Cerebral collateral circulation in experimental ischemic stroke (original) (raw)
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Collateral Supply in Preclinical Cerebral Stroke Models
Translational Stroke Research
Enhancing the collateral blood supply during the acute phase of cerebral ischemia may limit both the extension of the core infarct, by rescuing the penumbra area, and the degree of disability. Many imaging techniques have been applied to rodents in preclinical studies, to evaluate the magnitude of collateral blood flow and the time course of responses during the early phase of ischemic stroke. The collateral supply follows several different routes at the base of the brain (the circle of Willis) and its surface (leptomeningeal or pial arteries), corresponding to the proximal and distal collateral pathways, respectively. In this review, we describe and illustrate the cerebral collateral systems and their modifications following pre-Willis or post-Willis occlusion in rodents. We also review the potential pharmaceutical agents for stimulating the collateral blood supply tested to date. The time taken to establish a collateral blood flow supply through the leptomeningeal anastomoses diff...
Experimental Neurology, 2012
Intracranial collaterals provide residual blood flow to penumbral tissue in acute ischemic stroke and contribute to infarct size variability in humans. In the present study, hemodynamic monitoring of the borderzone territory between the leptomeningeal branches of middle cerebral artery and anterior cerebral artery was compared to lateral middle cerebral artery territory, during common carotid artery occlusion and middle cerebral artery occlusion in rats. The functional performance of intracranial collaterals, shown by perfusion deficit in the territory of leptomeningeal branches either during common carotid artery occlusion or middle cerebral artery occlusion, showed significant variability among animals and consistently predicted infarct size and functional deficit. Our findings indicate that leptomeningeal collateral flow is a strong predictor of stroke severity in rats, similarly to humans. Monitoring of collateral blood flow in experimental stroke is essential for reducing variability in neuroprotection studies and accelerating the development of collateral therapeutics.
Collateral blood vessels in acute ischemic stroke: a physiological window to predict future outcomes
Arquivos de Neuro-Psiquiatria, 2016
Collateral circulation is a physiologic pathway that protects the brain against ischemic injury and can potentially bypass the effect of a blocked artery, thereby influencing ischemic lesion size and growth. Several recent stroke trials have provided information about the role of collaterals in stroke pathophysiology, and collateral perfusion has been recognized to influence arterial recanalization, reperfusion, hemorrhagic transformation, and neurological outcomes after stroke. Our current aim is to summarize the anatomy and physiology of the collateral circulation and to present and discuss a comprehensible review of the related knowledge, particularly the effects of collateral circulation on the time course of ischemic injury and stroke severity, as well as imaging findings and therapeutic implications.
Journal of Cerebral Blood Flow & Metabolism
Cerebral collaterals are dynamically recruited after arterial occlusion and highly affect tissue outcome in acute ischemic stroke. We investigated the efficacy and safety of four pathophysiologically distinct strategies for acute modulation of collateral flow (collateral therapeutics) in the rat stroke model of transient middle cerebral artery (MCA) occlusion. A composed randomization design was used to assign rats (n = 118) to receive phenylephrine (induced hypertension), polygeline (intravascular volume load), acetazolamide (cerebral arteriolar vasodilation), head down tilt (HDT) 15° (cerebral blood flow diversion), or no treatment, starting 30 min after MCA occlusion. Compared to untreated animals, treatment with collateral therapeutics was associated with lower infarct volumes (62% relative mean difference; 51.57 mm3 absolute mean difference; p
Translational Stroke Research, 2011
In humans and in animal models of stroke, collateral blood flow between territories of the major pial arteries has a profound impact on cortical infarct size. However, there is a gap in our understanding of the genetic determinants of collateral formation and flow, as well as the signaling pathways and neurovascular interactions regulating this flow. Previous studies have demonstrated that collateral flow between branches of the anterior cerebral artery and the middle cerebral artery (MCA) can protect mouse cortex from infarction after MCA occlusion. Because the number and diameter of collaterals vary among mouse strains and after transgenic manipulations, a combination of methods is required to control for these variations. Here, we report an inexpensive approach to characterizing the cerebrovascular anatomy, and in vivo monitoring of cerebral blood flow as well. Further, we introduce a new, minimally invasive method for the occlusion of distal MCA branches. These methods will permit a new generation of studies on the mechanisms regulating collateral remodeling and cortical blood flow after stroke.
The Pathophysiology of Collateral Circulation in Acute Ischemic Stroke
Diagnostics
Cerebral collateral circulation is a network of blood vessels which stabilizes blood flow and maintains cerebral perfusion whenever the main arteries fail to provide an adequate blood supply, as happens in ischemic stroke. These arterial networks are able to divert blood flow to hypoperfused cerebral areas. The extent of the collateral circulation determines the volume of the salvageable tissue, the so-called “penumbra”. Clinically, this is associated with greater efficacy of reperfusion therapies (thrombolysis and thrombectomy) in terms of better short- and long-term functional outcomes, lower incidence of hemorrhagic transformation and of malignant oedema, and smaller cerebral infarctions. Recent advancements in brain imaging techniques (CT and MRI) allow us to study these anastomotic networks in detail and increase the likelihood of making effective therapeutic choices. In this narrative review we will investigate the pathophysiology, the clinical aspects, and the possible diagno...
Collateral blood vessels in acute ischaemic stroke: a potential therapeutic target
The Lancet Neurology, 2011
Ischaemic stroke results from acute arterial occlusion leading to focal hypoperfusion. Thrombolysis is the only proven treatment. Advanced neuroimaging techniques allow a detailed assessment of the cerebral circulation in patients with acute stroke, and provide information about the status of collateral vessels and collateral blood fl ow, which could attenuate the eff ects of arterial occlusion. Imaging of the brain and vessels has shown that collateral fl ow can sustain brain tissue for hours after the occlusion of major arteries to the brain, and the augmentation or maintenance of collateral fl ow is therefore a potential therapeutic target. Several interventions that might augment collateral blood fl ow are being investigated.
Acute development of collateral circulation and therapeutic prospects in ischemic stroke
Neural Regeneration Research, 2016
Acute development of collateral circulation and therapeutic prospects in ischemic stroke The treatment of acute ischemic stroke has entered a new era recently because of the consistent success in endovascular therapy with or without the administration of intravenous recombinant tissue plasminogen activator (IV rtPA). In acute ischemic stroke, tissues that remain alive despite low cerebral blood flow but that are at risk for progressing into infarction are considered to be 'ischemic penumbra.' Both IV rtPA and endovascular therapies can rescue penumbral tissue by recanalizing occluded cerebral arteries. However, even after successful recanalization, some patients show little neurologic improvement, possibly because the penumbral area had already progressed into the irreversibly damaged ischemic core or because hemorrhagic transformation occurred after the recanalization therapy. Collateral circulation has the potential to protect against these ischemic injuries by maintaining cerebral blood flow, and we have focused on collateral circulation in this context. A deterioration in the quality of the collateral circulation
Failure of collateral blood flow is associated with infarct growth in ischemic stroke
Journal of Cerebral Blood Flow & Metabolism, 2013
Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion-diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion-diffusion mismatch (Spearman's Rho 0.51, P < 0.001) and smaller baseline diffusion lesion volu...
The role of leptomeningeal collaterals in redistributing blood flow during stroke
PLOS Computational Biology, 2023
Leptomeningeal collaterals (LMCs) connect the main cerebral arteries and provide alternative pathways for blood flow during ischaemic stroke. This is beneficial for reducing infarct size and reperfusion success after treatment. However, a better understanding of how LMCs affect blood flow distribution is indispensable to improve therapeutic strategies. Here, we present a novel in silico approach that incorporates case-specific in vivo data into a computational model to simulate blood flow in large semi-realistic microvascular networks from two different mouse strains, characterised by having many and almost no LMCs between middle and anterior cerebral artery (MCA, ACA) territories. This framework is unique because our simulations are directly aligned with in vivo data. Moreover, it allows us to analyse perfusion characteristics quantitatively across all vessel types and for networks with no, few and many LMCs. We show that the occlusion of the MCA directly caused a redistribution of blood that was characterised by increased flow in LMCs. Interestingly, the improved perfusion of MCA-sided microvessels after dilating LMCs came at the cost of a reduced blood supply in other brain areas. This effect was enhanced in regions close to the watershed line and when the number of LMCs was increased. Additional dilations of surface and penetrating arteries after stroke improved perfusion across the entire vasculature and partially recovered flow in the obstructed region, especially in networks with many LMCs, which further underlines the role of LMCs during stroke.