Current Neurovascular Research - Volume 21, Issue 5, 2024

Early Brain Injury (EBI) significantly contributes to poor neurological outcomes and death following subarachnoid hemorrhage (SAH). The mechanisms underlying EBI post-SAH remain unclear. This study explores the relationship between serial cerebral blood flow (CBF) changes and neurological symptoms, as well as the mechanisms driving CBF changes in the ultra-early stages after experimental SAH in mice.

SAH was induced by endovascular perforation in male ddY mice. Mice were sacrificed at 6, 12, 24, and 48 h after behavioral tests using the modified neurological score and grid walking test, and CBF was measured via Laser Speckle Flow Imaging (LSFI). Neurofunctional evaluation, CBF analysis, and Western blotting were used to assess SAH-induced damage.

Neurological symptoms were significantly worse at 12 h post-SAH compared to sham (9.5 ± 1.7 vs. 25.6 ± 0.63, respectively; p < 0.0001). CBF was significantly reduced at 12 h post-SAH compared to sham (35.34 ± 8.611 vs. 91.06 ± 12.45, respectively; p < 0.0001). Western blotting revealed significantly elevated thrombin and matrix metalloproteinase 9 levels 12 h post-SAH (p < 0.05).

Our results suggest that microthrombus formation peaked at 12 h post-SAH, potentially causing EBI and worsening neurological symptoms. Microthrombus formation in the ultra-early stages may represent a novel therapeutic target for managing EBI.

Bilirubin plays a crucial role in the pathophysiological processes of strokes. However, the relationship between serum bilirubin levels and the prognosis of aneurysmal subarachnoid hemorrhage (aSAH) remains unexplored. This study aims to investigate the association between serum bilirubin levels and the mortality rate of aSAH patients.

695 aSAH patients were included to analyze the relationship between direct bilirubin (DBil), indirect bilirubin (IDBil), total bilirubin (TBil), and mortality. The univariate and multivariate logistic regression were conducted to discover risk factors for the mortality of aSAH. The restricted cubic spline (RCS) was used to show the correlation between DBil, IDBil, TBil, and mortality. A logistic regression predictive model was developed by incorporating significant factors in the multivariate logistic regression. The receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of serum bilirubin and the developed predictive model.

139 aSAH patients suffered death, with a mortality of 20.0%. Non-survivors had older age (p =0.007), lower GCS (p <0.001), higher Hunt Hess (p <0.001), and mFisher (p <0.001). Both DBil (p <0.001) and TBil (p =0.011) were significantly higher among non-survivors. While the IDBil did not show a difference between survivors and non-survivors. The multivariate analysis found age (p =0.111), Glasgow Coma Scale (p =0.005), white blood cell (p <0.001), glucose (p =0.004), DBil (p =0.001), delayed cerebral ischemia (p <0.001) were significantly related with the mortality of aSAH. A logistic regression predictive model for mortality was developed incorporating these five factors, which had an area under the ROC curve (AUC) of 0.876. The AUC of DBil, IDBil, and TBil for predicting mortality was 0.607, 0.570, and 0.529, respectively.

Serum DBil level is positively associated with the mortality risk of aSAH. The predictive model incorporating DBil is beneficial for clinicians to evaluate the mortality risk of aSAH and adopt personalized therapeutics.

Plasma osteoprotegerin (OPG) has been linked to poor prognosis following stroke, but its impact on post-stroke cognitive impairment (PSCI) is unknown. The purpose of our work was to analyze the relationship of OPG with PSCI.

Our study included 613 ischemic stroke subjects with plasma OPG levels. We used the Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to assess PSCI. PSCI was defined as MMSE score <25 or MoCA score <23.

As assessed by the MMSE score, the adjusted odds ratio for PSCI in the highest OPG tertile was 1.77, with a 95% confidence interval of 1.09 to 2.89 (Ptrend=0.021), compared to that in the lowest tertile. We observed a positive linear relationship of plasma OPG levels with 3-month PSCI (P for linearity=0.046). Incorporating plasma OPG into conventional risk factors enhanced PSCI risk reclassification (all P <0.05). Consistent results were discovered when PSCI was evaluated using the MoCA score.

High plasma OPG levels were related to an elevated risk of 3-month PSCI, indicating that OPG might be an effective biomarker for predicting PSCI.

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 concept of “time is brain” is crucial for the reperfusion therapy of ischemic stroke. However, the Infarct Growth Rate (IGR) varies among individuals, which is regarded as a more powerful factor than the time when determining infarct volume and its association with clinical outcomes. For stroke patients with a similar infarct volume, a longer time from stroke Onset to Imaging (OTI) correlates with a lower IGR, which may indicate a better prognosis. This study aimed to compare the prognoses of patients with anterior circulation stroke who received Endovascular Treatment (EVT), specifically comparing early EVT vs. late EVT.

We analyzed 255 patients with acute anterior circulation stroke due to large vessel occlusion and who have successfully undergone recanalization after EVT. All patients were divided into the late (OTI≥6 hours) and early (<6 hours) time window groups and compared. The primary outcome was moderate functional prognosis, defined as a modified Rankin Scale (mRS) ≤3 at 90 days. The secondary outcome was No Significant Infarct Expansion (NSIE), defined as a reduction of less than 2 points on the Alberta Stroke Program Early CT Score (ASPECTS).

In the moderate to large infarct subgroup, the late time window EVT was independently associated with a higher rate of moderate functional outcome (P =0.007) and NSIE (P =0.001); mediation analysis showed that NSIE partially mediated the effects of the late time window EVT on moderate functional outcome (coefficient: 0.112, 95% CI: 0.051 to 0.239, P =0.011); however, these associations were not consistent in the small infarct group.

For anterior circulation stroke patients who received EVT according to current guidelines, those with moderate to large infarct volume and having a longer OTI had better clinical outcomes than those who had a shorter OTI and were more suitable for EVT.

The aim of this study was to explore etiologies and risk factors by age and sex in young adult patients with ischemic stroke.

We recruited patients with ischemic stroke aged between 18 and 49 years. We assessed pathological etiologies by the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification and risk factors by the International Pediatric Stroke Study (IPSS) classification. We explored the distribution of etiologies and risk factors by age and sex and investigated baseline features associated with functional outcomes at 3 months.

Of 8521 stroke patients consecutively admitted, 1017 patients (11.9%) aged between 18-49 years, of whom large artery atherosclerosis was the most common etiology (n=375, 36.9%), followed by other determined cause (n=194, 19.1%) and undetermined cause (n=184, 18.1%). Compared to male patients, female patients had more cardioembolism (16.34% vs 8.42%) and less small artery occlusion (8.56% vs 17.76%). As age increased, the proportions of large artery atherosclerosis (P <0.001) and small artery occlusion (P <0.001) increased, and the proportion of other determined causes decreased (P <0.001). Of 184 patients with undetermined causes, 173 (94.0%) had at least one IPSS risk factor. A higher serum level of D-dimer at baseline was associated with an increased risk of unfavorable outcome (OR 1.118, 95% CI 1.052-1.189), adjusting for the effect of age and stroke severity.

Approximately one-fifth of young patients with ischemic stroke had undetermined etiology, for whom the IPSS classification helps to explore risk factors. A higher level of D-dimer was associated with a higher risk of unfavorable outcomes at 3 months.

Regenerative therapy using stem cells to treat cerebral infarction is currently in the research phase. However, this method is costly. It also faces other significant challenges, including optimization of timing, delivery methods, and dosage. Therefore, more practical and effective therapies are required. Bioabsorbable artificial dura mater made from nonwoven Polyglycolic Acid (PGA) fabric is used clinically to treat cerebral infarction. Basic Fibroblast Growth Factor (bFGF) has attracted considerable attention as a potential therapeutic candidate for the treatment of cerebral infarctions. In this study, we aimed to prepare a bFGF-releasing PGA dura mater and investigate its therapeutic efficacy for the recovery of neurological function in a mouse model of focal cerebral infarction.

An artificial dura mater (Durawave) made from nonwoven PGA fabric was subjected to oxygen plasma treatment, followed by bFGF adsorption. The release of bFGF from the resulting PGA dura mater was evaluated in vitro using enzyme-linked immunosorbent assays. bFGF-releasing PGA dura mater was placed at the site of induced cerebral infarctions in mice. Neurological function was assessed 14 days after insertion, followed by a histological assessment.

The prepared PGA dura mater released bFGF in a dose-dependent manner. Neurological function in the bFGF-treated groups was significantly better than that in the control group. bFGF-releasing PGA dura mater also significantly increased the number of neural progenitor cells in the peri-infarct cortex and striatum and showed a trend toward promoting angiogenesis.

bFGF-releasing PGA dura mater improved neurological function in a mouse model of focal cerebral infarction.

We aimed to investigate the prognostic factors associated with lobar intracerebral hemorrhage (ICH) and to construct convenient models to predict 3-month unfavorable functional outcomes or all-cause death.

Our study included 322 patients with spontaneous lobar ICH from 13 hospitals in Beijing as a derivation cohort. The clinical outcomes were unfavorable functional prognosis, defined as a modified Rankin Scale (mRS) score of 4-6, or all-cause death. Variable selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO) analysis, and two nomogram models were constructed. Additionally, multivariable logistic regression analysis was conducted to identify the factors associated with unfavorable prognosis. Finally, the Area Under The Receiver Operating Characteristic Curve (AUROC), calibration curve, and decision curve analyses (DCA) were performed to evaluate the models in both the derivation and external validation cohorts.

Predictive factors for unfavorable functional outcomes in lobar ICH included age, dyslipidemia, ICH volume, NIHSS score, Stroke-Associated Pneumonia (SAP), and lipid-lowering therapy. The model included age, GCS score, NIHSS score, antihypertensive therapy, in-hospital rehabilitation training, and ICH volume to predict all-cause mortality. Our models exhibited good discriminative ability, with an AUC of 0.897 (95% CI: 0.862-0.933) for unfavorable functional outcomes and 0.894 (95% CI: 0.870-0.918) for death. DCA and calibration curves confirmed the models' excellent clinical decision-making and calibration capabilities.

Nomogram models for predicting 3-month unfavorable outcomes or death in patients with lobar ICH were developed and independently validated in this study, providing valuable prognostic information for clinical decision-making.