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Downstream Microvascular Thrombosis in Cortical Venules Is an Early Response to Proximal Cerebral Arterial Occlusion.

ABSTRACT: BACKGROUND:Previous experimental studies have shown that downstream microvascular thromboinflammation is involved in brain damage from acute ischemic stroke. Using intravital microscopy, we investigated and characterized the sequence of downstream microvascular thromboinflammation in an ischemia/reperfusion acute ischemic stroke model. METHODS AND RESULTS:Rats underwent transient monofilament middle cerebral artery (MCA) occlusion. Cerebral microcirculation in the MCA territory was exposed through a craniotomy and analyzed using real-time intravital imaging coupled with laser Doppler interferometry. Leukocytes, platelets, fibrinogen, and blood-brain barrier permeability were analyzed by intravenous injection of fluorescent antibodies and bovine serum albumin. MCA occlusion induced a sudden and profound drop in downstream microvascular blood flow associated with leukocyte margination in the venous compartment. Leukocyte margination fostered fibrinogen deposition and thrombosis in postcapillary venules. Either in venules or arterioles, blood flow was not fully restored after MCA recanalization. Furthermore, venular thrombi persisted despite MCA recanalization, and leukocyte extravasation continued to develop in venules in association with blood-brain barrier disruption. Finally, microhemorrhages were occasionally observed, colocalizing with thrombosed venules characterized by marked leukocyte margination. CONCLUSIONS:We showed that microvascular thrombosis in transient monofilament MCA occlusion and blood-brain barrier disruption are initiated immediately after occlusion and are propagated through the venous compartment in close association with marginating leukocytes. MCA occlusion-induced downstream microvascular thromboinflammation response was responsible for incomplete reperfusion after MCA recanalization and delayed microhemorrhages.

SUBMITTER: Desilles JP

PROVIDER: S-EPMC5866327 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Downstream Microvascular Thrombosis in Cortical Venules Is an Early Response to Proximal Cerebral Arterial Occlusion.

Desilles Jean-Philippe JP Syvannarath Varouna V Di Meglio Lucas L Ducroux Célina C Boisseau William W Louedec Liliane L Jandrot-Perrus Martine M Michel Jean-Baptiste JB Mazighi Mikael M Ho-Tin-Noé Benoît B

Journal of the American Heart Association 20180301 5

<h4>Background</h4>Previous experimental studies have shown that downstream microvascular thromboinflammation is involved in brain damage from acute ischemic stroke. Using intravital microscopy, we investigated and characterized the sequence of downstream microvascular thromboinflammation in an ischemia/reperfusion acute ischemic stroke model.<h4>Methods and results</h4>Rats underwent transient monofilament middle cerebral artery (MCA) occlusion. Cerebral microcirculation in the MCA territory wa ...[more]

PMID: 29496683

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Project description:Background and purposeProximal middle cerebral artery (MCA) occlusions impede blood flow to the noncollateralized lenticulostriate artery territory. Previous work has shown that this almost inevitably leads to infarction of the dependent gray matter territories in the striate even if perfusion is restored by mechanical thrombectomy. Purpose of this analysis was to evaluate potential sparing of neighboring fiber tracts, ie, the internal capsule.MethodsAn observational single-center study of patients with proximal MCA occlusions treated with mechanical thrombectomy and receiving postinterventional high-resolution diffusion-weighted imaging was conducted. Patients were classified according to internal capsule ischemia (IC+ versus IC-) at the postero-superior level of the MCA lenticulostriate artery territory (corticospinal tract correlate). Associations of IC+ versus IC- with baseline variables as well as its clinical impact were evaluated using multivariable logistic or linear regression analyses adjusting for potential confounders.ResultsOf 92 included patients with proximal MCA territory infarctions, 45 (48.9%) had an IC+ pattern. Longer time from symptom-onset to groin-puncture (adjusted odds ratio, 2.12 [95% CI, 1.19-3.76] per hour), female sex and more severe strokes were associated with IC+. Patients with IC+ had lower rates of substantial neurological improvement and functional independence (adjusted odds ratio, 0.26 [95% CI, 0.09-0.81] and adjusted odds ratio, 0.25 [95% CI, 0.07-0.86]) after adjustment for confounders. These associations remained unchanged when confining analyses to patients without ischemia in the corona radiata or the motor cortex and here, IC+ was associated with higher National Institutes of Health Stroke Scale motor item scores (β, +2.8 [95% CI, 1.5 to 4.1]) without a significant increase in nonmotor items (β, +0.8 [95% CI, -0.2 to 1.9).ConclusionsRapid mechanical thrombectomy with successful reperfusion of the lenticulostriate arteries often protects the internal capsule from subsequent ischemia despite early basal ganglia damage. Salvage of this eloquent white matter tract within the MCA lenticulostriate artery territory seems strongly time-dependent, which has clinical and pathophysiological implications.

Project description:Introduction: Endovascular therapy (EVT) is established as first-line treatment for acute ischemic stroke (AIS) due to large vessel occlusion (LVO) in the anterior circulation. For basilar artery occlusion, recent randomized clinical trials demonstrated not only equipoise but also advantages for EVT under particular circumstances. It remains unclear whether EVT offers an advantage over best medical management (BMM) including thrombolysis (IVT) in isolated occlusion of the proximal posterior cerebral artery (PCAO). Methods: Patients with AIS due to PCAO proven by CT or MR angiography were retrospectively identified from local databases at four comprehensive stroke centers in Germany, USA, and Taiwan between 2012 and 2020. Demographic and clinical data were collected, and imaging characteristics including pretherapeutic, interventional, and follow-up imaging were reviewed locally at each center. Patients were grouped according to therapy, i.e., BMM including IVT alone vs. BMM and EVT. Efficacy endpoints were early neurological improvement (ENI) after 24 h or at discharge, good outcome (modified Rankin scale 0-2) after 3 months, as well as hemorrhagic complications and in-house deaths as safety endpoints. Results: We included 130 patients of whom 23 (17.7%) received EVT. EVT patients had more proximal occlusions (69.9 vs. 43%, p = 0.023) and had a better premorbid function [premorbid mRS, 0 (0-4) vs. 1 (0-3), p < 0.01] when compared to BMM patients. IVT showed a trend toward being less performed in the EVT group (21.7 vs. 41.1%, p = 0.1), while other baseline parameters were balanced. Successful reperfusion was achieved in 52% of EVT patients. ENI was more frequent in the EVT group (61 vs. 35.5%, p = 0.034). Good outcome at 90 days and safety endpoints did not differ. In a bivariate analysis, ENI was independently predicted by the use of EVT (OR, 2.76; CI, 1.055-7.04) and the baseline National Institutes of Health Stroke Scale (NIHSS) (OR, 1.082; CI, 1.027-1.141 per point increase). Discussion: EVT in isolated PCAO appears safe and feasible. Positive effects on clinical outcome are primarily on ENI but also depend on the initial stroke severity. Further prospective or randomized studies are needed to better describe the potential long-term clinical benefits of EVT for PCAO as compared with best medical management.

Dataset Information

Downstream Microvascular Thrombosis in Cortical Venules Is an Early Response to Proximal Cerebral Arterial Occlusion.

Publications

Downstream Microvascular Thrombosis in Cortical Venules Is an Early Response to Proximal Cerebral Arterial Occlusion.

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