Light-Inducible Activation of TrkA for Probing Chronic Pain in Mice.

Chronic pain is a prevalent problem that plagues modern society, and better understanding its mechanisms is critical for developing effective therapeutics. Nerve growth factor (NGF) and its primary receptor, Tropomyosin receptor kinase A (TrkA), are known to be potent mediators of chronic pain, but there is a lack of established methods for precisely perturbing the NGF/TrkA signaling pathway in the study of pain and nociception. Optobiological tools that leverage light-induced protein-protein interactions allow for precise spatial and temporal control of receptor signaling. Previously, our lab reported a blue light-activated version of TrkA generated using light-induced dimerization of the intracellular TrkA domain, opto-iTrkA. In this work, we show that opto-iTrkA activation is able to activate endogenous ERK and Akt signaling pathways and causes the retrograde transduction of phospho-ERK signals in dorsal root ganglion (DRG) neurons. Opto-iTrkA activation also sensitizes the transient receptor potential vanilloid 1 (TRPV1) channel in cellular models, further corroborating the physiological relevance of the optobiological stimulus. Finally, we show that opto-iTrkA enables light-inducible potentiation of mechanical sensitization in mice. Light illumination enables nontraumatic and reversible (<2 days) sensitization of mechanical pain in mice transduced with opto-iTrkA, which provides a platform for dissecting TrkA pathways for nociception in vitro and in vivo.

Endoplasmic reticulum exit sites are segregated for secretion based on cargo size.

TANGO1, TANGO1-Short, and cTAGE5 form stable complexes at the endoplasmic reticulum exit sites (ERES) to preferably export bulky cargoes. Their C-terminal proline-rich domain (PRD) binds Sec23A and affects COPII assembly. The PRD in TANGO1-Short was replaced with light-responsive domains to control its binding to Sec23A in U2OS cells (human osteosarcoma). TANGO1-ShortΔPRD was dispersed in the ER membrane but relocated rapidly, reversibly, to pre-existing ERES by binding to Sec23A upon light activation. Prolonged binding between the two, concentrated ERES in the juxtanuclear region, blocked cargo export and relocated ERGIC53 into the ER, minimally impacting the Golgi complex organization. Bulky collagen VII and endogenous collagen I were collected at less than 47% of the stalled ERES, whereas small cargo molecules were retained uniformly at almost all the ERES. We suggest that ERES are segregated to handle cargoes based on their size, permitting cells to traffic them simultaneously for optimal secretion.

A novel nomogram to predict futile recanalization in patients with acute ischemic stroke undergoing mechanical thrombectomy.

Background and objective: Futile recanalization (FR) is defined as patients with acute ischemic stroke (AIS) due to large vessel occlusion who still exhibits functional dependence although undergoing successful mechanical thrombectomy (MT). We aimed to develop and validate a simple nomogram for predicting the probability of FR after MT treatment in AIS patients. Methods: Clinical data of AIS patients in the Jrecan clinical trial in China from March 2018 to June 2019 were collected as the derivation set (n = 162). Meanwhile, clinical data of AIS patients who underwent MT in Baotou Central Hospital and Ningbo No.2 Hospital from 2019 to 2021 were collected as the validation set (n = 170). Multivariate logistic regression analysis was performed for all variables that had p < 0.2 in the univariate analysis in the derivation set. The independent risk factors of FR were further screened out and a nomogram was constructed. The performance of the nomogram was analyzed in the derivation and validation set using C-index, calibration plots, and decision curves. Results: No significant difference in FR rate was detected between the derivation set and the validation set [88/162 (54.32%) and 82/170 (48.23%), p = 0.267]. Multivariate logistic regression analysis showed that age ≥ 65 years old (OR = 2.096, 95%CI 1.024-4.289, p = 0.043), systolic blood pressure (SBP) ≥ 180 mmHg (OR = 5.624, 95%CI 1.141-27.717, p = 0.034), onset to recanalization time (OTR) ≥ 453 min (OR = 2.759, 95%CI 1.323-5.754, p = 0.007), 24 h intracerebral hemorrhage (ICH; OR = 4.029, 95%CI 1.844 ~ 8.803, p < 0.001) were independent risk factors for FR. The C-index of the nomogram of the derivation set and the verification set were 0.739 (95%CI 0.662~0.816) and 0.703 (95%CI 0.621~0.785), respectively. Conclusion: The nomogram composed of age, SBP, OTR, and 24 h ICH can effectively predict the probability of FR after MT in AIS patients.

Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling.

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 􀁐g/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 􀁐g/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

Application of a nomogram model for the prediction of 90-day poor outcomes following mechanical thrombectomy in patients with acute anterior circulation large-vessel occlusion.

Background: The past decade has witnessed advancements in mechanical thrombectomy (MT) for acute large-vessel occlusions (LVOs). However, only approximately half of the patients with LVO undergoing MT show the best/independent 90-day favorable outcome. This study aimed to develop a nomogram for predicting 90-day poor outcomes in patients with LVO treated with MT. Methods: A total of 187 patients who received MT were retrospectively analyzed. Factors associated with 90-day poor outcomes (defined as mRS of 4-6) were determined by univariate and multivariate logistic regression analyzes. One best-fit nomogram was established to predict the risk of a 90-day poor outcome, and a concordance index was utilized to evaluate the performance of the model. Additionally, 145 patients from a single stroke center were retrospectively recruited as the validation cohort to test the newly established nomogram. Results: The overall incidence of 90-day poor outcomes was 45.16%, affecting 84 of 186 patients in the training set. Moreover, five variables, namely, age (odds ratio [OR]: 1.049, 95% CI [1.016-1.083]; p = 0.003), glucose level (OR: 1.163, 95% CI [1.038-1.303]; p = 0.009), baseline National Institute of Health Stroke Scale (NIHSS) score (OR: 1.066, 95% CI [0.995-1.142]; p = 0.069), unsuccessful recanalization (defined as a TICI grade of 0 to 2a) (OR: 3.730, 95% CI [1.688-8.245]; p = 0.001), and early neurological deterioration (END, defined as an increase of ≥4 points between the baseline NIHSS score and the NIHSS score at 24 h after MT) (OR: 3.383, 95% CI [1.411-8.106]; p = 0.006), were included in the nomogram to predict the potential risk of poor outcomes at 90 days following MT in LVO patients, with a C-index of 0.763 (0.693-0.832) in the training set and 0.804 (0.719-0.889) in the validation set. Conclusion: The proposed nomogram provided clinical evidence for the effective control of these risk factors before or during the process of MT surgery in LVO patients.

Safety and efficacy of endovascular recanalization in patients with mild anterior stroke due to large-vessel occlusion exceeding 24 hours.

BACKGROUND: Endovascular recanalization (ER) has demonstrated efficacy as a treatment modality for patients presenting with acute ischemic stroke (AIS) caused by large-vessel occlusion (LVO) within a 24-hour timeframe. Nevertheless, the safety and effectiveness of ER in patients with a time of onset exceeding 24 h remain uncertain. OBJECTIVE: To evaluate the safety and efficacy of ER treatment for mild ischemic stroke beyond 24-h from symptom onset. METHODS: A retrospectively maintained database of mild AIS due to LVO from March2018 to September 2022 at a comprehensive stroke center was screened.Patients received ER or standard medical therapies (SMT) for anterior circulation AIS due to LVO > 24-h were selected. RESULTS: We included 47 LVO patients with mild AIS beyond 24-h who suffered neurological deterioration (ND). 34 of these patients underwent ER, the other 13 received SMT. The technical success rate of recanalization was 82.4% (28/34). Patients received ER had significantly lower NIHSS score at discharge and 90-day mRS score (p = 0.028, p = 0.037, respectively) compared to SMT. In addition, they had significantly lower 90-day recurrence of ischemic stroke and lower incidence of moderate-severe stroke (with a NIHSS score at least 5) (p = 0.037, p = 0.033). There were 4 patients (11.7%) had perioperative complications, and no symptomatic intracranial hemorrhage occurred. CONCLUSION: ER treatment for mild AIS due to LVO encountered ND was generally safe and effective, even beyond 24-h, and resulted in a good prognosis and lower 90-day recurrence compared to SMT.

ER for mild anterior stroke might be safe and feasible, even exceeding 24-h;The proposed protocol could be used for individualized treatment decision making;Modelling for heterogeneity of treatment effect.

Predictors of Early Neurological Deterioration Occurring within 24 h in Acute Ischemic Stroke following Reperfusion Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: Early neurological deterioration (END), generally defined as the increment of National Institutes of Health Stroke Scale (NIHSS) score ≥4 within 24 hours, lead to poor clinical outcome in acute ischemic stroke (AIS) patients receiving reperfusion therapies including intravenous thrombolysis (IVT) and/or endovascular treatment (EVT). This systematic review and meta-analysis aimed to explore multiple predictors of END following reperfusion therapies. METHODS: We searched PubMed, Web of Science and EBSCO for all studies on END in AIS patients receiving IVT and/or EVT published between January 2000 and December 2022. A random-effects meta-analysis was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of each included studies was assessed by calculating a total score according to the STROBE or CONSORT criteria. Publication bias and heterogeneity were also evaluated using the Eggers/Peters test, funnel plots and sensitivity analysis. RESULTS: A total of 29 studies involving 65,960 AIS patients were included. The quality of evidence is moderate to high, and all studies have no publication bias. The overall incidence of END occurring after reperfusion therapy in AIS patients was 14% ((95% confidence intervals (CI), 12%-15%)). Age, systolic blood pressure (SBP), glucose levels at admission, the onset to treatment time (OTT), hypertension, diabetes mellitus, arterial fibrillation, and internal cerebral artery occlusion were significantly associated with END following reperfusion therapy. CONCLUSIONS: Numerous factors are associated with END occurrence in AIS patients receiving reperfusion therapy. Management of the risk factors of END may improve the functional outcome after reperfusion treatment.

Factors influencing the rate of residual stenosis in athletic patients after endovascular intervention for symptomatic carotid artery stenosis

Objective: High residual stenosis after endovascular treatment was a risk factor for postoperative stenosis in athletic patients with symptomatic carotid artery stenosis. This study investigated the factors influencing the residual stenosis rate after endovascular interventional therapy for symptomatic carotid artery stenosis.Methods: This study involved 337 athletic patients with symptomatic carotid artery stenosis (191 in a residual stenosis group and 186 in a non-residual stenosis group). To obtain differences in distribution between residual and non-residual stenosis groups, the variables of baseline information were dichotomized by median value and compared by chi-square test. In addition, we screened the categorical variables for each risk factor by a single-factor linear regression model and then determined the final influencing factors by the stepwise regression model.Results: Among the 377 athletic patients with symptomatic carotid artery stenosis, 191 (50.66%) developed residual stenosis after interventional recanalization procedures. Analysis of single-factor linear regression model showed that age and NLR were statistically significant (P<0.05) even during the continuous change in residual stenosis rate, and there was a positive correlation between them. Stepwise regression analysis showed that age and NLR were positive correlated with the occurrence of residual stenosis after excluding possible confounding factors, which was consistent with the results of the single-factor linear regression model (P<0.05).Conclusion: NLR, as a notable predictor of inflammation, had an important predictive value for the occurrence of residual stenosis after EVT. In addition, age of athletic patients also increased the risk of residual stenosis to some extent. (AU)

Significant improvement of procedural safety in stenting for basilar stenosis: A historically controlled study.

The basilar artery has the most perioperative complications in stenting compared to the other intracranial arteries. We aim to study whether the procedural safety in stenting for basilar stenosis has improved. This study was a single-arm, non-randomized trial that included historically controlled patients for comparison. Between January 2012 and March 2019, 147 consecutive patients with symptomatic basilar stenoses receiving elective stenting treatment were included in current basilar artery stenting (BAS) group. The prospectively collected and registered 120 patients by the same interventional team from September 2001 to November 2011 were set as historical BAS group for control. A total of 267 individuals were included in this study, with a mean age of 59.5 ±â€…8.1 years. The proportion of patients with lesion length >15 mm was 26.5% (39/147) in the current BAS group versus 4.2% (5/120) in the historical BAS group. We found significant differences between these 2 groups in Mori A (17.7% vs 42.5%) and Mori C patients (42.9% vs 13.3%). The proportion of patients receiving preoperative high-resolution magnetic resonance (HRMRI) evaluation was 83.0% (122/147) in the current BAS group versus 20.8% (25/120) in the historical group (P < .05). Balloon-expendable stent (BES) (n = 1), Wingspan (n = 34), and Enterprise (n = 112) stents were placed in the current BAS group. In contrast, only balloon-expendable stent (BES) (n = 48) and Wingspan (n = 72) were deployed in the historical BAS group. The incidence of the safety endpoint (SE) was 4.1% (involving 6 patients) in the current BAS group versus 11.7% (involving 14 patients) in the historical BAS group (P < .05). In multivariate analysis, no risk factor was associated with the occurrence of the safety endpoint (SE). When BAS cases operated by the surgical team accumulated to 120 to 150, the incidence of complications decreased significantly. This is the largest sample size study to discuss the safety of BAS. The significantly decreased incidence of complications indicates that the improving technical measures and the accumulation of operation experience are necessary.

Cardiotoxicity drug screening based on whole-panel intracellular recording.

Unintended binding of small-molecule drugs to ion channels affects electrophysiological properties of cardiomyocytes and potentially leads to arrhythmia and heart failure. The waveforms of intracellular action potentials reflect the coordinated activities of cardiac ion channels and serve as a reliable means for assessing drug toxicity, but the implementation is limited by the low throughput of patch clamp for intracellular recording measurements. In the last decade, several new technologies are being developed to address this challenge. We recently developed the nanocrown electrode array (NcEA) technology that allows robust, parallel, and long-duration recording of intracellular action potentials (iAPs). Here, we demonstrate that NcEAs allow comparison of iAP waveforms before and after drug treatment from the same cell. This self-referencing comparison not only shows distinct drug effects of sodium, potassium, and calcium blockers, but also reveals subtle differences among three subclasses of sodium channel blockers with sub-millisecond accuracy. Furthermore, self-referencing comparison unveils heterogeneous drug responses among different cells. In our study, whole-panel simultaneous intracellular recording can be reliably achieved with ∼94% success rate. The average duration of intracellular recording is ∼30 min and some last longer than 2 h. With its high reliability, long recording duration, and easy-to-use nature, NcEA would be useful for iAP-based preclinical drug screening.

Predictors of ninety-day mortality following mechanical thrombectomy for acute large vessel occlusion stroke.

OBJECTIVE: This study focused on the prediction factors of catastrophic outcomes of all-cause mortality at 90 days after mechanical thrombectomy and selection of candidates for clinical decision making up by the generating pre-MT and peri-MT prognostic models. METHOD: A secondary analysis based on the prospective, multicenter, randomized, non-inferiority clinical trial of Jrecan retriever from China were performed in this study. 187 stroke patients with a large-vessel anterior circulation occlusion, NIHSS score ≥ 6, ASPECT ≥ 7, and stroke onset time within 8 h were enrolled from March 1, 2018 to June 30, 2019 and followed up for 90 days. Data with mRS cumulative rates of 6, as well as mortality were analyzed and potential predictors for the mortality risk were identified by univariate and multivariate regression analysis. RESULTS: Among 186 patients, the median age was 66 years (IQR, 58-74) and 106 patients (56.4%) were male. The mortality was 20.8% (39/186) and general favorable outcome was obtained in 78 patients (41.7%, 78/187) at 90 days after MT. Five variables including ASPECT≤ 9 (3.136 [1.239-7.939], P = 0.016), Occlusion location with IC-ICA (3.538 [1.604-7.803], P = 0.002), un-Successful recanalization; PH (7.644 [1.890-30.917], P = 0.004), and END (without PH) with a significance of P < 0.05 were entered into the multivariable logistic regression analysis and were incorporated into pre-procedure model and peri-procedure models respectively. CONCLUSIONS: Occlusion with IC-ICA and PH were the strong predictors for mortality risk at 90-day, which could be reduced through good management and evaluation during pre-procedure and peri-procedure of mechanical thrombectomy.

Nanocrown electrodes for parallel and robust intracellular recording of cardiomyocytes.

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. However, the large variability in success rate and signal strength have hindered nanoelectrodes from being broadly adopted for proarrhythmia drug assessment. In this work, we develop vertically-aligned nanocrown electrodes that are mechanically robust and achieve > 99% success rates in obtaining intracellular access through electroporation. We validate the accuracy of nanocrown electrode recordings by simultaneous patch clamp recording from the same cell. Finally, we demonstrate that nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four incremental drug doses. Our technology development provides an advancement towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.

The Jrecan Device: Preclinical Data of a Novel Thrombectomy Device in Acute Thromboembolism Model of Beagle Dogs.

Objective: The aim of this study is to investigate the safety and efficiency of a Jrecan® flow restoration system, a novel thrombectomy device, in an arterial thromboembolic occlusion model of Beagle dogs. Methods: A total of 12 Beagle dogs with acute thromboembolism were randomized to receive mechanical thrombectomy with either Jrecan® flow restoration device or TrevoTM PROVUE Device (2:1). The efficacy and safety of the two devices, including recanalization rate, the presence of distal embolism, vasospasm, vessel perforation, and vessel injuries were evaluated through DSA and microscopic examination. Result: A 100% recanalization rate (mTICI 2b/3) was achieved in both groups. Endothelial and subendothelial injuries occurred in all target vessels. Focal disruption of internal elastic lamina was observed in 4 cases. The mean vessel injury score of the Jrecan® group was 1.16 ± 0.48, significantly lower than that of the TrevoTM group (1.54 ± 0.8) (P < 0.001). Conclusion: The Jrecan® and TrevoTM devices demonstrated an equally high recanalization rate in Beagle dogs with acute thromboembolism. However, histological findings revealed that the Jrecan® stent seemed to be safer than the TrevoTM device during clot retrieval, which might be related to a more appropriate radial force provided by the Jrecan® stent that resulted from its wider cell design.

MRI radiomic features-based machine learning approach to classify ischemic stroke onset time.

PURPOSE: We aimed to investigate the ability of MRI radiomics features-based machine learning (ML) models to classify the time since stroke onset (TSS), which could aid in stroke assessment and treatment options. METHODS: This study involved 84 patients with acute ischemic stroke due to anterior circulation artery occlusion (51 in the training cohort and 33 in the independent test cohort). Region of infarct segmentation was manually outlined by 3D-slicer software. Image processing including registration, normalization and radiomics features calculation were done in R (version 3.6.1). A total of 4312 radiomic features from each image sequence were captured and used in six ML models to estimate stroke onset time for binary classification (≤ 4.5 h). Receiver-operating characteristic curve (ROC) and other parameters were calculated to evaluate the performance of the models in both training and test cohorts. RESULTS: Twelve radiomics and six clinic features were selected to construct the ML models for TSS classification. The deep learning model-based DWI/ADC radiomic features performed the best for binary TSS classification in the independent test cohort, with an AUC of 0.754, accuracy of 0.788, sensitivity of 0.952, specificity of 0.500, positive predictive value of 0.769, and negative predictive value of 0.857, respectively. Furthermore, adding clinical information did not improve the performance of the DWI/ADC-based deep learning model. The TSS prediction models can be visited at: http://123.57.65.199:3838/deeptss/ . CONCLUSIONS: A unique deep learning model based on DWI/ADC radiomic features was constructed for TSS classification, which could aid in decision making for thrombolysis in patients with unknown stroke onset.

Recanalization Treatment of Acute Ischemic Stroke Caused by Large-Artery Occlusion in the Elderly: A Comparative Analysis of "the Elderly" and "the Very Elderly".

OBJECTIVE: To assess whether the effectiveness and safety of recanalization therapy for acute ischemic stroke (AIS) caused by large-artery occlusion (LAO) differ between patients aged 60-79 years and patients aged ≥80 years. METHODS: We analyzed prospective data of patients with LAO (≥60 years) who underwent recanalization therapy at the Department of Vascular Neurosurgery, New Era Stroke Care and Research Institute, PLA Rocket Force Characteristic Medical Center, from November 2013 to July 2017. The data were compared between elderly patients (60-79 years) and very elderly patients (≥80 years). The effectiveness of recanalization therapy was evaluated using the 90-day modified Rankin scale (mRS) score, while safety was assessed by the rates of symptomatic intracranial hemorrhage (SICH) and mortality within 30 days. RESULTS: A total of 151 patients with AIS induced by LAO were included in this study. Seventy-three patients (48.3% [73/151]) had an overall favorable outcome (mRS score 0-2) after treatment. A higher proportion of patients in the elderly group showed a favorable outcome compared with the very elderly group (58.6% [34/58] vs. 41.6% [39/93], respectively; P = 0.046). The incidence of SICH (12.7% vs. 16.13%, respectively; P = 0.561) and mortality (10.3% vs. 7.5%, respectively; P = 0.548) within 30 days was not significantly different between the two groups. CONCLUSION: Recanalization treatment of LAO is more effective in elderly patients compared with very elderly patients, while the safety of recanalization treatment is comparable between these two groups.

Susceptibility-diffusion mismatch correlated with leptomeningeal collateralization in large vessel occlusion stroke.

OBJECTIVE: To investigate the relationship between asymmetric prominent hypointense vessels (prominent vessel sign, PVS) on susceptibility-weighted imaging (SWI) and leptomeningeal collateralization in patients with acute ischemic stroke due to large vessel occlusion. METHODS: We retrospectively enrolled patients with M1 segment occlusion of the middle cerebral artery who underwent emergency magnetic resonance imaging and digital subtraction angiography within 24 hours from stroke onset. The extent of PVS on SWI was assessed using the Alberta Stroke Program Early CT Score (ASPECTS). Leptomeningeal collateralization on digital subtraction angiography images was assessed using the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) scale. Spearman's rank correlation test was performed to explore the correlation of ASITN/SIR scores with SWI-ASPECTS and SWI-diffusion-weighted imaging (DWI) mismatch scores. RESULTS: Thirty-five patients were enrolled. There was no significant correlation between SWI-ASPECTS and ASITN/SIR scores. However, SWI-DWI mismatch scores were positively correlated with ASITN/SIR scores. CONCLUSION: The range of PVS on SWI did not closely reflect the collateral status, while the range of SWI-DWI mismatch was significantly correlated with the leptomeningeal collateralization. In patients with acute anterior circulation stroke due to large vessel occlusion, larger SWI-DWI mismatch was associated with better leptomeningeal collaterals.

Perforator preservation technologies (PPT) based on a new neuro-interventional classification in endovascular treatment of perforator involving aneurysms (piANs).

BACKGROUND: Treatment of perforator involving aneurysm (piAN) remains a challenge to open and endovascular neurosurgeons. Our aim is to demonstrate a primary outcome of endovascular therapy for piANs with the use of perforator preservation technologies (PPT) based on a new neuro-interventional classification. METHODS: The piANs were classified into type I: aneurysm really arises from perforating artery, type II: saccular aneurysm involves perforating arteries arising from its neck (IIa) or dome (IIb), and type III: fusiform aneurysm involves perforating artery. Stent protection technology of PPT was applied in type I and III aneurysms, and coil-basket protection technology in type II aneurysms. An immediate outcome of aneurysmal obliteration after treatment was evaluated (satisfactory obliteration: the saccular aneurysm body is densely embolized (I), leaving a gap in the neck (IIa) or dome (IIb) where the perforating artery arising; fusiform aneurysm is repaired and has a smooth inner wall), and successful perforating artery preservation was defined as keeping the good antegrade flow of those perforators on postoperative angiography. The periprocedural complication was closely monitored, and clinical and angiographic follow-ups were performed. RESULTS: Six consecutive piANs (2 ruptured and 4 unruptured; 1 type I, 2 type IIa, 2 type IIb, and 1 type III) in 6 patients (aged from 43 to 66 years; 3 males) underwent endovascular therapy between November 2017 and July 2019. The immediate angiography after treatment showed 6 aneurysms obtained satisfactory obliteration, and all of their perforating arteries were successfully preserved. During clinical follow-up of 13-50 months, no ischemic or hemorrhagic event of the brain occurred in the 6 patients, but has one who developed ischemic event in the territory of involving perforators 4 h after operation and completely resolved within 24 h. Follow-up angiography at 3 to 10M showed patency of the parent artery and perforating arteries of treated aneurysms, with no aneurysmal recurrence. CONCLUSIONS: Our perforator preservation technologies on the basis of the new neuro-interventional classification seem feasible, safe, and effective in protecting involved perforators while occluding aneurysm.

Factors associated with prominent vessel sign on susceptibility-weighted imaging in acute ischemic stroke.

The prominent vessel sign (PVS) on susceptibility-weighted imaging (SWI) is not displayed in all cases of acute ischemia. We aimed to investigate the factors associated with the presence of PVS in stroke patients. Consecutive ischemic stroke patients admitted within 24 h from symptom onset underwent emergency multimodal MRI at admission. Associated factors for the presence of PVS were analyzed using univariate analyses and multivariable logistic regression analyses. A total of 218 patients were enrolled. The occurrence rate of PVS was 55.5%. Univariate analyses showed significant differences between PVS-positive group and PVS-negative group in age, history of coronary heart disease, baseline NIHSS scores, total cholesterol, hemoglobin, anterior circulation infarct, large vessel occlusion, and cardioembolism. Multivariable logistic regression analyses revealed that the independent factors associated with PVS were anterior circulation infarct (odds ratio [OR] 13.7; 95% confidence interval [CI] 3.5-53.3), large vessel occlusion (OR 123.3; 95% CI 33.7-451.5), and cardioembolism (OR 5.6; 95% CI 2.1-15.3). Anterior circulation infarct, large vessel occlusion, and cardioembolism are independently associated with the presence of PVS on SWI.

Dissection-related carotid-cavernous fistula (CCF) following surgical revascularization of chronic internal carotid artery occlusion: a new subtype of CCF and proposed management.

BACKGROUND: The development of carotid-cavernous fistulas (CCFs) during surgical recanalization of chronic internal carotid artery occlusion (ICAO) may be secondary to severe ICA dissection rather than a focal tear of the cavernous ICA seen in typical traumatic CCFs. The purpose of this study is to investigate the causal relationship between the CCFs and severe ICA dissections and to characterize technical outcomes after treatment with stenting. METHODS: Five patients underwent treatment with self-expanding stents due to intraprocedural CCF and ICA dissection following surgical removal of ICAO plaque. The stents were telescopically placed via true channel of the dissection. Safety of the procedure was evaluated with 30-day stroke and death rate. Procedural success was determined by the efficacy of CCF obliteration and ICAO recanalization with angiography. RESULTS: All CCFs were associated with spiral and long segmental dissection from the cervical to cavernous ICA. After stenting, successful dissection reconstruction with TICI 3 was achieved in all patients, with complete (n = 4) or partial CCF (n = 1) obliteration. No patient had CCF syndrome, stroke, or death during follow-up of 6 to 37 months; but one patient had pulsatile tinnitus, which resolved 1 year later. Angiography at 6 to 24 months demonstrated CCF obliteration in all 5 patients and durable ICA patency in 4 patients. CONCLUSIONS: Intraprocedural CCFs with spiral and cervical-to-cavernous ICA dissection during ICAO surgery are dissection-related because of successful obliteration after stenting for dissection reconstruction. Self-expanding stenting through true channel of the dissection, serving as implanting stent-autograft, may be an optimal therapy for the atypical CCF complication from ICAO surgery.

Molecular mechanism of long-term neuroprotective effects of gradual flow restoration on cerebral ischemia reperfusion injury in MCAO rats.

BACKGROUND AND PURPOSE: Ischemia-reperfusion injuries (IRIs) can aggravate the condition of some patients with acute occlusion of major intracranial artery (AOMIA) who received endovascular thrombectomy. Here, we provided data confirming the association of Repressor Element-1 Silencing Transcription factor (REST) with the long-term neuroprotective effect of the middle cerebral artery occlusion (MCAO) rats underwent Gradual Flow Restoration (GFR). METHODS: Long term neuroprotective effects of GFR intervention were evaluated on MCAO rats model after 3d and 7d reperfusion. The neurological deficit score and TTC staining were performed to evaluate the degree of brain damage in GFR and other interventions at different time. Differentially expressed genes related to cerebral ischemia reperfusion injury (CIRI) were initially screened and identified using GSE32529 microarray analysis. REST protein expression in rat brain cortex infarction was detected by Western blot analysis. RESULTS: MCAO rats intervened with GFR exhibited reduced neurological deficit (P < 0.05) and alleviated brain infarction volume (P < 0.01). The REST gene with up-regulated expression and its downstream genes with down-regulated expression were screened by Microarray analysis. The brain cortex infarction in MCAO rats produced high levels of REST expression. The GFR intervention inhibited REST expression, and alleviated brain injury on MCAO rats. CONCLUSION: Our results demonstrated that GFR intervention plays a long-term neuroprotective role and reduces brain edema and damage at reperfusion, possibly by inhibiting REST expression.