Senolytics and Senomorphics Targeting p38MAPK/NF-κB Pathway Protect Endothelial Cells from Oxidative Stress-Mediated Premature Senescence.

Oxidative stress is a prominent causal factor in the premature senescence of microvascular endothelial cells and the ensuing blood-brain barrier (BBB) dysfunction. Through the exposure of an in vitro model of human BBB, composed of brain microvascular endothelial cells (BMECs), astrocytes, and pericytes to H2O2, this study examined whether a specific targeting of the p38MAPK/NF-κB pathway and/or senescent cells could delay oxidative stress-mediated EC senescence and protect the BBB. Enlarged BMECs, displaying higher ß-galactosidase activity, γH2AX staining, p16 expression, and impaired tubulogenic capacity, were regarded as senescent. The BBB established with senescent BMECs had reduced transendothelial electrical resistance and increased paracellular flux, which are markers of BBB integrity and function, respectively. Premature senescence disrupted plasma-membrane localization of the tight junction protein, zonula occludens-1, and elevated basement membrane-degrading matrix metalloproteinase-2 activity and pro-inflammatory cytokine release. Inhibition of p38MAPK by BIRB796 and NF-κB by QNZ and the elimination of senescent cells by a combination of dasatinib and quercetin attenuated the effects of H2O2 on senescence markers; suppressed release of the pro-inflammatory cytokines interleukin-8, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1; restored tight junctional unity; and improved BBB function. In conclusion, therapeutic approaches that mitigate p38MAPK/NF-κB activity and senescent cell accumulation in the cerebrovasculature may successfully protect BBB from oxidative stress-induced BBB dysfunction.

Advancing stroke therapy: innovative approaches with stem cell-derived extracellular vesicles.

Stroke is a leading cause of mortality and long-term disability globally, with acute ischemic stroke (AIS) being the most common subtype. Despite significant advances in reperfusion therapies, their limited time window and associated risks underscore the necessity for novel treatment strategies. Stem cell-derived extracellular vesicles (EVs) have emerged as a promising therapeutic approach due to their ability to modulate the post-stroke microenvironment and facilitate neuroprotection and neurorestoration. This review synthesizes current research on the therapeutic potential of stem cell-derived EVs in AIS, focusing on their origin, biogenesis, mechanisms of action, and strategies for enhancing their targeting capacity and therapeutic efficacy. Additionally, we explore innovative combination therapies and discuss both the challenges and prospects of EV-based treatments. Our findings reveal that stem cell-derived EVs exhibit diverse therapeutic effects in AIS, such as promoting neuronal survival, diminishing neuroinflammation, protecting the blood-brain barrier, and enhancing angiogenesis and neurogenesis. Various strategies, including targeting modifications and cargo modifications, have been developed to improve the efficacy of EVs. Combining EVs with other treatments, such as reperfusion therapy, stem cell transplantation, nanomedicine, and gut microbiome modulation, holds great promise for improving stroke outcomes. However, challenges such as the heterogeneity of EVs and the need for standardized protocols for EV production and quality control remain to be addressed. Stem cell-derived EVs represent a novel therapeutic avenue for AIS, offering the potential to address the limitations of current treatments. Further research is needed to optimize EV-based therapies and translate their benefits to clinical practice, with an emphasis on ensuring safety, overcoming regulatory hurdles, and enhancing the specificity and efficacy of EV delivery to target tissues.

Hyperglycaemia perturbs blood-brain barrier integrity through its effects on endothelial cell characteristics and function.

Breakdown of blood-brain barrier (BBB) represents a key pathology in hyperglycemia-mediated cerebrovascular damage after an ischemic stroke. As changes in the level and nature of vasoactive agents released by endothelial cells (ECs) may contribute to BBB dysfunction, this study first explored the specific impact of hyperglycemia on EC characteristics and secretome. It then assessed whether secretome obtained from ECs subjected to normoglycaemia or hyperglycemia might regulate pericytic cytokine profile differently. Using a triple cell culture model of human BBB, composed of brain microvascular EC (BMEC), astrocytes and pericytes, this study showed that exposure to hyperglycemia (25 mM D-glucose) for 72 h impaired the BBB integrity and function as evidenced by decreases in transendothelial electrical resistance and increases in paracellular flux of sodium fluorescein. Dissolution of zonula occludens-1, a tight junction protein, and appearance of stress fibers appeared to play a key role in this pathology. Despite elevations in angiogenin, endothelin-1, interleukin-8 and basic fibroblast growth factor levels and a decrease in placental growth factor levels in BMEC subjected to hyperglycemia vs normoglycaemia (5.5 mM D-glucose), tubulogenic capacity of BMECs remained similar in both settings. Similarly, pericytes subjected to secretome obtained from hyperglycemic BMEC released higher quantities of macrophage migration inhibitory factor and serpin and lower quantities of monocyte chemoattractant protein-1, intercellular adhesion molecule, interleukin-6 and interleukin-8. Taken together these findings indicate the complexity of the mechanisms leading to BBB disruption in hyperglycemic settings and emphasize the importance of endothelial cell-pericyte axis in the development of novel therapeutic strategies.

The Role of Stem Cells as Therapeutics for Ischaemic Stroke.

Stroke remains one of the leading causes of death and disability worldwide. Current reperfusion treatments for ischaemic stroke are limited due to their narrow therapeutic window in rescuing ischaemic penumbra. Stem cell therapy offers a promising alternative. As a regenerative medicine, stem cells offer a wider range of treatment strategies, including long-term intervention for chronic patients, through the reparation and replacement of injured cells via mechanisms of differentiation and proliferation. The purpose of this review is to evaluate the therapeutic role of stem cells for ischaemic stroke. This paper discusses the pathology during acute, subacute, and chronic phases of cerebral ischaemic injury, highlights the mechanisms involved in mesenchymal, endothelial, haematopoietic, and neural stem cell-mediated cerebrovascular regeneration, and evaluates the pre-clinical and clinical data concerning the safety and efficacy of stem cell-based treatments. The treatment of stroke patients with different types of stem cells appears to be safe and efficacious even at relatively higher concentrations irrespective of the route and timing of administration. The priming or pre-conditioning of cells prior to administration appears to help augment their therapeutic impact. However, larger patient cohorts and later-phase trials are required to consolidate these findings.

Vascular Ageing: Mechanisms, Risk Factors, and Treatment Strategies.

Ageing constitutes the biggest risk factor for poor health and adversely affects the integrity and function of all the cells, tissues, and organs in the human body. Vascular ageing, characterised by vascular stiffness, endothelial dysfunction, increased oxidative stress, chronic low-grade inflammation, and early-stage atherosclerosis, may trigger or exacerbate the development of age-related vascular diseases, which each year contribute to more than 3.8 million deaths in Europe alone and necessitate a better understanding of the mechanisms involved. To this end, a large number of recent preclinical and clinical studies have focused on the exponential accumulation of senescent cells in the vascular system and paid particular attention to the specific roles of senescence-associated secretory phenotype, proteostasis dysfunction, age-mediated modulation of certain microRNA (miRNAs), and the contribution of other major vascular risk factors, notably diabetes, hypertension, or smoking, to vascular ageing in the elderly. The data generated paved the way for the development of various senotherapeutic interventions, ranging from the application of synthetic or natural senolytics and senomorphics to attempt to modify lifestyle, control diet, and restrict calorie intake. However, specific guidelines, considering the severity and characteristics of vascular ageing, need to be established before widespread use of these agents. This review briefly discusses the molecular and cellular mechanisms of vascular ageing and summarises the efficacy of widely studied senotherapeutics in the context of vascular ageing.

Delay of endothelial cell senescence protects cerebral barrier against age-related dysfunction: role of senolytics and senomorphics.

Accumulation of senescent cells in cerebrovasculature is thought to play an important role in age-related disruption of blood-brain barrier (BBB). Using an in vitro model of human BBB, composed of brain microvascular endothelial cells (BMECs), astrocytes and pericytes, this study explored the so-called correlative link between BMEC senescence and the BBB dysfunction in the absence or presence of functionally distinct senotherapeutics. Replicative senescence was deemed present at passage ≥19 where BMECs displayed shortened telomere length, reduced proliferative and tubulogenic potentials and increased NADPH oxidase activity, superoxide anion production (markers of oxidative stress), S-ß-galactosidase activity and γ-H2AX staining. Significant impairments observed in integrity and function of a model of BBB established with senescent BMECs, ascertained successively by decreases in transendothelial electrical resistance and increases in paracellular flux, revealed a close correlation between endothelial cell senescence and BBB dysfunction. Disruptions in the localization or expression of tight junction proteins, zonula occludens-1, occludin, and claudin-5 in senescent BMECs somewhat explained this dysfunction. Indeed, treatment of relatively old BMEC (passage 16) with a cocktail of senolytics (dasatinib and quercetin) or senomorphics targeting transcription factor NF-κB (QNZ), p38MAPK signaling pathway (BIRB-796) or pro-oxidant enzyme NADPH oxidase (VAS2870) until passage 20 rendered these cells more resistant to senescence and totally preserved BBB characteristics by restoring subcellular localization and expression of tight junction proteins. In conclusion, attempts that effectively mitigate accumulation of senescent endothelial cells in cerebrovasculature may prevent age-related BBB dysfunction and may be of prophylactic or therapeutic value to extend lifelong health and wellbeing.

Pathogeneses and Imaging Features of Cerebral White Matter Lesions of Vascular Origins.

White matter lesion (WML), also known as white matter hyperintensities or leukoaraiosis, was first termed in 1986 to describe the hyperintense signals on T2-weighted imaging (T2WI) and fluid-attenuated inversion recovery (FLAIR) maps. Over the past decades, a growing body of pathophysiological findings regarding WMLs have been discovered and discussed. Currently, the generally accepted WML pathogeneses mainly include hypoxia-ischemia, endothelial dysfunction, blood-brain barrier disruption, and infiltration of inflammatory mediators or cytokines. However, none of them can explain the whole dynamics of WML formation. Herein, we primarily focus on the pathogeneses and neuroimaging features of vascular WMLs. To achieve this goal, we searched papers with any type published in PubMed from 1950 to 2020 and cross-referenced the keywords including "leukoencephalopathy", "leukoaraiosis", "white matter hyperintensity", "white matter lesion", "pathogenesis", "pathology", "pathophysiology", and "neuroimaging". Moreover, references of the selected articles were browsed and searched for additional pertinent articles. We believe this work will supply the robust references for clinicians to further understand the different WML patterns of varying vascular etiologies and thus make customized treatment.

Nonthrombotic internal jugular venous stenosis may facilitate cerebral venous thrombosis.

AIMS: To explore the effect of nonthrombotic internal jugular venous stenosis (IJVS) exerted on cerebral venous thrombosis (CVT). METHODS: Patients with imaging confirmed CVT were enrolled into this real-world case-control study consecutively from January 2018 through April 2021, and were divided into CVT and IJVS-CVT groups, according to whether or not with non-thrombotic IJVS. Chi-square and logistic regression models were utilized for between-group comparison of thrombotic factors. RESULTS: A total of 199 eligible patients entered into final analysis, including 92 cases of CVT and 107 cases of IJVS-CVT. Chi-square revealed that thrombophilic conditions were found in majority of CVT, while only minority in the IJVS-CVT group (83.7% vs. 20.6%, p < 0.001). Multivariate logistic regression indicated that most identified thrombophilia were negatively related to IJVS-CVT (all p < 0.05), including oral contraceptive use (ß = -1.38), hyperhomocysteinemia (ß = -1.58), hematology (ß = -2.05), protein C/S deficiency (ß = -2.28), connective tissue disease (ß = -1.18) and infection (ß = -2.77). All recruited patients underwent standard anticoagulation, 10 cases in IJVS-CVT group also received jugular angioplasty for IJVS correction. Most participants obtained alleviations during 1-year follow-up. However, both clinical and imaging outcomes in IJVS-CVT group were not as good as those in CVT group (both p < 0.05). Moreover, 8 cases with CVT and 7 cases with IJVS-CVT were rehospitalized for CVT recurrences and underwent customized treatment. CONCLUSION: Nonthrombotic IJVS may be one of the risk factors of CVT. Anticoagulation might need to be suggested for IJVS patients.

Arterial spin labeling-MR may be an alternative to SPECT for evaluating cerebral perfusion in patients with unilateral middle cerebral artery stenosis.

OBJECTIVE: Cerebral blood flow (CBF) mapping of single-photon emission tomography (SPECT) is considered a gold standard for evaluating cerebral perfusion. However, invasiveness, high costs and strict technical requirements can limit its clinical use. We aimed to evaluate the concordance of CBF maps obtained from SPECT and pseudo-continuous arterial spin labeling magnetic resonance (PCASL-MR) imaging for evaluating cerebral perfusion. METHODS: PCASL-MR/SPECT-CBF maps were obtained from 16 eligible patients with unilateral middle cerebral artery stenosis (MCAS). Three slices (basal ganglia, semi-oval center and cerebellum) on both PCASL-MR and SPECT maps were divided into different regions of interest (ROIs) according to the ASPECT criterion, arterial territories, and cerebral hemispheres, respectively. The concordance of the two types of CBF maps and the specificity and sensitivity of PCASL-MR imaging on predicting regional hypoperfusion were calculated. RESULTS: A total of 448 ROIs were divided according to the ASPECT criterion, 192 ROIs partitioned in accordance with arterial territories, and 96 ROIs delineated based on cerebral hemispheres were analyzed. PCASL-MR imaging exhibited 83.78% to 100% sensitivity, 90.19% to 95.83% specificity for detection of hypoperfusion. Qualitative analyses revealed a strong concordance between PCASL-MR and SPECT on reflecting regional cerebral hypoperfusion (Kappa coefficient = 0.662-0.920, p < 0.01). Semi-quantitative analysis by ΔCBF revealed moderate consistency (Spearman correlation coefficient = 0.610-0.571). CONCLUSIONS: Our findings suggest that PCASL-MR may be a promising non-invasive, inexpensive alternative to SPECT for evaluating cerebral perfusion accurately in patients with symptomatic MCAS.

High-resolution combined arterial spin labeling MR for identifying cerebral arterial stenosis induced by moyamoya disease or atherosclerosis.

BACKGROUND: Distinguishing moyamoya disease (MMD) from intracranial atherosclerotic stenosis (IAS) is critical for its treatment and outcome evaluation. This study aimed to use the combined sequences of high-resolution magnetic resonance imaging (HRMRI) and arterial spin labeling MR (ASL-MR) to identify the two entities accurately. METHODS: This prospective study enrolled 58 patients with middle cerebral artery (MCA) steno-occlusion identified by digital subtraction angiography (DSA), including 27 cases of MMD and 31 cases of IAS. All patients underwent MRA, HRMRI and ASL-MR prior to DSA. Two radiologists blinded to DSA results analyzed the MR images. The inner and outer diameters of the target arteries, the wall thickness of the stenotic segment, and the perfusion status in the territories of the target arteries [cerebral blood flow (CBF), cerebral blood volume (CBV) and arterial transit time (ATT)] were measured quantitatively. The differences between MMD and IAS regarding the aspects of HRMRI and Pseudo-continuous ASLMR (PCASL-MR) maps were analyzed based on both visual characteristics and data information. RESULTS: Regarding the HRMRI images, MMD tended to have homogeneous and concentric vessel-wall thickening as well as collaterals adjacent to the stenotic vessels; while IAS showed eccentric and heterogeneous vessel-wall thickening. For the CBF maps of PCASL-MR, abnormal hyper-perfused spots embedded inside the hypo-perfused regions were observed in MMD instead of IAS. Quantitative analysis revealed that MMD displayed smaller inner and outer diameters, and smaller maximum wall thickness, higher average value of CBF, CBV and ATT, and higher maximum value of CBF and CBV, when compared to IAS (all P<0.01). The average wall thickness and the maximum value of ATT showed no significant difference between MMD and IAS (P>0.01). CONCLUSIONS: HRMRI combined with PCASL-MR may help distinguish MMD and IAS induced cerebral arterial stenosis and cerebral perfusion disorder accurately and non-invasively.

Probable risk factors of internal jugular vein stenosis in Chinese patients-A real-world cohort study.

OBJECTIVES: Extracranial venous anomalies, especially internal jugular vein stenosis (IJVS), have recently received increasing attention, however, its etiologies are uncertain. This study aimed to explore the probable risk factors of IJVS in Chinese PATIENTS AND METHODS: Eligible patients with IJVS confirmed by contrast-enhanced magnetic resonance venography (CE-MRV) were enrolled from October 2017 through October 2018. Probable risk factors were analyzed, including the conditions that may result in IJV wall damage, extraluminal compression, gender and age. RESULTS: A total of 133 patients enrolled in the final analysis, including 73 females and 60 males, the mean age were 54.83 ±â€¯15.25 years. In this IJVS cohort, the top two risks were previous hepatitis B virus (HBV) infection (48.9 %) and osseous compression (41.4 %). The IJVS cohort was divided into two subsets: extraluminal compression and non-compression. In the former, osseous compression (80.9 %) was the top risk factor, other risks including arterial (22.1 %) and lymph node compression (2.9 %). While, in the latter subset, the most common risk factor was previous HBV infection (46.2 %). In addition, cerebral venous sinus thrombosis (CVST) in non-compression subset was more common than that in extraluminal compression subset (21.5 % VS. 2.9 %, p = 0.001). When considered the gender (Male vs. Female), the ratios were 28.3 % vs. 0 % of smoking, p < 0.001, 16.67 % vs. 1.37 % of hyperhomocysteinemia, p = 0.002, and 11.67 % vs. 1.37 % of hyperuricemia, p = 0.023. In the subset with age less than 45 years, the top three risks included CVST (56.25 %), immunological diseases (55.56 %), and hyperhomocysteinemia (50.00 %), while, in the subset with the ages over 60 years, type-2 diabetes (66.66 %), carotid artery compression (53.33 %), previous HBV infection (52.31 %), and osseous compression (49.09 %) were more common than others. CONCLUSION: This study illustrates the probable risks of IJVS may be diverse, in which osseous compression and previous HBV infection may be the top two probable risks of IJVS in Chinese. This is the biggest difference from previous reports based on Caucasian.

Progress in moyamoya disease.

Moyamoya disease is characterized by progressive stenosis or occlusion of the intracranial portion of the internal carotid artery and their proximal branches, resulting in ischemic or hemorrhagic stroke with high rate of disability and even death. So far, available treatment strategies are quite limited, and novel intervention method is being explored. This review encapsulates current advances of moyamoya disease on the aspects of epidemiology, etiology, clinical features, imaging diagnosis and treatment. In addition, we also bring forward our conjecture, which needs to be testified by future research.

Cervical spondylotic internal jugular venous compression syndrome.

AIMS: This study aimed to identify the clinical profiles of cervical spondylosis-related internal jugular vein stenosis (IJVS) comprehensively. METHODS: A total of 46 patients, who were diagnosed as IJVS induced by cervical spondylotic compression were recruited. The clinical manifestations and imaging features of IJVS were presented particularly in this study. RESULTS: Vascular stenosis was present in 69 out of the 92 internal jugular veins, in which, 50.7% (35/69) of the stenotic vessels were compressed by the transverse process of C1, and 44.9% (31/69) by the transverse process of C1 combined with the styloid process. The transverse process of C1 compression was more common in unilateral IJVS (69.6% vs 41.3%, P = 0.027) while the transverse process of C1 combined with the styloid process compression had a higher propensity to occur in bilateral IJVS (52.2% vs 30.4%, P = 0.087). A representative case underwent the resection of the elongated left lateral mass of C1 and styloid process. His symptoms were ameliorated obviously at 6-month follow-up. CONCLUSIONS: This study proposes cervical spondylotic internal jugular venous compression syndrome as a brand-new cervical spondylotic subtype. A better understanding of this disease entity can be of great relevance to clinicians in making a proper diagnosis.

Risk factors and predictors of outcomes in 243 Chinese patients with cerebral venous sinus thrombosis: A retrospective analysis.

OBJECTIVES: To investigate the risk factors and predictors of outcomes in a cohort of Chinese patients with cerebral venous sinus thrombosis (CVST), so as to provide a reference for customized clinical decision. PATIENTS AND METHODS: A total of 243 Chinese patients, diagnosed as a first CVST were enrolled in this retrospective study from March 2013 through April 2017. Risk factors and predictors of outcomes for CVST were summarized and analyzed by Chi-square test and logistic regression analysis. RESULTS: Of the 243 cases, obstetric cause (19.8%) was the leading risk factor for CVST, followed by infection (17.7%) and anemia (17.7%). Gender differences in the risk factors for CVST were analyzed, showing that obstetric cause was the top risk factor in female, while hyperhomocysteinemia (22.3%) was the top risk factor in male. In age subgroups, obstetric cause (26.3%) and anemia (17.6%) were more commonly observed in age ≤ 44 years and age > 44 years subgroup, respectively. The ratio of poor outcomes (mRS = 3-6) in this cohort was 23.0%, and central nervous system (CNS) infection was closely related to poor outcomes at discharge (p = 0.023). CONCLUSION: The predominant risk factor for CVST, in this Chinese cohort, may still be obstetric cause in female and hyperhomocysteinemia in male. In addition, CNS infection may predict poor outcomes in CVST patients.

Normobaric oxygen: a novel approach for treating chronic cerebral circulation insufficiency.

Chronic cerebral circulation insufficiency (CCCI) is viewed as an alarming state induced by long-term reduction in cerebral perfusion, which is associated with neurological deficits and high risk of stroke occurrence or recurrence. CCCI accounts for a large proportion of both outpatients and inpatients with cerebrovascular diseases, while management of CCCI remains a formidable challenge to clinicians. Normobaric oxygen (NBO) is an adjuvant hyperoxygenation intervention supplied with one atmosphere pressure (1 ATA =101.325 kPa). A plethora of studies have demonstrated the efficacy of NBO on the penumbra in acute stroke. NBO has been shown to increase the oxygen pressure, raise the intracranial blood flow, protect blood-brain barrier and enhance neuroprotective effects. As similar underlying mechanisms are shared by the penumbra in stroke and the ischemic-hypoxic brain tissues in CCCI, we speculate that NBO may serve as a promising therapeutic strategy for attenuating short-term symptoms or improving long-term clinical outcomes among patients with CCCI. Due to the scant research exploring the efficacy and safety of NBO for treating CCCI so far, both experimental and clinical studies are warranted to verify our hypothesis in the future.

Efficacy of remote ischemic conditioning on improving WMHs and cognition in very elderly patients with intracranial atherosclerotic stenosis.

Our previous study revealed that remote ischemic conditioning (RIC) reduced the incidence of stroke or TIA in octo- and nonagenarians with intracranial atherosclerotic stenosis (ICAS). Herein, we aimed to investigate whether RIC would influence the progression of white matter hyperintensities (WMHs) and cognitive impairment in the same group of patients. Fifty-eight patients with ICAS were randomly assigned in a 1:1 ratio to receive standard medical treatment with RIC (n=30) versus sham-RIC (n=28). The RIC protocol consisted of 5 cycles of alternating 5-min ischemia and 5-min reperfusion applied in the bilateral upper arms twice daily for 300 days. The efficacy outcomes included WMHs change on T2 FLAIR sequences, estimated by the Fazekas scale and Scheltens scale, cognitive change as assessed by the MMSE and MoCA, and some clinical symptoms within 300-day follow-up. Compared with the baseline, RIC treatment significantly reduced Fazekas and Scheltens scores at both 180-day (both p<0.05) and 300-day (both p<0.01) follow-ups, whereas no such reduction was observed in the control group. In the RIC group, Fazekas scores were significantly lower at 300-day follow-up (p<0.001) while Scheltens scores were significantly lower at both 180-day and 300-day follow-ups (both p<0.001), as compared with the control group. There were statistically significant between-group differences in the overall MMSE or MoCA scores, favoring RIC at 180-day and 300-day follow-ups (all p<0.05). RIC may serve as a promising adjunctive to standard medical therapy for preventing the progression of WMHs and ameliorating cognitive impairment in very elderly patients with ICAS.

Batroxobin in combination with anticoagulation may promote venous sinus recanalization in cerebral venous thrombosis: A real-world experience.

AIMS: The objective of this study was to evaluate cerebral venous recanalization with magnetic resonance black-blood thrombus imaging (MRBTI) in patients with cerebral venous thrombosis (CVT) who underwent batroxobin treatment in combination with anticoagulation. METHODS: A total of 31 CVT patients were enrolled in this real-world registry study. The patients were divided into batroxobin (n = 21) and control groups (n = 10). In addition to the same standard anticoagulation as in the control group, patients in the batroxobin group underwent intravenous batroxobin for a total of three times. RESULTS: In the batroxobin group compared with the control group, we found better odds of recanalization degree [adjusted OR (95%CI) of 8.10 (1.61-40.7)] and segment-stenosis attenuation [adjusted OR (95%CI) of 4.48 (1.69-11.9)] with batroxobin treatment. We further noted a higher ratio of patients with the attenuation of stenosis [adjusted OR (95%CI) of 26.4 (1.10-635)]; as well as a higher ratio of segments with stenosis reversion [adjusted OR (95%CI) of 4.52 (1.48-13.8)]. However, neurological deficits between the two groups showed no statistical difference at 90-day follow-up (P > 0.05). CONCLUSIONS: Batroxobin may promote venous sinus recanalization and attenuate CVT-induced stenosis. Further randomized study of this promising drug may be warranted to better delineate the amount of benefit.

Clinical Characteristics and Neuroimaging Findings in Internal Jugular Venous Outflow Disturbance.

Recently, internal jugular vein stenosis (IJVS) is gaining increasing attention from clinical researchers due to a series of confounding symptoms that impair the quality of life in affected individuals but cannot be explained by other well-established causes. In this study, we aimed to elucidate the clinical features, neuroimaging characteristics and pathogenesis of IJVS, and explore their possible correlations, in attempt to provide useful clues for clinical diagnosis and treatment. Forty-three eligible patients with unilateral or bilateral IJVS confirmed by contrast-enhanced magnetic resonance venography of the brain and neck were enrolled in this study. Magnetic resonance imaging along with magnetic resonance angiography or computed tomography angiography was applied to identify the radiological pattern of parenchymal or arterial lesions. Cerebral perfusion and metabolism were evaluated by single-photon emission computed tomography (SPECT). Of the 43 patients (46.0 ± 16.0 years old; 30 female), 14 (32.6%) had bilateral and 29 had unilateral IJVS. The common clinical symptoms at admission were tinnitus (60.5%), tinnitus cerebri (67.6%), headache (48.8%), dizziness (32.6%), visual disorders (39.5%), hearing impairment (39.5%), neck discomfort (39.5%), sleep disturbance (60.5%), anxiety or depression (37.5%) and subjective memory decline (30.2%). The presence of bilateral demyelination changes with cloudy-like appearance in the periventricular area and/or centrum semiovale was found in 95.3% (41/43) patients. SPECT findings showed that 92.3% (24/26) patients displayed cerebral perfusion and metabolism mismatch, depicted by bilaterally and symmetrically reduced cerebral perfusion and increased cerebral glucose consumption. IJVS may contribute to alterations in cerebral blood flow and metabolism, as well as white matter lesion formation, all of which may account for its clinical manifestations.

Remote ischemic conditioning: a promising therapeutic intervention for multi-organ protection.

Despite decades of formidable exploration, multi-organ ischemia-reperfusion injury (IRI) encountered, particularly amongst elderly patients with clinical scenarios, such as age-related arteriosclerotic vascular disease, heart surgery and organ transplantation, is still an unsettled conundrum that besets clinicians. Remote ischemic conditioning (RIC), delivered via transient, repetitive noninvasive IR interventions to distant organs or tissues, is regarded as an innovative approach against IRI. Based on the available evidence, RIC holds the potential of affording protection to multiple organs or tissues, which include not only the heart and brain, but also others that are likely susceptible to IRI, such as the kidney, lung, liver and skin. Neuronal and humoral signaling pathways appear to play requisite roles in the mechanisms of RIC-related beneficial effects, and these pathways also display inseparable interactions with each other. So far, several hurdles lying ahead of clinical translation that remain to be settled, such as establishment of biomarkers, modification of RIC regimen, and deep understanding of underlying minutiae through which RIC exerts its powerful function. As this approach has garnered an increasing interest, herein, we aim to encapsulate an overview of the basic concept and postulated protective mechanisms of RIC, highlight the main findings from proof-of-concept clinical studies in various clinical scenarios, and also to discuss potential obstacles that remain to be conquered. More well designed and comprehensive experimental work or clinical trials are warranted in future research to confirm whether RIC could be utilized as a non-invasive, inexpensive and efficient adjunct therapeutic intervention method for multi-organ protection.

To Predict Visual Deterioration According to the Degree of Intracranial Hypertension in Patients with Cerebral Venous Sinus Thrombosis.

BACKGROUND: Visual damage is one of the most common complications of cerebral venous sinus thrombosis (CVST)-associated intracranial hypertension (IH). This study is aimed at stratifying the risk of IH-induced visual damage in an attempt to predict its deterioration and prevent high-risk patients from irreversible eyesight impairment promptly. METHODS: A total of 94 patients with confirmed diagnosis of CVST were eligible for enrollment in this study. According to cerebrospinal fluid pressure at admission, the involved patients were classified into mild IH (< 250 mmH2O), moderate IH (250-330 mmH2O), and severe IH (≥330 mmH2O) groups. RESULTS: The ratio of visual deterioration in the severe IH group was 75%, which was significantly higher than in either the moderate (44.4%) or the mild groups (14.3%). As regards subjects without visual symptoms at admission, visual deterioration occurred in 9.4 ± 4.5 days after admission in the severe group while it occurred in 30.5 ± 16.8 days in the moderate group (p = 0.024). The conditional inference tree and random forest revealed that severe IH might be considered as an index of visual deterioration. Visual field defect, fading eyesight, and papilledema were significantly worse in patients with severe IH as compared to patients with mild or moderate IH, all p < 0.01. CONCLUSIONS: IH ≥330 mmH2O may be a cut-off value to predict the deterioration of visual damage in CVST, revealing that ophthalmologic interventions should be considered in a timely manner in this condition, particularly when recanalization of cerebral venous sinus cannot be achieved within a short time.