invasive mechanical ventilation. The correlation between SpO2/FiO2 and PaO2/FiO2 was confirmed, and the cut-off value of SpO2/FiO2 related to survival was 134.43. The mortality of patients with low SpO2/FiO2 (134.43) (72.7 vs. 33.3%). Among critical patients, the application rates of glucocorticoid therapy, continuous renal replacement therapy (CRRT), and anticoagulation treatment reached 55.2% (238/431), 7.2% (31/431), and 37.1% (160/431), respectively. Among the intubated patients, the application rates of glucocorticoid therapy, CRRT, and anticoagulation treatment were respectively 77.0% (47/61), 54.1% (33/61), and 98.4% (60/61).Conclusion: No vaccines or specific antiviral drugs for COVID-19 have been shown to be sufficiently safe and effective to date. Comprehensive treatment including ventilatory support, multiple organ function preservation, glucocorticoid use, renal replacement therapy, anticoagulation, and restrictive fluid management was the main treatment strategy. Early recognition and intervention, multidisciplinary collaboration, multi-organ function support, and personalized treatment might be the key for reducing mortality.

NCyborg Project, a new stroke rehabilitation pattern based on brain computer interface (BCI) and brain-inspired intelligent robots, is set up by Tongji Hospital and BrainCo. We will briefly introduce this project in this paper.

Risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is presumed to be high for neurologic intensive care unit (NICU) patients. However, exact incidences of VTE have yet to be reported. In this prospective observational study, we consecutively enrolled 126 neurocritical care patients who had an NICU stay ≥1 week with paralysis and/or unconsciousness. All patients received DVT prevention strategies. Patients were screened for VTE after 1 week of hospitalization, using venous ultrasonography and computed tomography pulmonary angiography. Following 1 week of NICU hospitalization, DVT incidence was 35.7% and PE incidence was 17.5%. Of the DVTs, 75.6% were in the muscular calf vein. Of the PEs, 22.7% were in main pulmonary arteries, while 77.3% were in branches. Approximately 96% of the DVTs and 86% of the PEs were asymptomatic. Approximately 24% of patients with DVT had a concurrent PE, while 50% of PE patients had a DVT. Paralysis, raised d -dimer on admission, and pulmonary infection were found to be independent risk factors for DVT. Paraplegia, femoral vein thrombosis, and pulmonary infection were found to be independent risk factors for PE. Despite active preventive measures, incidences of VTE in NICU patients were high. Most VTEs were asymptomatic, meaning they could have led to a missed diagnosis. Attention should be paid to the VTE events of critically ill neurological patients.

Stem cell therapy has emerged as a new promising therapeutic strategy for intracerebral hemorrhage (ICH). However, the efficiency of stem cell therapy is partially limited by low retention and engraftment of the delivered cells. Therefore, it’s necessary to improve the migration ability of stem cells to the injured area in order to save the costs and duration of cell preparation. This study aimed to investigate whether overexpression of CX3CR1, the specific receptor of chemokine fractalkine (FKN), in adipose-derived stem cells (ADSCs) can stimulate the cell migration to the injured area in the brain, improve functional recovery and protect against cell death following experimental ICH. ADSCs were isolated from subcutaneous adipose tissues of rats. ICH was induced by means of an injection of collagenase type VII. ELISA showed that the expression levels of fractalkine/FKN were increased at early time points, with a peak at day 3 after ICH. And it was found that different passages of ADSCs could express the chemokine receptor CX3CR1. Besides, the chemotactic movements of ADSCs toward fractalkine have been verified by transwell migration assay. ADSCs overexpressing CX3CR1 were established through lentivirus transfection. We found that after overexpression of CX3CR1 receptor, the migration ability of ADSCs was increased both in vitro and in vivo. In addition, reduced cell death and improved sensory and motor functions were seen in the mice ICH model. Thus, ADSCs overexpression CX3CR1 might be taken as a promising therapeutic strategy for the treatment of ICH.

Background: Schizophrenia is a severe psychiatric disorder with a high heritability. A single nucleotide polymorphism (SNP) rs1625579 (G/T; T is the common and presumed risk allele) within an intron of miR-137 gene has been recently suggested to contribute to the susceptibility to schizophrenia by a large-scale genome-wide association study (GWAS) in a sample of predominantly European ancestry. However, subsequent genetic association studies in Chinese population yielded inconsistent results. Methods: A meta-analysis reporting the association between rs1625579 and schizophrenia in Chinese population was carried out, pooling 4 eligible case–control studies involving 2847 patients and 3018 controls. Results: This meta-analysis demonstrated a significant association between rs1625579 and schizophrenia under the allele model [T versus G, odds ratio (OR):1.20, 95% confidence interval (CI): 1.06–1.36] and the recessive model (TT versus GT + GG; OR: 1.19; 95% CI: 1.04–1.37). Additionally, a marginal significant association under the additive model (TT versus GG; OR: 1.64; 95% CI: 1.00–2.69) was observed. However, no significant association was observed under the dominant model (TT + GT versus GG; OR: 1.58; 95% CI: 0.97–2.59). Conclusions: This meta-analysis suggested that the SNP rs1625579 in miR-137 gene might be involved in schizophrenia susceptibility in Chinese Han population.

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.

Diabetes mellitus is a widely spread chronic disease with growing incidence worldwide, and diabetic foot ulcer is one of the most serious complications of diabetes. Cellular therapy has shown promise in the management of diabetic foot ulcer in many preclinical experiments and clinical researches. Here, we performed a meta-analysis to evaluate the efficacy and safety of cellular therapy in the management of diabetic foot ulcer. We systematically searched PubMed, MEDLINE, EMBASE, and Cochrane Library databases from inception to May 2017 for randomized controlled trials assessing the efficacy of cellular therapy in diabetic foot ulcer, and a meta-analysis was conducted. A total of 6 randomized controlled clinical trials involving 241 individuals were included in this meta-analysis. The results suggested that cellular therapy could help accelerating the healing of diabetic foot ulcer, presented as higher ankle-brachial index (mean difference = 0.17, 95% confidence interval [CI] = 0.11 to 0.23), higher transcutaneous oxygen pressure (standardized mean difference [SMD] = 1.43; 95% CI, 1.09– to 1.78), higher ulcer healing rate (relative risk [RR] = 1.78; 95% CI, 1.41 to 2.25), higher amputation-free survival (RR = 1.25; 95% CI, 1.11 to 1.40), and lower scale of pain (SMD = −1.69; 95% CI, −2.05 to −1.33). Furthermore, cellular therapy seemed to be safe, with no serious complications and low risk of short-term slight complications. Cellular therapy could accelerate the rate of diabetic foot ulcer healing and may be more efficient than standard therapy for diabetic foot treatment.

In the central nervous system (CNS), the myelin sheath ensures efficient interconnection between neurons and contributes to the regulation of the proper function of neuronal networks. The maintenance of myelin and the well-organized subtle process of myelin plasticity requires cooperation among myelin-forming cells, glial cells, and neural networks. The process of cooperation is fragile, and the balance is highly susceptible to disruption by microenvironment influences. Reactive microglia play a critical and complicated role in the demyelination and remyelination process. Recent studies have shown that the voltage-gated proton channel Hv1 is selectively expressed in microglia in CNS, which regulates intracellular pH and is involved in the production of reactive oxygen species, underlying multifaceted roles in maintaining microglia function. This paper begins by examining the molecular mechanisms of demyelination and emphasizes the crucial role of the microenvironment in demyelination. It focuses specifically on the role of Hv1 in myelin repair and its therapeutic potential in CNS demyelinating diseases. [ABSTRACT FROM AUTHOR]

Hyperhomocysteinemia (HHcy) is independently associated with poorer long-term prognosis in patients with intracerebral haemorrhage (ICH); however, the effect and mechanisms of HHcy on ICH are still unclear. Here, we evaluated neurite outgrowth and neurological functional recovery using simulated models of ICH with HHcy in vitro and in vivo. We found that the neurite outgrowth velocity and motor functional recovery in the ICH plus HHcy group were significantly slower than that in the control group, indicating that homocysteine (Hcy) significantly impedes the neurite outgrowth recovery after ICH. Furthermore, phosphoproteomic data and signalome analysis of perihematomal brain tissues suggested that calmodulin-dependent protein kinases 2 (CAMK2A) kinase substrate pairs were significantly downregulated in ICH with HHcy compared with autologous blood injection only, both western blot and immunofluorescence staining confirmed this finding. Additionally, upregulation of pCAMK2A significantly increased neurite outgrowth recovery in ICH with HHcy. Collectively, we clarify the mechanism of HHcy-hindered neurite outgrowth recovery, and pCAMK2A may serve as a therapeutic strategy for promoting neurological recovery after ICH.