Leptomeningeal collateral activation indicates severely impaired cerebrovascular reserve capacity in patients with symptomatic unilateral carotid artery occlusion.
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ABSTRACT:
SUBMITTER: Sebok M
PROVIDER: S-EPMC8545056 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background Comprehensive hemodynamic impairment mapping using blood oxygenation-level dependent (BOLD) cerebrovascular reactivity (CVR) can be used to identify hemodynamically relevant symptomatic unilateral carotid artery disease. Methods and Results This prospective cohort study was conducted between February 2015 and July 2020 at the Clinical Neuroscience Center of the University Hospital Zurich, Zurich, Switzerland. One hundred two patients with newly diagnosed symptomatic unilateral internal carotid artery (ICA) occlusion or with 70% to 99% ICA stenosis were included. An age-matched healthy cohort of 12 subjects underwent an identical BOLD functional magnetic resonance imaging examination. Using BOLD functional magnetic resonance imaging with a standardized CO2 stimulus, CVR impairment was evaluated. Moreover, embolic versus hemodynamic ischemic patterns were evaluated on diffusion-weighted imaging. Sixty-seven patients had unilateral ICA occlusion and 35 patients unilateral 70% to 99% ICA stenosis. Patients with ICA occlusion exhibited lower whole-brain and ipsilateral hemisphere mean BOLD-CVR values as compared with healthy subjects (0.12±0.08 versus 0.19±0.04, P=0.004 and 0.09±0.09 versus 0.18±0.04, P<0.001) and ICA stenosis cohort (0.12±0.08 versus 0.16±0.05, P=0.01 and 0.09±0.09 versus 0.15±0.05, P=0.01); however, only 40 (58%) patients of the cohort showed significant BOLD-CVR impairment. Conversely, there was no difference in mean BOLD-CVR values between healthy patients and patients with ICA stenosis, although 5 (14%) patients with ICA stenosis showed a significant BOLD-CVR impairment. No significant BOLD-CVR difference was discernible between patients with hemodynamic ischemic infarcts versus those with embolic infarct distribution (0.11±0.08 versus 0.13±0.06, P=0.12). Conclusions Comprehensive BOLD-CVR mapping allows for identification of hemodynamically relevant symptomatic unilateral carotid artery stenosis or occlusion.
| S-EPMC8477889 | biostudies-literature
Project description:In patients with carotid artery stenosis (CAS), the risk of stroke, its severity, and response to revascularization are strongly related to the availability of collateral blood flow. Unfortunately, there is poor agreement between observers in assessing collateral flow using flow-based imaging. We used changes in blood-oxygen-level-dependent (BOLD) MRI as a surrogate of changes in regional cerebral blood flow in response to a hypercapnic stimulus [i.e., cerebrovascular reactivity (CVR)] as indicating flow reserve ipsilateral to CAS. We hypothesized that some patients with hemodynamically significant CAS develop functional collateral flow as indicated by normalization of ipsilateral CVR. We identified 55 patients in our CVR database with various degrees of CAS assessed by angiography and classed them as <50% stenosis, 50-69% stenosis, 70-90% stenosis, >90% stenosis, and full occlusion. CVR was measured as the change in BOLD signal in response to changes in end-tidal partial pressure of CO2 (Δ BOLD/Δ PETCO2) and normalized voxel-wise relative to the mean and standard deviation of the CVR in the corresponding voxels of an atlas of 46 healthy controls (CVR z scores). CVR and z scores were then averaged over gray matter (GM) and white matter (WM) on each side of the middle cerebral artery (MCA) territory. As hypothesized, CVR varied for each severity of CAS. Ipsilateral MCA territory CVR was less than normal in each class, including that with <50% stenosis (Student t-test, two-tailed; p = 0.0014 for GM and p = 0.030 for WM), with a trend of decreasing average CVR with increasing stenosis. Remarkably, the considerable individual variability in MCA CVR included some patients with normal CVR in each class - including that with complete occlusion. We conclude that, in general, CAS depresses downstream vascular reserve, but the extent of collateralization is highly variable and not predictable from the degree of stenosis, including both <50% stenosis and complete occlusion. CVR may be the more reliable marker for recruitable collateral blood flow than degree of CAS.
| S-EPMC7528398 | biostudies-literature
Project description:Impairments in cerebrovascular reserve (CVR) have been variably associated with increased risk of ischemic events and may stratify stroke risk in patients with high-grade internal carotid artery stenosis or occlusion. The purpose of this study is to perform a systematic review and meta-analysis to summarize the association of CVR impairment and stroke risk.We performed a literature search evaluating the association of impairments in CVR with future stroke or transient ischemic attack in patients with high-grade internal carotid artery stenosis or occlusion. We included studies with a minimum of 1-year patient follow-up with baseline CVR measures performed by any modality and primary outcome measures of stroke and/or transient ischemic attack. A meta-analysis with assessment of study heterogeneity and publication bias was performed. Results were presented in a forest plot and summarized using a random-effects model.Thirteen studies met the inclusion criteria, representing a total of 1061 independent CVR tests in 991 unique patients with a mean follow-up of 32.7 months. We found a significant positive relationship between impairment of CVR and development of stroke with a pooled random effects OR of 3.86 (95% CI, 1.99-7.48). Subset analysis showed that this association between CVR impairment and future risk of stroke/transient ischemic attack remained significant regardless of ischemic outcome measure, symptomatic or asymptomatic disease, stenosis or occlusion, or CVR testing method.CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion and may be useful for stroke risk stratification.
| S-EPMC3500140 | biostudies-literature
Project description:Background:Chronic iliac vein occlusion can result in the development of a variety of collateral venous drainage pathways. While several drainage pathways have been well documented, autologous sapheno-saphenous bypass collateral drainage has not been described. This novel collateral drainage pathway is readily visible on cross sectional imaging, may serve as a diagnostic indicator of chronic obstructive venous pathology, and may hint at the underlying etiology. Case presentation:This brief report depicts findings and technical considerations in two cases of venous recanalization of sapheno-saphenous collaterals in the setting of chronic unilateral iliac vein occlusion. In both cases at one-month follow-up, the patients' pain had resolved, edema had improved, and computed tomographic venography demonstrated stent patency. Conclusions:Identification of a sapheno-saphenous collateral can provide an important clue to the underlying venous obstructive pathology, therefore guiding corrective intervention.
| S-EPMC6319535 | biostudies-literature
Project description:BackgroundRetinal ischemic stresses are associated with the pathogenesis of various retinal vascular diseases. To investigate pathological mechanisms of retinal ischemia, reproducible, robust and clinically significant experimental rodent models are highly needed. Previously, we established a stable murine model of chronic hypoperfusion retinal injuries by permanent unilateral common carotid artery occlusion (UCCAO) and demonstrated chronic pathological processes in the ischemic retina after the occlusion; however, retinal functional deficits and other acute retinal ischemic injuries by UCCAO still remain obscure. In this study, we attempted to examine retinal functional changes as well as acute retinal ischemic alterations such as retinal thinning, gliosis and cell death after UCCAO.MethodsAdult mice (male C57BL/6, 6-8 weeks old) were subjected to UCCAO in the right side, and retinal function was primarily measured using electroretinography for 14 days after the surgery. Furthermore, retinal thinning, gliosis and cell death were investigated using optical coherence tomography, immunohistochemistry and TUNEL assay, respectively.ResultsFunctional deficits in the unilateral right retina started to be seen 7 days after the occlusion. Specifically, the amplitude of b-wave dramatically decreased while that of a-wave was slightly affected. 14 days after the occlusion, the amplitudes of both waves and oscillatory potentials were significantly detected decreased in the unilateral right retina. Even though a change in retinal thickness was not dramatically observed among all the eyes, retinal gliosis and cell death in the unilateral right retina were substantially observed after UCCAO.ConclusionsAlong with previous retinal ischemic results in this model, UCCAO can stimulate retinal ischemia leading to functional, morphological and molecular changes in the retina. This model can be useful for the investigation of pathological mechanisms for human ischemic retinopathies and furthermore can be utilized to test new drugs for various ischemic ocular diseases.
| S-EPMC8223895 | biostudies-literature
Project description:Cardiovascular diseases lead to retinal ischemia, one of the leading causes of blindness. Retinal ischemia triggers pathological retinal glial responses and functional deficits. Therefore, maintaining retinal neuronal activities and modulating pathological gliosis may prevent loss of vision. Previously, pemafibrate, a selective peroxisome proliferator-activated receptor alpha modulator, was nominated as a promising drug in retinal ischemia. However, a protective role of pemafibrate remains untouched in cardiovascular diseases-mediated retinal ischemia. Therefore, we aimed to unravel systemic and retinal alterations by treating pemafibrate in a new murine model of retinal ischemia caused by cardiovascular diseases. Adult C57BL/6 mice were orally administered pemafibrate (0.5 mg/kg) for 4 days, followed by unilateral common carotid artery occlusion (UCCAO). After UCCAO, pemafibrate was continuously supplied to mice until the end of experiments. Retinal function (a-and b-waves and the oscillatory potentials) was measured using electroretinography on day 5 and 12 after UCCAO. Moreover, the retina, liver, and serum were subjected to qPCR, immunohistochemistry, or ELISA analysis. We found that pemafibrate enhanced liver function, elevated serum levels of fibroblast growth factor 21 (FGF21), one of the neuroprotective molecules in the eye, and protected against UCCAO-induced retinal dysfunction, observed with modulation of retinal gliosis and preservation of oscillatory potentials. Our current data suggest a promising pemafibrate therapy for the suppression of retinal dysfunction in cardiovascular diseases.
| S-EPMC8431531 | biostudies-literature
Project description:Background:Internal carotid artery occlusion (ICAO) is a relatively uncommon but important cause of transient ischemic attack and cerebral infarction. The majority of cases of symptomatic ICAO requires surgical treatment. In this study we performed an investigation of the efficacy and safety of hybrid surgery which is a surgical method for symptomatic chronic complete ICAO. Methods:Fifty-five patients with symptomatic chronic ICAO treated by hybrid surgery from 2016 to 2019 were included. We recorded and analyzed the patients' clinical characteristics, angiographic data, recanalization rate, complications, and outcomes. Catheter angiography or computed tomography angiography was used to assess the patency of the recanalized ICA during follow-up. Results:The total success rate of recanalization was 78.2% (43/55). The occlusions were significantly shorter in the success than failure group (5.40 ± 1.50 vs. 7.56 ± 0.99 cm, respectively; P < 0.001). The median duration of ICA occlusion was significantly shorter in the success than failure group (90 vs. 200 days, respectively). The success rates of distal ICA recanalization at the petrous segment or below, cavernous segment, and clinoid segment or above were 100, 33.3, and 14.3%, respectively (P < 0.001). Multivariate analysis showed that the level of distal ICA reconstitution was the only factor affecting the recanalization success rate. Periprocedural complications included hyperperfusion syndrome (n = 1) and laryngeal nerve injury (n = 1). ICA reocclusion occurred in one patient (2.3%). Significant postoperative improvement in symptoms was observed in the success group, with a median modified Rankin scale score of 0 at the 3-month follow-up compared with before recanalization (median, 1) (P<0.001). Conclusion:Hybrid surgery might be safe and effective for patients with symptomatic chronic complete ICAO. The level of distal ICA reconstitution is a predictor of successful recanalization in hybrid operations.
| S-EPMC7199050 | biostudies-literature
Project description:Carotid artery disease is frequent and can result in chronic modest hypoperfusion of the brain causing cognitive impairments even if classified asymptomatic without a transient ischemic attack or stroke. Paracrine Interleukin 6 (IL 6) improves functional outcome after stroke. However, in carotid artery disease it might have adverse long-term effects. With this exploratory study, we investigated the effect of paracrine IL 6 on cerebral remodeling in early stages after asymptomatic carotid artery occlusion. Therewith we aimed to distinguish IL 6 dependent targets with beneficial effects for long-term outcome from factors causing the detrimental long-term effects of IL 6. To mimic a human asymptomatic carotid artery disease, we used a mouse model of unilateral common carotid artery (CCA) occlusion. We developed a mouse model for inducible paracrine cerebral IL 6 expression (Cx30-Cre-ERT2;FLEX IL6) and induced IL 6 two days after CCA occlusion. We studied the effects of paracrine IL 6 after CCA occlusion on neuronal connectivity using diffusion tensor imaging and on local proteome regulations of the hypo-perfused striatum and contralateral motor cortex using mass spectrometry of laser capture micro-dissected tissues. Paracrine IL-6 induced cerebral remodeling leading to increased inter-hemispheric connectivity and changes in motor system connectivity. We identified changes in local protein abundance which might have adverse effects on functional outcome such as upregulation of Synuclein gamma (Sncg) or downregulation of Proline Dehydrogenase 1 (Prodh). However, we also identified changes in local protein abundance having potentially beneficial effects such as upregulation of Caprin1 or downregulation of GABA transporter 1 (Gat1).
2022-01-27 | PXD029737 | Pride
Project description:Retinal degeneration is a progressive retinal damage in ocular vascular diseases. There are several reasons for this, such as occlusion of arteries or veins, diabetic retinopathy, or hereditary retinal diseases. To study pathological mechanisms of retinal degeneration, it is required to develop experimentally reproducible and clinically relevant models. In our previous studies, we developed a murine model of retinal hypoperfusion by unilateral common carotid artery occlusion (UCCAO) which mimics the pathophysiology of ocular ischemic syndrome (OIS) in humans, and described broad pathological mechanisms in the retina after UCCAO. However, there still remain missing pieces of the ocular pathologic process by UCCAO. In this study, we examined those unfound mechanisms. UCCAO was performed on adult mice. Ocular dysfunctions, histological deficits, and inflammation were examined after UCCAO, compared with sham-operated mice. Evaluation values were analyzed by electrophysiological, histological, and molecular biological methods. Eyelid drooping was permanently seen after UCCAO. Induction time point of acute reversible cataract under anesthesia was shortened. Retinal/visual dysfunctions were detected 2-4 weeks after UCCAO. Specifically, scotopic b-wave was more affected than a-wave, with the dysfunction of photopic b-wave. Impaired oscillatory potentials and visual evoked potential were constantly observed. Pathological Müller gliosis/inflammation was featured with NeuN-positive cell loss in the ganglion cell layer. Axial length, intraocular pressure, pupillary light reflex, and retinal pigment epithelium/choroidal thickness were not changed by UCCAO. A murine model of retinal ischemia by UCCAO can be useful for studying a series of degenerative process in the ischemic retina.
| S-EPMC8741345 | biostudies-literature
Project description:Rigorous screening and good imaging would help perform surgery on carotid artery occlusion CAO safely and effectively. The purpose of this study was to retrospectively evaluate carotid endarterectomy (CEA) recanalization in patients with common carotid artery occlusion (CCAO) or internal carotid artery occlusion (ICAO) with color Doppler flow imaging (CDFI). A total of 59 patients undergoing CEA were enrolled. According to the results of CEA, the patients were divided into successful recanalization (group A) and unsuccessful recanalization (group B) groups. The original diameter, lesion length, proximal-to-distal diameter ratio and echo characteristics of the lesion within the lumen of the carotid artery were recorded before CEA and compared between the two groups. In regards to the achievement of repatency by CEA, the overall success rate was 74.6% (44/59), the success rate in CCAO patients was 75.9% (22/29) and the success rate in ICAO patients was 73.3% (22/30). There was no significant difference in the success rates between the CCAO and ICAO patients (χ2 = 0.050, P = 0.824). The overall rate of stroke and death within 30 postoperative days was 5.1% (3/59). For the CCAO patients, the lesion length in group A was shorter than that in group B (t = 3.221, P = 0.004). For the ICAO patients, the original diameter of the distal ICA was broader (t = 6.254, P = 0.000) and the proximal-to-distal ICA diameter ratio was smaller (t = 8.036, P = 0.000) in group A than in group B. The rate of recanalization for lumens with a homogeneous echo pattern (hypoecho or isoecho) was significantly higher than that for lumens with echo heterogeneity for both the CCAO and ICAO patients (χ2 = 14.477, P = 0.001; χ2 = 10.519, P = 0.003). However, for both the CCAO and ICAO patients, there was no difference in the rate of recanalization between patients with hypoecho and isoecho lesions (χ2 = 0.109, P = 0.742; χ2 = 0.836, P = 0.429). The original diameter, proximal-to-distal ICA diameter ratio, lesion length and echo characteristics may affect the success of CEA recanalization in patients with CCAO and ICAO. CDFI is helpful in screening patients with carotid artery occlusion and may improve the success rate of CEA.
| S-EPMC4670099 | biostudies-literature