Revisiting the predictive role of truncal-type occlusion sign for acute large vessel stroke treated by endovascular thrombectomy: A scoping review.

Background and purpose The truncal type occlusion (TTO) sign observed during endovascular thrombectomy (EVT) is thought to predict the etiology and prognosis of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, the interpretation of the present results and the clinical utility of this sign needs further investigation. This scoping meta-review aimed to assess the predictive value of the TTO sign, thus identifying methodological limitations in current study designs. Methods Studies published up to January 2023 were identified by systematically searching PubMed, Embase, and Web of Science. A meta-analysis was performed to quantitatively synthesize the evidence on the predictive value of the TTO sign. An 8-point scale was introduced to narratively summarize the current evidence level and methodological quality of included studies. Results We included 10 studies in this review. For the prediction of intracranial atherosclerotic stenosis, the sensitivity, specificity, PLR and NLR of the TTO sign were 0.73, 0.87, 5.5 and 0.31, respectively (all p<0.05). For recanalization failure after primary thrombectomy, the sensitivity, specificity, PLR and NLR were 0.44, 0.91, 4.9 and 0.61, respectively (all p<0.05). The strength of evidence was low due to the methodological limitations and lack of adjustment for potential confounders. Conclusion The predictive values of the TTO sign for the etiology of LVO-AIS was considerable but seemed limited for current interpretation. Several confounders could influence the determination and predictive value of the TTO sign, requiring methodological adjustments in future research. Endovascular practitioners encountering this sign during thrombectomy should draw specific attention to stroke etiology, thus promoting timely adjustment of intra- and postprocedural strategies.

Prognostic value of the neutrophil-to-lymphocyte ratio in acute ischemic stroke patients treated with intravenous thrombolysis: a systematic review and meta-analysis.

BACKGROUND: The relationship between the neutrophil-to-lymphocyte ratio (NLR) and poor prognostics in acute ischemic stroke (AIS) patients who receive intravenous thrombolysis (IVT) remains controversial. The purpose of this systematic review and meta-analysis was to evaluate the association between the NLR and poor prognosis after IVT. Furthermore, we aimed to determine whether the NLR at admission or post-IVT plays a role in AIS patients who received IVT. METHODS: The PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases were searched for relevant articles until October 7, 2020. Cohort and case-control studies were included if they were related to the NLR in AIS patients treated with IVT. Odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were pooled to estimate the relationship between NLR and poor prognosis after IVT. A random effects model was used to calculate the pooled data. RESULTS: Twelve studies, including 3641 patients, met the predefined inclusion criteria. Higher NLRs were associated with an increased risk of hemorrhagic transformation (HT) (OR = 1.33, 95 % CI = 1.14-1.56, P < 0.001) and a poor 3-month functional outcome (OR = 1.64, 95 % CI = 1.38-1.94, P < 0.001) in AIS patients who received IVT. Subgroup analysis suggested that the NLR at admission rather than post-IVT was associated with a higher risk of HT (OR = 1.33, 95 % CI = 1.01-1.75, P = 0.039). There was no statistically significant difference between higher NLRs and 3-month mortality (OR = 1.14, 95 % CI = 0.97-1.35, P = 0.120). CONCLUSIONS: A high NLR can predict HT and poor 3-month functional outcomes in AIS patients who receive IVT. The NLR at admission rather than the post-IVT NLR was an independent risk factor for an increased risk of HT after IVT.

Comparison of the Diagnostic Performances of Ultrasound, High-Resolution Magnetic Resonance Imaging, and Positron Emission Tomography/Computed Tomography in a Rabbit Carotid Vulnerable Plaque Atherosclerosis Model.

OBJECTIVES: Our study aimed to evaluate the diagnostic performances of 3 routine examination methods for cerebrovascular disease in a rabbit carotid artery atherosclerosis model. METHODS: A total of 12 New Zealand rabbits were included: 4 in a control group and 8 in an experimental group. A clinically relevant atherosclerosis rabbit model was induced by left common carotid artery ligation and a 12-week high-fat diet. Atherosclerosis was further confirmed by a histopathologic analysis. Then carotid ultrasound (US) imaging, high-resolution magnetic resonance imaging (HRMRI), and positron emission tomography (PET)/computed tomography (CT) were performed on this model to evaluate the diagnostic performances. RESULTS: Carotid US showed plaque formation in the left common carotid artery and little plaque in the right common carotid artery in the experimental group. In addition, HRMRI showed stenosis formation in the left common carotid artery in the experimental group. At the horizontal level, plaques were found in the left common carotid artery, and no plaques were found in the right common carotid artery in the experimental group. Also, PET/CT showed local hypermetabolism and vulnerable plaques in the left common carotid artery of the experimental group, whereas no hypermetabolism was found in the right common carotid artery of the experimental group. Moreover, the soft plaques detected by carotid US were different from the vulnerable plaques detected by PET/CT. The unstable plaques on HRMRI were the same as the hypermetabolic vulnerable plaques on PET/CT. CONCLUSIONS: High-resolution MRI is recommended for the evaluation of neck and intracranial vascular stenosis and plaque properties in patients with stroke.

Knockdown of microRNA-17-5p Enhances the Neuroprotective Effect of Act A/Smads Signal Loop After Ischemic Injury.

Cerebral ischemic injury is a leading cause of human mortality and disability, seriously threatening human health in the world. Activin A (Act A), as a well-known neuroprotective factor, could alleviate ischemic brain injury mainly through Act A/Smads signaling. In our previous study, a noncanonical Act A/Smads signal loop with self-amplifying property was found, which strengthened the neuroprotective effect of Act A. However, this neuroprotective effect was limited due to the self-limiting behavior mediated by Smad anchor for receptor activation (SARA) protein. It was reported that microRNA-17-5p (miR-17-5p) could suppress the expression of SARA in esophageal squamous cell carcinoma. Thus we proposed that knockdown of miR-17-5p could strengthen the neuroprotective effect of Act A/Smads signal loop through SARA. To testify this hypothesis, oxygen-glucose deficiency (OGD) was introduced to highly differentiated rattus pheochromocytoma (PC12) cells. After the transfection of miR-17-5p mimic or inhibitor, the activity of Act A signal loop was quantified by the expression of phosphorylated Smad3. The results showed that suppression of miR-17-5p up-regulated the expression of SARA protein, which prolonged and strengthened the activity of Act A signaling through increased phosphorylation of downstream Smad3 and accumulation of Act A ligand. Further luciferase assay confirmed that SARA was a direct target gene of miR-17-5p. These practical discoveries will bring new insight on the endogenous neuroprotective effects of Act A signal loop by interfering a novel target: miR-17-5p.

Activin A/Smads signaling pathway negatively regulates Oxygen Glucose Deprivation-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.

Activin A (Act A), a member of the transforming growth factor-beta (TGF-ß), reduces neuronal apoptosis during cerebral ischemia through Act A/Smads signaling pathway. However, little is known about the effect of Act A/Smads pathway on autophagy in neurons. Here, we found that oxygen-glucose deprivation (OGD)-induced autophagy was suppressed by exogenous Act A in a concentration-dependent manner and enhanced by Act A/Smads pathway inhibitor (ActRIIA-Ab) in neuronal PC12 cells. These results indicate that Act A/Smads pathway negatively regulates autophagy in OGD-treated PC12 cells. In addition, we found that c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase pathways are involved in the OGD-induced autophagy. The activation of JNK and p38 MAPK pathways in OGD-treated PC12 cells was suppressed by exogenous Act A and enhanced by ActRIIA-Ab. Together, our results suggest that Act A/Smads signaling pathway negatively regulates OGD-induced autophagy via suppression of JNK and p38 MAPK pathways in neuronal PC12 cells.

Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop.

Activin A (Act A), a member of transforming growth factor-ß superfamily, plays a neuroprotective role in multiple neurological diseases through Act A/Smads signal activation. Traditionally, the up-regulation of Act A gene and extracellular Act A accumulation show the signal activation as a linear pathway. However, one of our discoveries indicated that Act A could lead a loop signaling in ischemic injury. To clarify the characteristic of this loop signaling in a non-pathological state, we up-regulated the expression of Act A, monitored extracellular Act A accumulation and examined the activity of Act A signaling, which was quantified by the expression of phosphorylated Smad3 and the fluorescence intensity of Smad4 in nuclei. The results demonstrated a noncanonical Act A signal loop with self-amplifying property in PC12 cells. Further, it showed self-limiting behavior due to temporary activation and spontaneous attenuation. This periodic behavior of Act A signal loop was found to be regulated by the level of Smad anchor for receptor activation (SARA). Moreover, increased activity of Act A signal loop could promote PC12 cell proliferation and enhance the survival rate of cells to Oxygen-Glucose Deprivation. These practical discoveries will bring new insight on the functional outcome of Act A signaling in neurological diseases by the further understanding: loop signaling.

The ABCD2 score may underestimate the short-term risk of stroke in Chinese population: A meta-analysis.

OBJECTIVES: The ABCD2 score has been commonly used to triage patients with transient ischemic attack (TIA) who are at high risk for imminent stroke. However, its accuracy in predicting short-term stroke risk among TIA patients in China remains unclear. METHODS: All eligible studies published up to May 2014 were identified by searching Medline, PubMed, Embase, the China Knowledge Resource Integrated Database (CNKI) and the China Biological Medicine Database (CBM-disc), as well as unpublished articles manually scanned. The strength of the associations between treatments and outcomes was estimated by incorporated risk ratios (RRs) and 95% confidence intervals (CIs) using the Mantel-Haenszel statistical method. RESULTS: Eight and 32 studies, which validated the value for predicting the risk of stroke 2 and 7 days after TIA respectively, were included. We calculated the RRs and CIs for 2- and 7-day prediction for stroke (low: RR=0.43, 95% CI=0.17-1.10, I2=0%; moderate: RR=0.42, 95% CI=0.26-0.67, I2=0%; high: RR=0.32, 95% CI=0.21-0.48, I2=0%; and low: RR=0.29, 95% CI=0.20-0.44, I2=0%; moderate: RR=0.27, 95% CI=0.23-0.33, I2=0%; high: RR=0.22, 95% CI=0.18-0.27, I2=1%). CONCLUSIONS: This meta-analysis indicated that the ABCD2 score may highly under-predict the short-term occurrence of stroke after TIA for the Chinese population compared with the original model derived from Caucasian populations, which may lead to neglect of the short-term risk for stroke in the clinical practice.

Angiographic Pattern of M1 Stenosis Predicts Territorial Stroke in Patients Receiving Aggressive Medication without Stenting.

OBJECTIVE: To evaluate the relationship between different angiographic patterns of middle cerebral artery M1 segment stenosis and related territorial stroke in patients receiving aggressive medical treatment without stenting. METHODS: We retrospectively reviewed our patient registry database to identify ICAS patients diagnosed by digital subtraction angiography between January 2017 and December 2020 and identified 3 different angiographic patterns (normal, shift, and dilation) in 124 patients with M1 stenosis. The association between these patterns and recurrent ischemic stroke in the M1 territory was analyzed. RESULTS: The rates of recurrent M1 territorial stroke and transient ischemic attack in the normal group, shift group, dilation group and shift-dilation group were 34.5%, 35.0%, 78.3%, and 44.4% respectively. In patients with the shift pattern, the rate of recurrent stroke is significantly higher at a deflection angle ≥9.32° than at a deflection angle <9.32°(P < 0.05). In patients with dilation pattern, the rate of recurrent stroke is significantly higher than patients with non-dilation pattern (72.3% vs. 36.8%, P < 0.05). CONCLUSIONS: Angiographic patterns of M1 stenosis may predict recurrent territorial strokes, thus providing a surrogate marker to identify high-risk patients for potential endovascular treatment.

Revisiting the role of TEG-PM in stroke prevention by drug selection for mono-antiplatelet medication following dual-antiplatelet treatment.

BACKGROUNDS: Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel for minor strokes or TIAs has been demonstrated in several RCTs. Whether drug selection for mono-antiplatelet therapy (MAPT) following DAPT may influence stroke recurrence has not been clarified, especially for patients with intracranial atherosclerosis stenosis (ICAS). The Thrombelastography Platelet Mapping (TEG-PM) assay claimed to be capable of monitoring platelet function secondary to antiplatelet therapy. PURPOSE: The aim of this study was to investigate the preventive role of TEG-PM in individualized drug selection for MAPT following DAPT in patients with minor stroke or TIA. METHODS: We retrospectively reviewed our patient database to identify individuals with minor stroke or TIA between February 2019 and July 2022. Patients were divided into ICAS and non-ICAS groups, and the efficacy and safety of TEG-PM-guided MAPT for stroke prevention after minor stroke or TIA were investigated in each group. RESULTS: ICAS patients with TEG-PM-guided MAPT had lower rates of recurrent stroke than patients without TEG-PM guidance during a mean follow-up period of 18.1 months (6.3% vs 15.2%; p = 0.04). Patients without ICAS also tended to benefit from TEG-PM-guided MAPT with lower rates of stroke recurrence (2.6% vs 8.7%; p = 0.02). No difference in the safety outcome of any bleeding events was observed in patients with TEG-PM-guided MAPT and those without (ICAS group, 2.1% vs 3.0%; p = 0.68; non-ICAS group, 1.3% vs 2.3%; p = 0.79). CONCLUSION: The TEG-PM could be a tangible preprocessing in drug selection for MAPT following DAPT in patients with minor strokes or TIAs, especially for those with non-stented ICASs.

Effects of SARA on oxygen-glucose deprivation in PC12 cell line.

Ischemic stroke is a major composition of cerebrovascular disease, seriously threatening to human health in the world. Activin A (ActA), belonging to transforming growth factor-beta (TGF-ß) super family, plays an important role in the hypoxic-ischemic brain injury through ActA/Smads pathway. While as an essential phosphorylation assistor in TGF-ß signaling, the functions and mechanisms of smad anchor for receptor activation (SARA) in ischemic brain injury remain poorly understood. To solve this problem and explore the pathological processes of ischemic stroke, we used an Oxygen-Glucose deprivation (OGD) model in nerve growth factor-induced differentiated rattus PC12 pheochromocytoma cells and down regulated the expressions of SARA by RNA interference technology. Our results showed that the repression of SARA before OGD exposure reduced the expressions of Smad2, 3, 4 mRNA and the phosphorylation rate of Smad2 protein, but it did not affect the mRNA expressions of Smad7. After OGD treatment, ActA/Smads pathway was activated and the expression of SARA in the SARA pre-repression group was significantly up-regulated. The pre-repression of SARA increased the sensitivities of nerve-like cells to OGD damage. Moreover, the mRNA expression of Smad7 which was supposed to participate in the negative feedback of ActA/Smads pathway was also elevated due to OGD injury. Taken together, these results suggest a positive role of SARA in assisting the phosphorylation of Smad2 and maintaining the neuron protective effect of ActA/Smads pathway.

Endogenous protection derived from activin A/Smads transduction loop stimulated via ischemic injury in PC12 cells.

Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.

Favoring the cognitive-motor process in the closed-loop of BCI mediated post stroke motor function recovery: challenges and approaches.

The brain-computer interface (BCI)-mediated rehabilitation is emerging as a solution to restore motor skills in paretic patients after stroke. In the human brain, cortical motor neurons not only fire when actions are carried out but are also activated in a wired manner through many cognitive processes related to movement such as imagining, perceiving, and observing the actions. Moreover, the recruitment of motor cortexes can usually be regulated by environmental conditions, forming a closed-loop through neurofeedback. However, this cognitive-motor control loop is often interrupted by the impairment of stroke. The requirement to bridge the stroke-induced gap in the motor control loop is promoting the evolution of the BCI-based motor rehabilitation system and, notably posing many challenges regarding the disease-specific process of post stroke motor function recovery. This review aimed to map the current literature surrounding the new progress in BCI-mediated post stroke motor function recovery involved with cognitive aspect, particularly in how it refired and rewired the neural circuit of motor control through motor learning along with the BCI-centric closed-loop.

Drawing time-density curve with Fiji/ImageJ: An alternative approach for parametric coding of cerebral digital subtraction angiography.

BACKGROUND: Quantitative spatiotemporal analysis of digital subtraction angiography could support clinical decision making for the management of cerebral vascular disease. However, there is a lack of free and user-friendly applications. The objective of our study is to devise a free and simple solution for parametric coding of digital subtraction angiography. NEW METHOD: By driving the time-density curves in the region of interest, the digital subtraction angiography images were color-coded and quantitatively analyzed using fully open-source and free software (Fiji/ImageJ). The similarity factor (f2) was used to compare the resolution profiles between time-density curves generated with commercial software on the Siemens workstation (syngo iFlow, Siemens Healthcare, Berlin, Germany) and our method. RESULTS AND COMPARISON WITH EXISTING METHOD: Sixteen patients diagnosed with acute ischemic stroke resulting from acute occlusion of the distal internal carotid artery or the first segment of the middle cerebral artery were selected for analysis. Angiography images were successfully processed with syngo iFlow and Fiji/ImageJ. The images processed with Fiji/ImageJ provided excellent anatomic and hemodynamic details. In all patients, the similarity factor (f2) values of the time-density curves derived from the same region of interest were 99.90 (range 99.85-99.95). CONCLUSIONS: The ImageJ/Fiji software provides a user-friendly and free alternative for parametric coding of digital subtraction angiography.

Optional or optimal? off-label stenting for intracranial atherosclerotic stenosis: A scoping review.

BACKGROUND: Intracranial atherosclerotic stenosis is a major cause of ischemic stroke. In addition to the Wingspan stent system, several self-expanding stents have been used off-label to treat intracranial atherosclerotic stenosis lesions. The purpose of this review is to assess the existing data on the off-label use of self-expanding stents in intracranial atherosclerotic stenosis, to highlight methodological limitations in current study designs, and thus providing strategies and precautions for clinical practice. METHODS: The PubMed, EMBASE, and the Cochrane Library databases were systematically searched for relevant articles published up to April 2022. In addition to the meta analysis of Enterprise, Neuroform EZ and closed cell stent respectively, we used a narrative synthesis to summarize and discuss the appropriate strategies and precautions for the use of each stent. RESULTS: We identified 17 studies (1091 patients with 1124 lesions) reporting 6 types of off-label self-expanding stents. The most common endpoints reported were incidence of short-term complications (range: 0-15.8%, median: 3.8%), long-term complications (range: 0-12.0%, median: 0%). Potential risks include infeasibility of stenting hard lesions or tortuous vessels, stent migration, and in-stent thrombosis. Less is known about the conditions that are appropriate for an optimal stent (e.g., open-cell, close-cell, hybrid cell). There was considerable heterogeneity across studies with regards to study populations and study designs. CONCLUSIONS: The potential risks and benefits should be carefully considered when using off-label stents for intracranial atherosclerotic stenosis, particularly given the current evidence power. As a potential option for the Wingspan stent, based on device's approval only, a tailored approach with lesion-specific devices could be beneficial in certain patients.

Staged angioplasty: A sensible approach to prevent hyperperfusion syndrome after carotid artery stenting? A meta-analysis.

OBJECTIVE: To investigate whether staged angioplasty (SAP) is a safe and effective treatment to prevent hyperperfusion syndrome after carotid artery stenting (CAS). METHODS: A systematic literature search was performed according to established criteria to identify eligible articles published before October 2020. Pooled dichotomous data were presented as odds ratios (OR) and corresponding 95% confidence intervals (CI) using random-effect models. The efficacy endpoints were hyperperfusion syndrome (HPS), hyperperfusion phenomenon (HPP), and intracerebral hemorrhage (ICH). The safety endpoint was post-procedural thromboembolic events. The feasibility of the procedure was assessed by device-related adverse events (vessel dissection and failed angioplasty) in SAP. RESULTS: Ten studies (1030 participants) were eligible. SAP was superior to regular CAS in preventing HPS (OR = 0.35, 95% CI 0.14-0.86, P = 0.02). There was no significant difference in the rate of thromboembolic events between the SAP group and the regular CAS group. The rates of vessel dissection and failed angioplasty with the use of a 3.0-mm-diameter balloon were 5.4% and 0.4%, respectively. CONCLUSION: SAP may reduce the incidence of post-CAS HPS without increasing procedure-related complications. A 3.0-mm-diameter balloon used in SAP may be appropriate for Asian populations. However, the confounded study design and confused definitions of reporting items hinder the current recommendation of SAP in clinical use.

Does radiological conjugate eye deviation sign play a role in acute stroke imaging? A meta-analysis.

BACKGROUND AND PURPOSE: The diagnostic value of non-contrast CT (NCCT) in acute stroke imaging remains indispensable, especially under emergency conditions with limited resources. The radiological conjugate eye deviation (RCED) has been demonstrated as a NCCT sign to predict acute ischemic stroke (AIS) or AIS secondary to large vessel occlusion (LVO) in recent studies. We performed a meta-analysis to gain a better understanding into the predictive role of RCED for AISs and LVO-AISs. METHODS: We conducted a systematic literature search using PubMed, Embase, and Cochrane. The search focused on studies published between January 2000 and August 2020 that reported the predictive value of RCED for the diagnosis of AIS or LVO-AIS. Principal measurements of the meta-analysis were the overall sensitivity, specificity, the positive likelihood ratio (PLR), and the negative likelihood ratio (NLR) of RCED in predicting AIS and LVO-AIS. RESULTS: We included 11 studies (n = 2304). For AIS, RCED had a sensitivity of 0.37 (95% CI 0.27-0.47), a specificity of 0.86 (95% CI 0.73-0.93), the area under the receiver operating characteristic curve (AUC) was 0.58 (95% CI 0.53-0.62), PLR was 2.5 (95% CI 1.5-4.4), and NLR was 0.74 (95% CI 0.65-0.84). For LVO-AIS, RCED had a sensitivity of 0.63 (95% CI 0.46-0.77), a specificity of 0.77 (95% CI 0.71-0.82), AUC was 0.63 (95% CI 0.46-0.77), PLR was 2.7 (95% CI 1.7-4.3), and NLR was 0.49 (95% CI 0.3-0.78). CONCLUSION: RCED can be used to predict LVO-AIS. It is expected that this method will be extensively used and validated in acute stroke imaging, especially under emergency conditions with limited resources.

Better late than never: initial experience of intra-arterial pulsed-urokinase-injection as a salvage therapy for refractory sudden sensorineural hearing loss.

BACKGROUND AND PURPOSE: Cochlear vascular micro-thrombosis has been hypothesized as one of the pathogenic mechanisms for sudden sensorineural hearing loss (SSNHL) refractory to regular management. This study aimed to evaluate the feasibility and safety of intra-arterial pulsed-injection urokinase (IAPU) as a salvage therapy for SSNHL after the failure of conventional therapy. METHODS: We retrospectively reviewed our patient database to identify refractory SSNHL patients between November 2017 and July 2020. Study outcomes before and after the IAPU therapy were compared between IAPU and conventional therapy groups. RESULTS: Sixty-seven moderate-profound SSNHL patients (29 in IAUP group, 38 in control group) were included in this study. Compared to the control group, patients in the IAPU group showed more significant improvement in pure tone average (PTA) (34.2 ± 23.5 vs. 10.7 ± 13.1, p < 0.001) and degree of hearing recovery (total: 20.7% vs. 5.3%, partial: 24.1% vs. 10.5%, mild: 27.6% vs. 13.2% and non: 27.6% vs. 71.1%) 2 weeks after admission. In the IAPU group, a significant improvement of PTA (86.6 ± 11.5 vs. 54.6 ± 20.1 dB, p < 0.005) was observed on the first day after IAPU treatment. CONCLUSION: In carefully selected SSNHL cases with a highly suspected vascular origin, IAPU is a safe and effective therapy when conventional treatments have failed. Despite the encouraging findings of our work, large studies are needed to better investigate the strengths and limitations of this salvage therapy.

Neuroprotective effects of exogenous activin A on oxygen-glucose deprivation in PC12 cells.

Ischemic cerebrovascular disease is one of the most common causes of death in the World. Exogenous activin A (ActA) protects neurons against toxicity and plays a central role in regulating the brain's response to injury. In the present study, we investigated the mechanisms involved in the neuroprotective effects of ActA in a model of hypoxic-ischemic brain disease. We found that ActA could effectively increase the survival rate of PC12 cells and relieve oxygen-glucose deprivation (OGD) damage. To clarify the neuroprotective mechanisms of ActA, the effects of ActA on the ActA/Smad pathway and on the up-regulation of inducible nitric oxide synthase (NOS) and superoxide dismutase (SOD) were investigated using OGD in PC12 cells. The results showed that ActA could increase the expression of activin receptor IIA (ActRIIA), Smad3 and Smad4 and that 50 ng/mL and 100 ng/mL of ActA could reduce NO levels and increase SOD activity by 78.9% and 79.9%, respectively. These results suggested that the neuroprotective effects of ActA in ischemia could be related to the activation of the ActA/Smad signaling pathway and to its anti-oxidant activities.

Exploration of the mechanism of luteolin against ischemic stroke based on network pharmacology, molecular docking and experimental verification.

Stroke is a leading cause of morbidity and mortality worldwide. As the most common type of stroke cases, treatment effectiveness is still limited despite intensive research. Recently, traditional Chinese medicine has attracted attention because of potential benefits for stroke treatment. Among these, luteolin, a natural plant flavonoid compound, offers neuroprotection following against ischemic stroke, although the specific mechanisms are unknown. Here we used network pharmacology, molecular docking, and experimental verification to explore the mechanisms whereby luteolin can benefit stroke recovery. The pharmacological and molecular properties of luteolin were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The potential targets of luteolin and ischemic stroke were collected from interrogating public databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed by Funrich and Database for Annotation, Visualization and Integrated Discovery respectively, a luteolin-target-pathway network constructed using Cytoscape, Autodock vina was used for molecular docking simulation with Discovery Studio was used to visualize and analyze the docked conformations. Lastly, we employed an in vitro model of stroke injury to evaluate the effects of luteolin on cell survival and expression of the putative targets. From 95 candidate luteolin target genes, our analysis identified six core targets . KEGG analysis of the candidate targets identified that luteolin provides therapeutic effects on stroke through TNF signaling and other pathways. Our experimental analyses confirmed the conclusions analyzed above. In summary, the molecular and pharmacological mechanisms of luteolin against stroke are indicated in our study from a systematic perspective.

CT-negative Subarachnoid Hemorrhage Caused by Telangiectasia: A Case Report.

INTRODUCTION: At present, the mechanism of telangiectasia is unknown, but some evidence suggests that it may be related to genetic abnormalities. Telangiectasia may lead to bleeding of multiple sites. CT-negative subarachnoid hemorrhage is rare, which is mostly related to hemorrhage with a little amount of bleeding. CT-negative subarachnoid hemorrhage due to telangiectasia has not been reported. CASE REPORT: In this case report, the patient experienced severe headache with nausea, vomiting, and blurred vision for 12 days, and had a history of hypertension. Physical examination revealed a clear state of mind, normal speech, normal limb muscle strength, 2 transverse fingers of neck stiffness, and negative bilateral Babinski signs. Brain CT, MRI, MRA, and MRV showed no obvious abnormalities. SWI suggested the possibility of capillary dilation. The cerebrospinal fluid was pale yellow in appearance after lumbar puncture. DIAGNOSIS: The patient was diagnosed with subarachnoid hemorrhage (SAH) and capillary dilatation. INTERVENTIONS: Therapeutic management of blood pressure and brain edema was started. CONCLUSION: Lumbar puncture should be performed when subarachnoid hemorrhage is clinically suspected and CT is negative. While searching for the cause of subarachnoid hemorrhage, the presence of telangiectasia should be ascertained.