Cerebral Collateral Research Articles

Impact of cerebral collateral recycle status on clinical outcomes in elderly patients with endovascular stroke treatment

BackgroundElderly patients are at high risk of acute ischemic stroke caused by large vessel occlusion (AIS-LVO) and usually suffer disability and fatality from stroke even after receiving endovascular treatment (EVT). Previous studies lacked the knowledge of comprehensive cerebral collateral for elderly patients. Hence, we explore the role of cerebral collateral recycle (CCR) status in clinical outcomes in a real-world setting among elderly AIS-LVO patients undergoing EVT. MethodsThis was a multicenter retrospective cohort study. Computed tomographic angiography (CTA) at admission was applied to evaluate cerebral venous outflow profiles by the Cortical Vein Opacification Score (COVES) and pial arterial collaterals by the Tan scale. According to the status of cerebral collaterals, enrolled patients were divided into the poor, moderate, and favorable CCR groups. The primary outcome was functional independence (90-day modified Rankin Scale score 0-2). ResultsAmong 860 AIS-LVO patients receiving EVT, a total of 338 elderly patients were included in the present study after strict screening. Compared with the poor CCR group, the moderate CCR group (31.1% vs. 10.2%; adjusted odds ratio[aOR] 3.80; 95% confidence interval[CI] 1.71-8.44; P=0.001) and the favorable CCR group (63.3% vs. 10.2%; aOR 8.49; 95% CI 4.02-17.92; P<0.001) both had a significantly higher rate of functional independence. In subgroup analysis, similar results were found in AIS-LVO patients with older age, large core infarction, or late time window. ConclusionThe cerebral collateral status in elderly patients with AIS-LVO treated by EVT is a strong predictor of functional outcomes and more robust CCR means better outcomes.

Insights into multilevel tissue-level collateral status using ColorViz maps from dual data sources in acute ischemic cerebrovascular diseases: A STARD-compliant retrospective study.

This study aims to explore the utility of ColorViz mapping from dual data sources for assessing arterial collateral circulation and predicting cerebral tissue-level collateral (TLC) in patients with acute ischemic cerebrovascular diseases. A retrospective study was conducted at a single center on a cohort of 79 patients diagnosed with acute ischemic cerebrovascular diseases between November 2021 and April 2022, who had undergone both multi-phase CT angiography (mCTA) and computed tomography perfusion (CTP). The quality of images and arterial collateral status depicted on ColorViz maps from dual data-sets (mCTA and CTP) were assessed using a "5-point scale" and a "10-point scale," respectively. The status of TLC was evaluated by analyzing multilevel hypoperfusion volume and the hypoperfusion intensity ratio (HIR). The Spearman correlation coefficient was employed to examine the association between arterial collateral status derived from dual data sources and TLC. Receiver operating characteristic curve analysis was used to determine the diagnostic efficacy in detecting large vessel occlusive acute ischemic stroke (LVO-AIS). The ColorViz maps derived from dual data sources facilitated comparable image quality, with over 95% of cases meeting diagnostic criteria, for the evaluation of arterial level collateral circulation. Patients with robust arterial collateral circulation, as determined by dual data sources, were more likely to exhibit favorable TLC status, as evidenced by reductions in hypoperfusion volume (Tmax > 4 seconds, Tmax > 6 seconds, Tmax > 8 seconds, and Tmax > 10 seconds, P < .05) and HIR (Tmax > 6 seconds/4 seconds, Tmax > 8 seconds/4 seconds, Tmax > 10 seconds/4 seconds, and Tmax > 8 seconds/6 seconds, P < .05). The sensitivity and specificity in detecting LVO-AIS was 60.00% and 97.73% for mCTA source maps, while 74.29% and 72.73% for CTP source maps (P > .05 based on De-Long test). In conclusion, this study indicates that ColorViz maps derived from both data sources are equally important in evaluating arterial collateral circulation and enhancing diagnostic efficiency in patients with LVO-AIS, as well as offering insights into the TLC status based on hypoperfusion volume and HIR.

Association between heart failure and cerebral collateral flow in large vessel occlusive ischemic stroke

BackgroundCerebral collateral circulation plays a crucial role in determining the extent of brain ischemia in large vessel occlusive (LVO) stroke. Heart failure (HF) is known to cause cerebral hypoperfusion, yet the relationship between HF and robustness of collateral flow has not been well described. MethodsConsecutive patients with middle cerebral and/or internal carotid LVO who underwent endovascular thrombectomy (EVT) between 2012 and 2020 were included. Single-phase head CTA prior to EVT was used to assess collateral status (poor <50 % filling; good ≥50 %). Classification of HF by left ventricular ejection fraction (LVEF) on echocardiogram was used where HF with reduced ejection fraction (HFrEF) had LVEF ≤40 %, HF with preserved EF (HFpEF) had LVEF ≥50 % with evidence of structural heart disease, and no HF had LVEF≥50 % without structural heart disease. Multivariable logistic regression analyses were performed to evaluate the association between HF and poor collaterals. ResultsWe identified 235 patients, mean age was 69 ± 15 years; initial NIHSS was 18 ± 7. Of these, 107 (45.5 %) had HF and 105 (44.7 %) had poor collaterals. Those with HF were likely to have poor collaterals compared to those without HF (56.1 % vs 35.2 %, P = 0.001). There was a dose-dependent relationship between EF and poor collaterals: adjusted odds of poor collaterals were 1.63 and 2.45 in HFpEF and HFrEF, compared to those without HF (trend P = .018). ConclusionPatients with HFrEF are more likely to have poor cerebral collaterals. Further study is needed to explore the pathomechanisms. Optimization of HF may improve cerebral collaterals and enhance EVT outcomes.

Reconstructive Endovascular Treatment of Compensative-Flow-Related Posterior Circulation Aneurysms With Anterior Circulation Artery Occlusion.

The aim of this study was to delineate the reconstructive endovascular treatment and periprocedural management of compensative-flow-related posterior circulation aneurysms with anterior circulation artery occlusion. A total of 87 patients were enrolled in this retrospective double-center cohort study from May 2011 to November 2023. The baseline demographics, aneurysm characteristics, etiology and status of anterior circulation artery occlusion, treatment modalities, anesthesia management, complications, and clinical and angiographic outcomes of the patients were retrospectively analyzed in this study. Atherosclerosis and moyamoya disease were found to be the two main etiologies of anterior circulation artery occlusion. The mean American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology scores were significantly higher in patients with posterior communicating artery trunk collaterals than those with posterior cerebral artery pial collaterals (P < .05). Treatment strategies included stent-assisted coiling (55, 63.2%), standard coiling (22, 25.3%), and flow diversion or flow diversion-assisted coiling (8, 9.2%). The overall rate of procedure-related ischemic and hemorrhagic complications (10.3%) was considered acceptable. The ischemic complication was significantly associated with a >20% drop in mean arterial pressure (P < .05) during the procedure. Finally, 86.2% of all patients showed a modified Rankin Scale score of 0 to 2 at the final clinical follow-up. Our study indicates that reconstructive endovascular treatments are feasible and effective strategies for compensative-flow-related posterior circulation aneurysms with anterior circulation artery occlusion. However, these treatments are associated with a risk of periprocedural ischemic complications, which can be reduced by collateral arterial assessment, appropriate periprocedural anesthesia management, and antiplatelet treatment.

The clinical and imaging data fusion model for single-period cerebral CTA collateral circulation assessment.

The Chinese population ranks among the highest globally in terms of stroke prevalence. In the clinical diagnostic process, radiologists utilize computed tomography angiography (CTA) images for diagnosis, enabling a precise assessment of collateral circulation in the brains of stroke patients. Recent studies frequently combine imaging and machine learning methods to develop computer-aided diagnostic algorithms. However, in studies concerning collateral circulation assessment, the extracted imaging features are primarily composed of manually designed statistical features, which exhibit significant limitations in their representational capacity. Accurately assessing collateral circulation using image features in brain CTA images still presents challenges. To tackle this issue, considering the scarcity of publicly accessible medical datasets, we combined clinical data with imaging data to establish a dataset named RadiomicsClinicCTA. Moreover, we devised two collateral circulation assessment models to exploit the synergistic potential of patients' clinical information and imaging data for a more accurate assessment of collateral circulation: data-level fusion and feature-level fusion. To remove redundant features from the dataset, we employed Levene's test and T-test methods for feature pre-screening. Subsequently, we performed feature dimensionality reduction using the LASSO and random forest algorithms and trained classification models with various machine learning algorithms on the data-level fusion dataset after feature engineering. Experimental results on the RadiomicsClinicCTA dataset demonstrate that the optimized data-level fusion model achieves an accuracy and AUC value exceeding 86% . Subsequently, we trained and assessed the performance of the feature-level fusion classification model. The results indicate the feature-level fusion classification model outperforms the optimized data-level fusion model. Comparative experiments show that the fused dataset better differentiates between good and bad side branch features relative to the pure radiomics dataset. Our study underscores the efficacy of integrating clinical and imaging data through fusion models, significantly enhancing the accuracy of collateral circulation assessment in stroke patients.

Association of Cerebral Hypoperfusion and Poor Collaterals with Cognitive Impairment in Patients with Severe Vertebrobasilar Artery Stenosis.

Effect of stenosis of vertebrobasilar artery (VBA) on cognitive function is elusive. To investigate association of cerebral hypoperfusion and poor collaterals with vascular cognitive impairment (VCI) in severe VBA stenosis patients. We consecutively enrolled patients with severe VBA stenosis confirmed by digital subtraction angiography who underwent computed tomographic perfusion (CTP) and cognitive assessments. Patients were divided into poor or good collaterals groups according to the collateral circulation status, and were grouped into different perfusion groups according to CTP. Cognitive function was measured by Montreal Cognitive Assessment (MoCA), Clock Drawing Test, Stroop Color Word Test, Trail Making Test, Digital Span Test, Auditory Verbal Learning Test, and Boston Naming Test scales. The association of cerebral perfusion and collaterals with VCI were explored. Among 88 eligible patients, VCI occurred in 51 (57.9%) patients experienced. Poor collateral was present in 73 (83.0%) patients, and hypoperfusion in 64 (72.7%). Compared with normal perfusion patients, the odds ratio with 95% confidence interval for VCI was 12.5 (3.7-42.4) for overall hypoperfusion, 31.0 (7.1-135.5) for multiple site hypoperfusion, 3.3 (1.0-10.5) for poor collaterals, and 0.1 (0-0.6) for presence of posterior communicating artery (PcoA) compensated for posterior cerebral artery (PCA) and basilar artery (BA). Additionally, decreased scores of cognitive function tests occurred in patients with decompensated perfusion or poor collaterals. Hypoperfusion and poor collaterals were positively associated with cognitive impairment in patients with severe VBA. However, PcoA compensated for the PCA and BA had a protective role in cognitive impairment development.

Cerebral collaterals are associated with pre-treatment brain-blood barrier permeability in acute ischemic stroke patients.

To investigate the relationship between collaterals and blood-brain barrier (BBB) permeability on pre-treatment MRI in a cohort of acute ischemic stroke (AIS) patients treated with thrombectomy. We conducted a retrospective analysis of the HIBISCUS-STROKE cohort, a single-center observational study that enrolled patients treated with thrombectomy from 2016 to 2022. Dynamic-susceptibility MRIs were post-processed to generate K2 maps with arrival-time correction, which were co-registered with apparent diffusion coefficient (ADC) maps. The 90th percentile of K2 was extracted from the infarct core-defined by an ADC ≤ 620 × 10-6 mm2/s with manual adjustments-and expressed as a percentage change compared to the contralateral white matter. Collaterals were assessed using pre-thrombectomy digital subtraction arteriography with an ASITN/SIR score < 3 defining poor collaterals. Out of 249 enrolled, 101 (40.6%) were included (median age: 72.0 years, 52.5% of males, median NIHSS score at admission: 15.0). Patients with poor collaterals (n = 44) had worse NIHSS scores (median: 16.0 vs 13.0, p = 0.04), larger infarct core volumes (median: 43.7 mL vs 9.5 mL, p < 0.0001), and higher increases in K2 (median: 346.3% vs 152.7%, p = 0.003). They were less likely to achieve successful recanalization (21/44 vs 51/57, p < 0.0001) and experienced more frequent hemorrhagic transformation (16/44 vs 9/57, p = 0.03). On multiple variable analysis, poor collaterals were associated with larger infarct cores (odds ratio (OR) = 1.12, 95% confidence interval (CI): [1.07, 1.17], p < 0.0001) and higher increases in K2 (OR = 6.63, 95% CI: [2.19, 20.08], p = 0.001). Poor collaterals are associated with larger infarct cores and increased BBB permeability at admission MRI. Poor collaterals are associated with a larger infarct core and increased BBB permeability at admission MRI of AIS patients treated with thrombectomy. These findings may have translational interests for extending thrombolytic treatment eligibility and developing neuroprotective strategies. In AIS, collaterals and BBB disruption have been both linked to hemorrhagic transformation. Poor collaterals were associated with larger ischemic cores and increased BBB permeability on pre-treatment MRI. These findings could contribute to hemorrhagic transformation risk stratification, thereby refining clinical decision-making for reperfusion therapies.

Colour-coded collateral and venous outflow patterns in estimating infarct progression and predicting functional independence for stroke patients in late time window.

To investigate whether cerebral collateral and venous outflow (VO) patterns on colour-coded multi-phase computed tomography angiography (mCTA) can estimate ischaemic core growth rate (IGR) and predict 90-day functional independence for patients with late-presenting acute ischaemic stroke (AIS). The retrospective analysis included 127 AIS patients with a late time window. All patients underwent baseline mCTA with colour-coded reconstruction and computed tomography perfusion. Both collateral score and VO score on colour-coded mCTA maps were analysed and recorded. The IGR was calculated as ischaemic core volume divided by the time from onset to imaging. A 90-day modified Rankin Scale score of 0-2 was defined as functional independence. Kendall's Tau-b analysis was used for nonparametric correlation analysis. Propensity scores, logistic regressions, and receiver operator characteristic (ROC) curves were applied to construct the prediction model. Moderate correlations were found between collateral delay and IGR (Tau-b = -0.554) and between VO and IGR (Tau-b = -0.501). High collateral score (odds ratio = 3.01) and adequate VO (odds ratio = 4.89) remained independent predictors for 90-day functional independence after adjustment. The joint predictive model, which integrated the VO score and clinical features, demonstrated an area under the ROC curve (AUC) of 0.878. The AUCs of collateral score and VO score were 0.836 and 0.883 for outcome prediction after adjustment. Cerebral collateral and VO patterns based on colour-coded mCTA can effectively predict infarct progression and 90-day clinical outcomes, even for AIS patients beyond the routine time window. Colour-coded mCTA is a readily understandable post-processing technique for the rapid assessment of collateral circulation and VO status in stroke imaging. A moderate correlation was observed between the characteristics of collateral delay/VO on colour-coded mCTA and IGR in patients with AIS. Both high-quality collateral circulation and "red superficial middle cerebral vein sign" can predict 90-day functional independence even for patients beyond the routine time window.

Factors associated with venous collaterals in patients with cerebral venous thrombosis.

To identify the factors associated with venous collaterals in Thai patients with cerebral venous thrombosis. This retrospective 20-year cohort study enrolled patients diagnosed with cerebral venous thrombosis between January 2002 and December 2022. Data was collected from the electronic medical record, and venous collaterals were independently reviewed by two neuroradiologists using the Qureshi classification. Patients with and without venous collaterals were compared. Significant factors (P<0.05) in the univariate analysis were recruited into the multivariate logistic regression analysis to determine independently associated factors. Among 79 patients with cerebral venous thrombosis, the prevalence of venous collaterals at the initial neuroimaging was 25.3%. In the univariate analysis, patients with cerebral venous thrombosis and venous collaterals were significantly younger (37.0±13.9 years vs. 44.9±17.4 years, P = 0.048), more often had occlusion in the superior sagittal sinus (80.0% vs. 54.2%, P = 0.041), and were associated with hormonal exposure (35.0% vs. 6.8%, P = 0.002). Multivariate logistic regression analysis revealed occlusion in the superior sagittal sinus (adjusted odds ratio [aOR] 3.581; 95% confidence interval [95% CI] 1.941-13.626; P = 0.044) and hormonal exposure (aOR 7.276, 95% CI 1.606-32.966, P = 0.010) as independent factors associated with venous collaterals in cerebral venous thrombosis. In this cohort, the prevalence of venous collaterals was 25.3%. Occlusion in the superior sagittal sinus and hormonal exposure were independently associated with venous collaterals in patients with cerebral venous thrombosis.

Factors affecting functional independence and recanalization in acute stroke patients undergoing mechanical thrombectomy and the importance of cerebral collateral flow

Factors affecting functional independence and recanalization in acute stroke patients undergoing mechanical thrombectomy and the importance of cerebral collateral flow

An observational and analytical study of clot burden and cerebral collaterals at baseline on functional outcome in patients with acute ischemic stroke

An observational and analytical study of clot burden and cerebral collaterals at baseline on functional outcome in patients with acute ischemic stroke

Stroke mechanisms in adult moyamoya disease: The association between infarction patterns and quantitative magnetic resonance angiography flow state

IntroductionFlow augmentation is the mainstay treatment for moyamoya disease as hemodynamic failure is believed to be the dominant mechanism. We aimed to investigate the mechanisms of stroke in moyamoya disease by assessing the relationship between infarction patterns and quantitative magnetic resonance angiography flow state. MethodsA retrospective study of adult patients with suspected MMD who presented with MRI confirmed acute ischemic stroke predating or following QMRA by a maximum of six months between 2009 and 2021 was conducted. Of the 177 consecutive patients with MMD who received QMRA, 35 patients, consisting of 41 hemispheres, met inclusion criteria. Flow-status was dichotomized into low-flow and normal-flow state based on previously established criteria. ResultsMixed infarction pattern was the most frequent finding (70.7 %), followed by embolic (17.1 %), perforator (7.3 %), and internal borderzone (IBZ) (4.9 %). Infarction patterns were further dichotomized into IBZ+ (internal borderzone alone or mixed) and IBZ− (no internal borderzone constituent). Low-flow states were not significantly more frequent in the IBZ+ compared to IBZ− population (48.4 % vs. 20.0 %, p = 0.14). Ipsilateral posterior cerebral artery fractional flow was significantly higher with IBZ+ compared to IBZ− (345.0 % vs. 214.7 %, p = 0.04). ConclusionMixed infarction pattern was the most common pattern of infarction in patients with moyamoya disease, implying hypoperfusion and thromboembolism are codominant stroke mechanisms. An association between ICA flow status and infarction pattern was not found, although QMRA evidence of more robust posterior cerebral artery leptomeningeal collaterals was found in patients with a hypoperfusion contribution to their stroke mechanism.

Association between left atrial enlargement and poor cerebral collaterals in large vessel occlusion

ObjectivesLeft atrial enlargement (LAE) is a known risk factor for atrial fibrillation, a common cause of large vessel occlusion (LVO) leading to ischemic stroke. While robust cerebral collaterals protect penumbral tissue from infarction, the effect of structural heart disease on cerebral collaterals remains uncertain. This study aims to investigate the association between LAE and cerebral collaterals in patients with acute LVO stroke. Materials and methodsWe conducted a retrospective study of consecutive patients with middle cerebral and/or internal carotid LVO who underwent endovascular thrombectomy (EVT) between 2012 to 2020. Consecutive patients with echocardiography and computed tomography angiography (CTA) of the head were included. Multivariate logistic regression analysis was performed to evaluate the relationship between LAE and poor cerebral collaterals, adjusting for demographics (age, sex, race) and vascular risk factors (hypertension, diabetes and smoking). ResultsThe study included 235 patients with mean age of 69±15 years and an initial mean National Institutes of Health Stroke Scale score of 18. Of these, 89 (37.9 %) had LAE, and 105 (44.7 %) had poor collaterals. Patients with LAE were more likely to have poor collaterals compared to those without LAE (58.4 % vs 36.3 %, P = 0.001). LAE was independently associated with higher odds of poor collaterals (odds ratio, 2.47; P = 0.001), even after adjusting for covariables (odds ratio 1.84, P = 0.048). ConclusionsOur study demonstrated a significant association between LAE and poor cerebral collaterals in patients with LVO stroke undergoing EVT. Further research is warranted to explore potential shared mechanisms, such as endothelial dysfunction, underlying this heart-brain association.

Impact of cerebral collateral flow on stroke outcomes after carotid stenting.

Internal carotid artery stenosis is a main contributor to recurrent ischemic stroke. This study aimed to evaluate associations between recurrent stroke and changes in prestenting flow direction in the primary collaterals or both primary and secondary collaterals, and the potential interaction between extra- and intracranial arteries. This longitudinal study recruited stroke patients without intracranial stenosis who underwent right-side carotid stenting between 2011 and 2019. The main study outcome was recurrent stroke. Predictive factors were anterior circulation flow direction change (ACFDC), posterior circulation flow direction change, and reversal of ophthalmic artery/leptomeningeal anastomosis (ROALA) detected by transcranial color-coded duplex (TCCD) before carotid stenting. Patient follow-up was 9 years. Risk factors for recurrent stroke were identified by Kaplan-Meier plot and Cox regression analyses. A total of 234 patients (mean age 70.88 ± 10.3 years, 86.32% male) were included, and 115 had recurrent stroke. Kaplan-Meier plot showed that patients with left ACFDC and ROALA had worse outcomes than those with ACFDC only, while patients with left ACFDC had worse outcome than those with right ACFDC (both p < 0.001). Cox regression analysis showed that recurrent stoke was associated with ACFDC at right (hazard ratio [95% CI]: 20.988 [2.549-172.790], p < 0.01), left (151.441 [20.100-1140.993], p < 0.001), and both sides (144.889 [19.089-1099.710], p < 0.001). Anterior circulation flow direction change is significantly associated with recurrent stroke in patients with unilateral carotid stenosis. Patients with ACFDC and ROALA together have worse outcomes compared to those with ACFDC only. Prestenting TCCD images help provide definitive information to predict outcomes after carotid stenting.

Large differences in collateral blood vessel abundance among individuals arise from multiple genetic variants

Collateral blood flow varies greatly among humans for reasons that remain unclear, resulting in significant differences in ischemic tissue damage. A similarly large variation has also been found in mice that is caused by genetic background-dependent differences in the extent of collateral formation, termed collaterogenesis—a unique angiogenic process that occurs during development and determines collateral number and diameter in the adult. Previous studies have identified several quantitative trait loci (QTL) linked to this variation. However, understanding has been hampered by the use of closely related inbred strains that do not model the wide genetic variation present in the “outbred” human population. The Collaborative Cross (CC) multiparent mouse genetic reference panel was developed to address this limitation. Herein we measured the number and average diameter of cerebral collaterals in 60 CC strains, their 8 founder strains, 8 F1 crosses of CC strains selected for abundant versus sparse collaterals, and 2 intercross populations created from the latter. Collateral number evidenced 47-fold variation among the 60 CC strains, with 14% having poor, 25% poor-to-intermediate, 47% intermediate-to-good, and 13% good collateral abundance, that was associated with large differences in post-stroke infarct volume. Collateral number in skeletal muscle and intestine of selected high- and low-collateral strains evidenced the same relative abundance as in brain. Genome-wide mapping demonstrated that collateral abundance is a highly polymorphic trait. Subsequent analysis identified: 6 novel QTL circumscribing 28 high-priority candidate genes harboring putative loss-of-function polymorphisms (SNPs) associated with low collateral number; 335 predicted-deleterious SNPs present in their human orthologs; and 32 genes associated with vascular development but lacking protein coding variants. Six additional suggestive QTL (LOD > 4.5) were also identified in CC-wide QTL mapping. This study provides a comprehensive set of candidate genes for future investigations aimed at identifying signaling proteins within the collaterogenesis pathway whose variants potentially underlie genetic-dependent collateral insufficiency in brain and other tissues.

The Critical Role of Equilibrative Nucleoside Transporter-2 in Modulating Cerebral Damage and Vascular Dysfunction in Mice with Brain Ischemia-Reperfusion.

Cerebral vascular protection is critical for stroke treatment. Adenosine modulates vascular flow and exhibits neuroprotective effects, in which brain extracellular concentration of adenosine is dramatically increased during ischemic events and ischemia-reperfusion. Since the equilibrative nucleoside transporter-2 (Ent2) is important in regulating brain adenosine homeostasis, the present study aimed to investigate the role of Ent2 in mice with cerebral ischemia-reperfusion. Cerebral ischemia-reperfusion injury was examined in mice with transient middle cerebral artery occlusion (tMCAO) for 90minutes, followed by 24-hour reperfusion. Infarct volume, brain edema, neuroinflammation, microvascular structure, regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (CMRO2), and the production of reactive oxygen species (ROS) were examined following the reperfusion. Ent2 deletion reduced the infarct volume, brain edema, and neuroinflammation in mice with cerebral ischemia-reperfusion. tMCAO-induced disruption of brain microvessels was ameliorated in Ent2-/- mice, with a reduced expression of matrix metalloproteinases-9 and aquaporin-4 proteins. Following the reperfusion, the rCBF of the wild-type (WT) mice was quickly restored to the baseline, whereas, in Ent2-/- mice, rCBF was slowly recovered initially, but was then higher than that in the WT mice at the later phase of reperfusion. The improved CMRO2 and reduced ROS level support the beneficial effects caused by the changes in the rCBF of Ent2-/- mice. Further studies showed that the protective effects of Ent2 deletion in mice with tMCAO involve adenosine receptor A2AR. Ent2 plays a critical role in modulating cerebral collateral circulation and ameliorating pathological events of brain ischemia and reperfusion injury.

Distinct Alterations in Oxygenation, Ion Composition and Acid-Base Balance in Cerebral Collaterals During Large-Vessel Occlusion Stroke

PurposeDisturbances of blood gas and ion homeostasis including regional hypoxia and massive sodium (Na+)/potassium (K+) shifts are a hallmark of experimental cerebral ischemia but have not been sufficiently investigated for their relevance in stroke patients.MethodsWe report a prospective observational study on 366 stroke patients who underwent endovascular thrombectomy (EVT) for large-vessel occlusion (LVO) of the anterior circulation (18 December 2018–31 August 2020). Intraprocedural blood gas samples (1 ml) from within cerebral collateral arteries (ischemic) and matched systemic control samples were obtained according to a prespecified protocol in 51 patients.ResultsWe observed a significant reduction in cerebral oxygen partial pressure (−4.29%, paO2ischemic = 185.3 mm Hg vs. paO2systemic = 193.6 mm Hg; p = 0.035) and K+ concentrations (−5.49%, K+ischemic = 3.44 mmol/L vs. K+systemic = 3.64 mmol/L; p = 0.0083). The cerebral Na+:K+ ratio was significantly increased and negatively correlated with baseline tissue integrity (r = −0.32, p = 0.031). Correspondingly, cerebral Na+ concentrations were most strongly correlated with infarct progression after recanalization (r = 0.42, p = 0.0033). We found more alkaline cerebral pH values (+0.14%, pHischemic = 7.38 vs. pHsystemic = 7.37; p = 0.0019), with a time-dependent shift towards more acidotic conditions (r = −0.36, p = 0.055).ConclusionThese findings suggest that stroke-induced changes in oxygen supply, ion composition and acid-base balance occur and dynamically progress within penumbral areas during human cerebral ischemia and are related to acute tissue damage.

The impact of collateral status on cerebral vasospasm and delayed cerebral ischemia in subarachnoid hemorrhage.

Cerebral collateral circulation may affect subarachnoid hemorrhage (SAH) induced cerebral vasospasm and delayed cerebral ischemia. In this study our aim was to investigate the relationship between collateral status, vasospasm and delayed cerebral ischemia (DCI) in both aneurysmal and nonaneurysmal SAH. Patients diagnosed as SAH with and without aneurysm were included and their data investigated retrospectively. After the patients diagnosed as SAH according to cerebral computed tomography (CT)/magnetic resonance imaging (MRI), they underwent cerebral angiography to check for cerebral aneurysm. The diagnosis of DCI was made according to the neurological examination and control CT/MRI. All the patients had their control cerebral angiography on days 7 to 10 in order to assess vasospasm and also collateral circulation. The American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) Collateral Flow Grading System was modified to measure collateral circulation. A total of 59 patients data were analyzed. Patients with aneurysmal SAH had higher Fisher scores and DCI was more common. Although there was no statistically significant difference between the patients with and without DCI in terms of demographics and mortality, patients with DCI had worse collateral circulation and more severe vasospasm. These patients had higher Fisher scores and more cerebral aneurysm overall. According to our data, patients with higher Fisher scores, more severe vasospasm, and poor cerebral collateral circulation may experience DCI more frequently. Additionally aneurysmal SAH had higher Fisher scores and DCI was seen more common. To improve the clinical results for SAH patients, we believe that physicians should be aware of the DCI risk factors.

Head Down Tilt 15° in Acute Ischemic Stroke with Poor Collaterals: A Randomized Preclinical Trial

Cerebral collaterals are recruited after arterial occlusion with a protective effect on tissue outcome in acute ischemic stroke. Head down tilt 15° (HDT15) is a simple, low cost and accessible procedure that could be applied as an emergency treatment, before recanalization therapies, with the aim to increase cerebral collateral flow. Spontaneously hypertensive rats have been shown to display anatomical differences in morphology and function of cerebral collaterals, compared to other rat strains, resulting in an overall poor collateral circulation. We investigate the efficacy and safety of HDT15 in spontaneously hypertensive (SHR) rats, which were considered as an animal stroke model with poor collaterals. Cerebral ischemia was induced by 90 minute endovascular occlusion of the middle cerebral artery (MCA). SHR rats were randomized to HDT15 or flat position (n = 19). HDT15 was applied 30 minutes after occlusion and lasted 60 minutes, until reperfusion. HDT15 application increased cerebral perfusion (+16.6% versus +6.1%; p = 0.0040) and resulted in a small reduction of infarct size (83.6 versus 107.1 mm3; − 21.89%; p = 0.0272), but it was not associated with early neurological improvement, compared to flat position. Our study suggests that the response to HDT15 during MCA occlusion is dependent on baseline collaterals. Nonetheless, HDT15 promoted a mild improvement of cerebral hemodynamics even in subjects with poor collaterals, without safety concerns.

Vascular risk factors, cerebral collateral efficiency and burden of small vessel disease in anterior circulation large vessel occlusion stroke (P11-5.025)

<h3>Objective:</h3> To determine the association between cerebral collateral circulation status and cerebral small vessel disease (CSVD) burden. <h3>Background:</h3> Subclinical ischemia is thought to play a central role in CSVD pathogenesis. In patients with large vessel occlusion, good collaterals on initial presentation are associated with improved outcomes. The relationship between an increased burden of CSVD and collateral network has not been explored in the setting of thrombectomy. <h3>Design/Methods:</h3> This was a retrospective single-center cohort of consecutive patients with anterior circulation large vessel occlusions with available brain MRI and CT-Angiogram. We identified the burden of individual CSVD markers[white matter hyperintensities (WMH), cerebral microbleeds(CMB), lacunes, and enlarged perivascular spaces (EPVS)] and computed the global CSVD burden on MRI obtained in the acute stroke. We used the Tan Collateral score (CS) in CT-Angiogram to grade collaterals (0–3; 0=absent supply, 3=100% collateral supply). We performed univariable and multivariable adjusted analyses to explore the association between collaterals and CSVD. <h3>Results:</h3> 237 patients (66.1±16.8 years), 123(52%) female were included. Mean CS was 2(IQR 1–3). WMH (89%), basal ganglia EPVS (77%) and centrum semiovale EPVS (77%) were the most prevalent markers. Older age(beta=0.15, p&lt;0.0001) had the most potent association with individual CSVD markers and higher global CSVD burden. Older age(beta=−0.01, p=0.002) was associated with lower CS. Although a trend was detected between lower CS score and higher WMH burden, it did not reach statistical significance after adjusting for confounders (beta=−0.21, p=0.15). <h3>Conclusions:</h3> In this cohort of large vessel occlusion patients, we found that older age is associated with higher individual CSVD marker and global CSVD burden and poor collateral status. We did not find an overt association between CS and WMH or global CSVD burden. <b>Disclosure:</b> Dr. McMillan has nothing to disclose. Ms. Carvalho has nothing to disclose. Sarah Marchina has nothing to disclose. Dr. Cole has nothing to disclose. Dr. Selim has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MedRhythms Inc.. Dr. Lioutas has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Qmetis. Dr. Lioutas has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Heart Association.