Current Neurovascular Research - Online First

This study aimed to explore Malignant Brain Edema (MBE) and associated factors in patients with Large Hemispheric Infarction (LHI) following early reperfusion therapy.

We consecutively and retrospectively enrolled a cohort of 114 LHI patients who had received early reperfusion therapy, including Intravenous Thrombolysis (IVT) or Endovascular Therapy (EVT) at the hyperacute stage of stroke between January 2009 and December 2018. MBE was defined as a midline shift ≥5 mm, accompanied by signs of herniation. Multivariate logistic analyses were conducted to identify independent factors associated with MBE in LHI patients following early reperfusion therapy.

Among the enrolled patients, 69 (60.53%) were treated with IVT alone and 45 (39.47%) with EVT. Successful recanalization was achieved in 56 (49.12%) patients, while complete recanalization was achieved in 38 (33.33%) patients. After early reperfusion therapy, 50 (43.86%) developed MBE in LHI patients. The MBE group showed higher rates of in-hospital death (54% vs. 4.69%), 3-month mortality (64% vs. 10.94%), and 3-month unfavorable outcomes (90% vs. 64.06%) (all p<0.01). Neither different reperfusion therapy (EVT vs. IVT alone) nor different recanalization status (complete recanalization or not) was independently associated with the development of MBE in LHI patients following reperfusion therapy in multivariate analyses. MBE was independently associated with age [Odds Ratio (OR) 0.953, 95% confidence interval (CI) 0.910-0.999, p =0.044], right hemisphere stroke (OR 4.051, 95% CI 1.035-15.860, p =0.045), previous ischemic stroke or TIA (OR 0.090, 95% CI 0.014-0.571, p =0.011), and hypodensity >1/3 MCA territory (OR 8.071, 95% CI 1.878-34.693, p =0.005). Meanwhile, patients with lower baseline Alberta Stroke Program Early CT Score (ASPECTS) had a trend of higher incidence of MBE following reperfusion therapy (OR 0.710, 95% CI 0.483-1.043, p =0.081).

MBE occurred in nearly one-half of LHI patients following early reperfusion therapy and was related to poor outcomes. An increased risk of MBE was found to be associated with younger age, right hemisphere stroke, absence of a history of ischemic stroke or TIA, and hypodensity >1/3 MCA region on baseline CT images.

Intracranial Atherosclerotic Stenosis (ICAS) is a prevalent etiology of acute ischemic stroke (AIS), leading to significant morbidity and mortality. The accurate diagnosis and treatment of ICAS-induced AIS are critical to improving outcomes. This study assesses the application of Computed Tomography Perfusion (CTP) in predicting ICAS in AIS patients and its potential impact on patient management.

A retrospective analysis was conducted on 224 AIS patients who underwent endovascular therapy (EVT) at one single Chinese Stroke Center between April 2022 and December 2023. Clinical and radiological data were collected, including patients’ demographics, CTP parameters, and 90-day modified Rankin Scale (mRS) scores. Logistic regression and receiver operating characteristic (ROC) curves evaluated the predictive power of CTP parameters for ICAS.

CTP analysis revealed significant differences in perfusion parameters between ICAS-induced AIS and other etiologies. ICAS patients had a smaller ischemic volume on admission and higher mismatch ratios [Time to Maximum, Tmax>6s: Other Causes: 132.4 [70.5, 183.3] mL, ICAS: 96.3 [79.8, 107.3] mL, P=0.0064; relative cerebral blood flow, rCBF<30%: Other Causes: 2.4 [0.0, 10.8] mL, ICAS: 0.6 [0.0, 7.0] mL, p =0.0145; mismatch ratio: 7.4 [2.5, 15.0], ICAS: 11.0 [4.6, 17.8], p =0.0285], indicating more salvageable brain tissue. The 90-day mRS showed better functional outcomes in the ICAS group, with a higher likelihood of minimal to no disability [mRS 90 equals 0-1: ICAS: 53.0% vs. Other Causes: 36.3%, p =0.0122]. The predictive model for ICAS, combining clinical manifestations and CTP parameters, yielded an area under the curve (AUC) of 0.7779, demonstrating good diagnostic performance.

CTP is a valuable diagnostic tool for ICAS-induced AIS, offering the potential for early identification and informing the decision for endovascular treatment. The positive correlation between CTP findings and patient outcomes supports its utility in clinical practice.

The aim of this study was to explore the primary changes in corneal nerve fiber structure and its influencing factors in patients with primary glaucoma.

A retrospective analysis was conducted in this study. A total of 51 patients with primary glaucoma who were diagnosed and treated in our hospital from March 2020 to March 2022 were selected as the research objects and designated as the glaucoma group. In addition, 51 patients with normal eyes were chosen as the control group. The characteristic changes of corneal nerve fibers, the thickness of the nerve fiber layer, and the number of ganglion cell complexes and dendritic cells were measured. Multivariate logistic regression analysis was performed to analyze the influencing factors of ganglion fiber structure change.

Compared with the control group, the length of corneal nerve fibers and the density of corneal nerve fibers in the glaucoma group were significantly shortened, the number of branches was significantly reduced, the curvature was significantly increased, and the number of dendritic cells was significantly increased (P <0.05). Compared with the control group, the thickness of the upper, lower, nasal, temporal, and peripheral nerve fiber layers in the glaucoma group was obviously reduced (P <0.05). Compared with the control group, the thickness of the above inferior, nasal, temporal, and peripheral nerve fiber layers in the glaucoma group was significantly reduced (P <0.05). Compared with the control group, the above, below, and mean ganglion cell complex thickness in the glaucoma group was significantly reduced (P <0.05). Logistic regression analysis showed that intraocular pressure and the number of dendritic cells were risk factors for ganglion fiber structure change. In contrast, nerve fiber layer thickness and ganglion cell complex were protective factors for ganglion fiber structure change (P <0.05).

There were primary changes in the structure of corneal nerve fibers in patients with primary glaucoma, which were more slender, tortuous, and sparse, and the primary changes in nerve fiber structure could be affected by intraocular pressure, the number of dendritic cells, the thickness of the nerve fiber layer, and the ganglion cell complex.

Electroacupuncture (EA) exerts a protective role in Blood-Brain Barrier (BBB) damage after ischemic stroke, but whether this effect involves the regulation of the pericytes in vitro is unclear.

The in vitro BBB models were established with brain microvascular endothelial cells (BMECs) and pericytes, and the co-cultured cells were randomly divided into three groups: the control group, oxygen-glucose deprivation/reoxygenation (OGD/R) group and EA group. OGD/R was performed to simulate cerebral ischemia-reperfusion in vitro. EA serum was prepared by EA treatment at the “Renzhong” (GV26) and “Baihui” (GV20) acupoints in middle cerebral artery occlusion/reperfusion rats. Furthermore, the characteristics of BMECs and pericytes were identified with immunohistochemistry staining. The cell morphology of the BBB model was observed using an inverted microscope. The function of BBB was measured with transendothelial electrical resistance (TEER) and sodium fluorescein, and the viability, apoptosis, and migration of pericytes were detected by cell counting kit-8, flow cytometry, and Transwell migration assay.

BMECs were positive staining for Factor-VIII, and pericytes were positive staining for the α-SMA and NG2. EA serum improved cell morphology of the BBB model increased TEER, and decreased sodium fluorescein in OGD/R condition. Besides, EA serum alleviated pericytes” apoptosis rate and migration number, and enhanced pericytes' viability rate in OGD/R condition.

EA serum protects against BBB damage induced by OGD/R in vitro, and this protection might be achieved by attenuating pericytes apoptosis and migration, as well as enhancing pericytes viability. The findings provided new evidence for EA as a medical therapy for ischemic stroke.

To explore the effect of baseline Systemic Inflammatory Response reflected by platelet-to-lymphocyte ratio (PLR) and pre-thrombectomy cerebral edema reflected by Net Water Uptake (NWU) on futile recanalization in patients with Acute Ischemic Stroke (AIS) after successful thrombectomy, and to investigate the potential mediating role of baseline cerebral edema.

134 Patients with anterior circulation ischemic stroke receiving successful thrombectomy were retrospectively studied. Their demographic and clinical characteristics were collected at admission, and the NWU was quantitatively calculated based on baseline computed tomography (CT). The predictive value of PLR for futile recanalization and the relationship between PLR, NWU, and futile recanalization using mediation analysis were explored. Patients were followed up for 90 days and were divided into a futile recanalization group and a favorable prognosis group [90-day modified Rankin Scale score of 0–2].

High baseline PLR, NWU, no first-pass reperfusion, and large baseline ischemic core volume were independent predictors of futile recanalization after successful thrombectomy in patients with AIS. Mediation analysis results indicate that PLR may partially mediate the occurrence of futile recanalization through NWU.

Baseline PLR and NWU were independent predictors of futile recanalization, and higher PLR and NWU values were associated with a higher likelihood of futile recanalization. The findings suggest that early cerebral edema reflected by a high NWU value may be a mediator of PLR-affecting prognosis.

Aloe-emodin (AE), a monomer derived from traditional Chinese medicine, has demonstrated remarkable efficacy in the clinical management of cognitive disorders. Ferroptosis (FPT), a specialized form of programmed cell death, plays a critical role in the pathological progression of various cognitive diseases.

This study explored the therapeutic potential of AE in a rat model of Wilson's disease cognitive impairments (WDCI) and examined whether these effects are mediated through the silencing information regulator 1 (SIRT1)-regulated FPT signaling pathway. Employing techniques, such as the Morris water maze (MWM), Hematoxylin & eosin (H&E) staining, Transmission electron microscopy (TEM), Immunofluorescence (IF), assessments of oxidative stress markers, and measurements of FPT-related protein levels, we evaluated the extent of SIRT1-mediated FPT and the therapeutic efficacy of AE.

The findings from the WD copper-loaded rat model experiments revealed that MWM, H&E, TEM, and IF outcomes indicated AE's potential to promote the restoration of learning and memory functions, ameliorate hippocampal neuronal morphological damage, and preserve cell membrane integrity. Results from western blot (WB) and ELISA analyses demonstrated that AE markedly upregulated the expression of SIRT1, nuclear factor erythroid-2-related factor 2 (Nrf2), solute carrier family 7 member 11 (SCL7A11), and glutathione peroxidase 4 (GPX4) proteins while simultaneously reversing the expression of oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD), and reactive oxygen species (ROS). Consequently, we posit that AE may attenuate WD copper-loaded rat model hippocampal neuronal FPT by activating the SIRT1-mediated signaling pathway.

These findings suggested that AE mitigates WD copper-loaded rat model hippocampal neuronal damage through the activation of SIRT1-mediated FPT, thereby presenting a valuable candidate Chinese herbal monomer for the clinical treatment of WDCI.

Increasing evidence of circadian biology may influence the physiopathologic mechanism, progression, and recovery of stroke. However, few data have shown about circadian rhythm on futile recanalization (FR) in patients treated with endovascular treatment (EVT).

From 2017 to 2021, an observational cohort of acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) underwent EVT was conducted. FR was defined as the failure to achieve functional independence in patients at 90 days after EVT, although the occluded vessels reached a recanalization. The effect of circadian rhythm on FR was investigated using the logistic regression model.

Of 783 patients, there were 149 patients who had stroke onset between 23:00-6:59, 318 patients between 7:00-14:59, and 316 patients between 15:00-22:59. Patients suffered from stroke during 15:00-22:59 had shorter OTP (p =0.001) time, shorter OTR (p<0.001) time, higher rate of intravenous thrombolysis (p =0.001) than groups of other time intervals. The rate of FR post-EVT in patients who had a stroke between 15:00-22:59 was significantly higher than in those with stroke onset between 23:00-6:59 (p =0.017). After adjusting for confounding factors, the time of stroke occurring during 15:00-22:59 (adjusted OR [aOR], 1.652; 95%CI, 1.024-2.666, p =0.04) was an independent predictor of FR.

Circadian rhythm can directly or indirectly affect the occurrence, development, and prognosis of AIS. More studies may be needed in the future to validate the results of our study and to explore the potential mechanisms behind the effects of circadian rhythms on FR.