Background
Collateral therapeutics exert a promising protective effect on the outcome of acute ischemic stroke. Cerebral blood flow (CBF) may be modulated by different head positioning. The current ...study aimed to determine the effect of head‐down tilt (HDT) on stroke in a rodent model.
Methods
The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was used in this study. Neurological deficit scoring, 2,3,5‐triphenyltetrazolium chloride staining, brain water content, perivascular aquaporin protein‐4 (AQP4) localization, pericyte marker platelet‐derived growth factor receptor β (PDGFRβ), and CBF velocity were evaluated at 24 h after MCAO/R and HDT treatment.
Results
In the rat model of MCAO/R, brain infarct volume and neurological deficit score were significantly alleviated in the −30° and −60° groups compared to those in the lying flat (0°) group. Compared with the 0° group, an increase in CBF velocity was detected in the −30° group through two‐photon microscopy imaging at 24 h after MCAO/R. Compared with the SHAM group, a decrease in PDGFRβ was observed in both the MCAO/R and HDT treatment (−30°) groups. The integrated optical density of PDGFRβ was found to be higher in the HDT treatment (−30°) group than in the MCAO/R group. An impairment in perivascular AQP4 polarity and an increase in brain water content were observed after MCAO/R, which were not exacerbated by HDT treatment (−30°).
Conclusions
Our findings suggest that HDT treatment at certain degrees may exert a neuroprotective effect after MCAO/R through improving CBF velocity and the protection of pericytes.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Objective
Cerebral circulation time (CCT) and collateral score (CS) are associated with functional outcomes in acute ischemic stroke (AIS) patients after endovascular treatment (EVT), and may be ...related to each other. We aim to determine the relationship between CS and CCT on functional outcomes.
Methods
We retrospectively enrolled consecutive patients with anterior circulation large vessel occlusion (LVO) AIS who received EVT. CS and CCT were measured based on digital subtraction angiography (DSA). We defined CS 0–2 and 3–4 as poor and good collateral status, respectively, and used change of CCT (cCCT), which was defined as the change of stroke side CCT (sCCT) versus healthy side CCT (hCCT). Mediating analysis was used to evaluate the influence of cCCT on the association between CS and functional outcomes, and ROC curves were further used to explore the predictive ability of the interaction between cCCT and CS for functional outcomes.
Results
A total of 100 patients were enrolled in the final analysis. A higher cCCT (r = −0.239; p = 0.017) was associated with lower CS, and cCCT mediated the association of CS with functional outcome. Logistic regression analysis found that CS, cCCT and cCCT‐CS interactions were independently associated with functional outcome, and cCCT‐CS interaction has better predictive performance, with a higher area under curve value than CS or cCCT alone (0.79 vs. 0.75 or 0.75).
Interpretation
To our knowledge, this study provides the first report of the association of collateral status with cCCT, and their interaction effect on functional outcome in AIS‐LVO patients receiving EVT.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Contrast enhancement (CE) on brain non-contrast computed tomography (NCCT) is common after endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS), but its association with ...clinical outcomes is not well established. The current study aimed to investigate this relationship. We retrospectively reviewed consecutive patients with acute ischemic stroke who had hyperdensity on NCCT immediately after EVT for anterior circulation large vessel occlusion (LVO) from January 2016 to December 2019. We used ASPECTS combined with volume measurement by 3D reconstruction to estimate the extent and location of CE. Multivariable regression analysis was conducted to explore the risk factors associated with clinical outcome. In this study, 113 of 158 (71.52%) anterior circulation AIS-LVO patients had hyperdensity on brain NCCT. After strict inclusion and exclusion criteria, a total of 64 patients were enrolled in the final analysis. In logistic regression analysis, CE-ASPECTS, CE volume, CE at the caudate nucleus, M4 and M6 region were associated with 3-month poor functional outcome after adjusting for confounding factors. The conventional variable model was used for reference, including age, initial NIHSS, the procedure time, stent retriever passes, recanalization status and baseline ASPECTS, with AUC of 0.73. When combined with the above-named variables (conventional variables + CE-ASPECTS + CE volume + CE at caudate nucleus + CE at M4 region + CE at M6 region), the predictive power was significantly improved, with AUC of 0.87 (95% CI 0.78-0.95). The spatial location and volume of CE on NCCT obtained immediately after EVT were independent and strong predictors for poor outcome at 3-months in patients with AIS after excluding definite hemorrhage by 24-h follow up CT.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background Despite successful recanalization, up to half of patients with acute ischemic stroke caused by large-vessel occlusion treated with endovascular treatment (EVT) do not recover to functional ...independence. We aim to evaluate the role of cerebral circulation time (CCT) as outcome predictor after EVT. Methods and Results We retrospectively enrolled consecutive patients with acute ischemic stroke-large-vessel occlusion undergoing EVT. Three categories of CCT based on digital subtraction angiography were studied: CCT of the stroke side, CCT of the healthy side), and change of CCT of the stroke side versus CCT of the healthy side. Dramatic clinical recovery was defined as a 24-hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Logistic regression analysis was performed to evaluate the prediction of CCT on prognosis. One hundred patients were enrolled, of which 38 (38.0%) experienced a dramatic clinical recovery and 43 (43.0%) achieved a favorable outcome. Logistic regression analysis found that shorter change of CCT of the stroke side versus CCT of the healthy side and CCT of the stroke side were independent positive prognostic factors for dramatic clinical recovery (odds ratio OR, 0.189;
=0.033; OR, 0.581;
=0.035) and favorable outcomes (OR, 0.142;
=0.020; OR, 0.581;
=0.046) after adjustment for potential confounders. A model including the change of CCT of the stroke side versus CCT of the healthy side also had significantly higher area under the curve values compared with the baseline model in patients with dramatic clinical recovery (0.780 versus 0.742) or favorable outcome (0.759 versus 0.713). Conclusions To our knowledge, this is the first report that CCT based on digital subtraction angiography data exhibits an independent predictive performance for clinical outcome in patients with acute ischemic stroke-large-vessel occlusion after EVT. Given that this readily available CCT can provide alternative perfusion information during EVT, a prospective, multicenter trial is warranted.
The aim of the study was to establish a reliable scoring tool to identify the probability of symptomatic intracranial hemorrhage (sICH) in anterior circulation stroke patients with contrast ...enhancement (CE) on brain non-contrast CT (NCCT) after endovascular thrombectomy (EVT).
We retrospectively reviewed consecutive patients with acute ischemic stroke (AIS) who had CE on NCCT immediately after EVT for anterior circulation large vessel occlusion (LVO). We used the Alberta stroke program early CT score (ASPECTS) scoring system to estimate the extent and location of CE. Multivariable logistic regression was performed to derive an sICH predictive score. The discrimination and calibration of this score were assessed using the area under the receiver operator characteristic curve, calibration curve, and decision curve analysis.
In this study, 194 of 322 (60.25%) anterior circulation AIS-LVO patients had CE on NCCT. After excluding 85 patients, 109 patients were enrolled in the final analysis. In multivariate regression analysis, age ≥70 years (adjusted OR (aOR) 9.23, 95% CI 2.43 to 34.97, P＜0.05), atrial fibrillation (AF) (aOR 4.17, 95% CI 1.33 to 13.12, P＜0.05), serum glucose ≥11.1 mmol/L (aOR 9.39, 95% CI 2.74 to 32.14, P＜0.05), CE-ASPECTS ＜5 (aOR 3.95, 95% CI 1.30 to 12.04 P＜0.05), and CE at the internal capsule (aOR 3.45, 95% CI 1.03 to 11.59, P＜0.05) and M1 region (aOR 3.65, 95% CI 1.13 to 11.80, P＜0.05) were associated with sICH. These variables were incorporated as the CE-age-glucose-AF (CAGA) score. The CAGA score demonstrated good discrimination and calibration in this cohort, as well as the fivefold cross validation.
The CAGA score reliably predicted sICH in patients with CE on NCCT after EVT treatment.
In microglia, Toll-like receptor 4 (TLR4) is well known to contribute to neuroinflammatory responses following brain ischemia. TLR4 is also expressed in neurons and can mediate the conduction of ...calcium (Ca
2+
) influx, but the mechanistic link between neuronal TLR4 signaling and brain ischemic injury is still poorly understood. Here, primary neuronal cell cultures from TLR4 knockout mice and mice with conditional TLR4 knockout in glutamatergic neurons (TLR4
cKO
) were used to establish ischemic models in vitro and in vivo, respectively. We found that deleting TLR4 would reduce the neuronal death and intracellular Ca
2+
increasement induced by oxygen and glucose deprivation (OGD) or lipopolysaccharide treatment. Infarct volume and functional deficits were also alleviated in TLR4
cKO
mice following cerebral ischemia/reperfusion (I/R). Furthermore, TLR4 and N-methyl-
d
-aspartate receptor subunit 2B (NMDAR2B) were colocalized in neurons. Deletion of TLR4 in neurons rescued the upregulation of phosphorylated NMDAR2B induced by ischemia via Src kinase in vitro and in vivo. Downstream of NMDAR2B signaling, the interaction of neuronal nitric oxide synthase (nNOS) with postsynaptic density protein-95 (PSD-95) was also disrupted in TLR4
cKO
mice following cerebral I/R. Taken together, our results demonstrate a novel molecular neuronal pathway in which TLR4 signaling in neurons plays a crucial role in neuronal death and provide a new target for neuroprotection after ischemic stroke.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The in-hospital mortality of severe pulmonary hypertension (PH) with right heart failure (RHF) is high despite the use of vasoactive and PH-specific therapies. We conducted a prospective analysis ...evaluating the safety and outcomes of fasudil hydrochloride (Chuan Wei) therapy in acute RHF. PH patients hospitalized between April 2009 and November 2010 were treated with 30 mg of i.v. fasudil three times daily over 30 min, until they experienced relief of RHF symptoms. Adverse and serious adverse events were recorded. Odds ratios (ORs) and 95% confidence intervals were calculated for both in-hospital mortality and re-hospitalization. Multivariate adjustments were made for age, gender and World Health Organization functional class. There were no significant differences between the fasudil group and the control group in demographics, hemodynamics, and PH-specific and vasoactive therapies. Of the 209 study patients, 3 of the 74 patients (4.1%) in the fasudil arm died, and 19 of the 135 patients (14.1%) in the control arm died (P=0.005). Fasudil decreased both in-hospital mortality (OR=0.258 (0.074-0.903); P=0.034) and 30-day re-hospitalization (OR=0.200 (0.059-0.681); P=0.010). Fasudil was well tolerated; one patient discontinued treatment. Intravenous fasudil may be given safely in patients with PH and acute RHF, and may reduce the rates of both in-hospital mortality and 30-day re-hospitalization.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Traumatic brain injury (TBI) can induce cognitive dysfunction due to the regional accumulation of hyperphosphorylated tau protein (p-tau). However, the factors that cause p-tau to ...concentrate in specific brain regions remain unclear. Here, we show that AQP4 polarization in the perivascular astrocytic end feet was impaired after TBI, which was most prominent in the ipsilateral brain tissue surrounding the directly impacted region and the contralateral hippocampal CA1 area and was accompanied by increased local p-tau, changes in dendritic spine density and morphology, and upregulation of the adenosine A
2A
receptor (A
2A
R). The critical role of the A
2A
R signaling in these pathological changes was confirmed by alleviation of the impairment of AQP4 polarity and accumulation of p-tau in the contralateral CA1 area in A
2A
R knockout mice. Given that p-tau can be released to the extracellular space and that the astroglial water transport via AQP4 is involved in tau clearance from the brain interstitium, our results suggest that regional disruption of AQP4 polarity following TBI may reduce the clearance of the toxic interstitial solutes such as p-tau and lead to changes in dendritic spine density and morphology. This may explain why TBI patients are more vulnerable to cognitive dysfunction.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Characterizing the emission performance of formaldehyde is critical for control strategies. Most previous emission models assume that formaldehyde concentrations are well-mixed. In this study, a ...computational fluid dynamics-based model is developed for simulating the mass transfer and adsorption/desorption processes of formaldehyde from particleboards in a chamber with a mixing fan. Numerical investigations on the impacts of the mixing fan, adsorption/desorption rate constants, and key transport parameters influencing the emission behaviors are conducted for the first time. The results show that the complete mixing assumption is not appropriate in the early emission period. Incomplete mixing becomes more significant with a decreasing rotation speed, leading to a time-dependent equivalent mass transfer coefficient. The deviation in the maximum concentration between the simulated curves with and without the adsorption/desorption effect is approximately 8.5%. A coefficient of mixing of 0.0283 is suitable for evaluating complete mixing in the chamber. With an increase in the rotation speed, the degree of mixing improves, and the mass transfer coefficient increases sub-linearly. Secondary reemission becomes more significant and begins earlier for materials with lower partition coefficients and higher diffusivity.
•A 3D model considering the whole transport processes of formaldehyde is proposed.•Impact of the fan on the mixing degree and mass transfer coefficient is revealed.•Incomplete mixing in the early period governed by circulation current is observed.•Emission profiles are sensitive to the degree of mixing and the ventilation rate.•The adsorption/desorption behaviors are affected by the key transport parameters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The first-pass recanalization of endovascular treatment (EVT) is closely correlated with clinical outcome of patients with large vessel occlusion (LVO) stroke. The aim of the study was to explore ...whether intra-arterial tenecteplase (TNK) during the first pass of EVT can increase first-pass successful reperfusion and improve the neurological outcome in AIS-LVO patients.
The BRETIS-TNK trial (ClinicalTrials.gov Identifier: NCT04202458) was a prospective, single-arm, single center study. Twenty-six eligible AIS-LVO patients with large-artery atherosclerosis etiology were consecutively enrolled from December 2019 to November 2021. Intra-arterial TNK (4 mg) after microcatheter navigation through the clot was administered, followed by TNK (0.4 mg/min) given continuously for 20 min after the first retrieval attempt of EVT without confirmation of the reperfusion status by DSA. The 50 control patients comprised of a historical cohort before the BRETIS-TNK trial (from March 2015 to November 2019). Successful reperfusion was defined as modified Thrombolysis In Cerebral Infarction (mTICI) ≥2b.
The first-pass successful reperfusion rate was higher in the BRETIS-TNK vs. control group (53.8% vs. 36%,
= 0.14), and the difference became statistically significant after propensity score matching (53.8% vs. 23.1%,
= 0.03). There was no difference in symptomatic intracranial hemorrhage between the BRETIS-TNK and control groups (7.7% vs. 10.0%,
= 0.92). There was a trend toward higher proportion of functional independence at 90 days in the BRETIS-TNK comparing with the control group (50% vs. 32%,
= 0.11).
This is the first study to report that intra-arterial TNK during the first pass of EVT seems safe and feasible in AIS-LVO patients.
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