Imaging of a Clinically Relevant Stroke Model

Arnberg, Fabian; Grafström, Jonas; Lundberg, Johan; Nikkhou-Aski, Sahar; Little, Philip; Damberg, Peter; Mitsios, Nicholas; Mulder, J. W.; Lu, Li; Söderman, Michael; Stone‐Elander, Sharon; Holmin, Staffan

doi:10.1161/strokeaha.114.008407

Cited by 29 publications

(22 citation statements)

References 29 publications

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“…Selective M2 occlusion preserves collateral blood flow to the MCA from the anterior (ACA) and the posterior cerebral arteries (PCA), thereby producing ischemic lesions closer in relative size and with a regional blood flow situation similar to those commonly found in patients [10, 12]. The aim of this study was to use the M2CAO model to provide a clinically relevant profile of the emergence of ischemic injury in such cases.…”

Section: Introductionmentioning

confidence: 99%

Preserved Collateral Blood Flow in the Endovascular M2CAO Model Allows for Clinically Relevant Profiling of Injury Progression in Acute Ischemic Stroke

et al. 2017

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Interventional treatment regimens have increased the demand for accurate understanding of the progression of injury in acute ischemic stroke. However, conventional animal models severely inhibit collateral blood flow and mimic the malignant infarction profile not suitable for treatment. The aim of this study was to provide a clinically relevant profile of the emergence and course of ischemic injury in cases suitable for acute intervention, and was achieved by employing a M2 occlusion model (M2CAO) that more accurately simulates middle cerebral artery (MCA) occlusion in humans. Twenty-five Sprague-Dawley rats were subjected to Short (90 min), Intermediate (180 min) or Extended (600 min) transient M2CAO and examined longitudinally with interleaved diffusion-, T2- and arterial spin labeling perfusion-weighted magnetic resonance imaging before and after reperfusion. We identified a rapid emergence of cytotoxic edema within tissue regions undergoing infarction, progressing in several distinct phases in the form of subsequent moderation and then reversal at 230 min (p < 0.0001). We identified also the early emergence of vasogenic edema, which increased consistently before and after reperfusion (p < 0.0001). The perfusion of the penumbra correlated more strongly to the perfusion of adjacent tissue regions than did the perfusion of regions undergoing infarction (p = 0.0088). This was interpreted as an effect of preserved collateral blood flow during M2CAO. Accordingly, we observed only limited recruitment of penumbra regions to the infarction core. However, a gradual increase in infarction size was still occurring as late as 10 hours after M2CAO. Our results indicate that patients suffering MCA branch occlusion stand to benefit from interventional therapy for an extended time period after the emergence of ischemic injury.

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Section: Introductionmentioning

confidence: 99%

Preserved Collateral Blood Flow in the Endovascular M2CAO Model Allows for Clinically Relevant Profiling of Injury Progression in Acute Ischemic Stroke

et al. 2017

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“…Enhanced gene or protein expression of both GLUT1 and SGLT1 at the BBB has been implicated in experimental models of ischemic stroke and TBI [ 231 , 233 , 234 ]. Consistent with these findings, brain imaging studies have suggested elevated glucose uptake and glucose hypermetabolism during ischemic stroke, especially in peri-infarcted regions [ 234 , 235 ]. Due to the high abundance of GLUTs at the BBB, they are thought to represent a major route for transendothelial water flux during ionic edema, as they have the ability to passively transport water, analogously to the AQPs [ 13 , 14 ].…”

Section: Glucose Transporters (Gluts)mentioning

confidence: 57%

Drug development in targeting ion channels for brain edema

et al. 2020

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Cerebral edema is a pathological hallmark of various central nervous system (CNS) insults, including traumatic brain injury (TBI) and excitotoxic injury such as stroke. Due to the rigidity of the skull, edema-induced increase of intracranial fluid significantly complicates severe CNS injuries by raising intracranial pressure and compromising perfusion. Mortality due to cerebral edema is high. With mortality rates up to 80% in severe cases of stroke, it is the leading cause of death within the first week. Similarly, cerebral edema is devastating for patients of TBI, accounting for up to 50% mortality. Currently, the available treatments for cerebral edema include hypothermia, osmotherapy, and surgery. However, these treatments only address the symptoms and often elicit adverse side effects, potentially in part due to non-specificity. There is an urgent need to identify effective pharmacological treatments for cerebral edema. Currently, ion channels represent the third-largest target class for drug development, but their roles in cerebral edema remain ill-defined. The present review aims to provide an overview of the proposed roles of ion channels and transporters (including aquaporins, SUR1-TRPM4, chloride channels, glucose transporters, and proton-sensitive channels) in mediating cerebral edema in acute ischemic stroke and TBI. We also focus on the pharmacological inhibitors for each target and potential therapeutic strategies that may be further pursued for the treatment of cerebral edema.

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“…Diffusion-weighted magnetic resonance imaging (MRI) has been shown to be an acceptable measure for infarct core volume [19,20] and can be used to ascertain treatment effects. Other advanced imaging modalities such as permeability imaging [21], positron emission tomography [22], thrombus imaging [23], and diffusion tensor imaging [24] can provide critical information on specific intervention targets. Finally, detailed histopathologic analyses can confirm postulated improvements, imaging findings, or safety in animal studies.…”

Section: Going Beyond Functional Endpointsmentioning

confidence: 99%

Academic-industry Collaborations in Translational Stroke Research

Boltze

Wagner

Barthel

et al. 2016

Transl. Stroke Res.

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Academic-industry collaborations are an emerging format of translational stroke research. Next to classic contract research models, a multitude of collaboration models has been developed, some of which even allowing for multinational or intercontinental research programs. This development has recently been paralleled by first successful attempts to overcome the translational stroke research road block, such as the unprecedented success of novel endovascular approaches or the advent of the multicenter preclinical trial concept. While the first underlines the role of the industry as a major innovation driver in stroke research, the latter will require enrollment of industrial partners for optimal output. Moreover, academic-industry partnerships are invaluable to bridge the translational "valley of death" as well as funding gaps in times of dwindling public funding and declining high risk capital investments. However, these collaborations are also subject to relevant challenges because interests, values, and aims often significantly differ between cademia and industry. Here, we describe common academic-industry collaboration models as well as associated benefits and challenges in the stroke research arena. We also suggest strategies for improved planning, implementation, guidance, and utilization of academic-industry collaborations to the maximum mutual benefit.

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Imaging of a Clinically Relevant Stroke Model

Cited by 29 publications

References 29 publications

Preserved Collateral Blood Flow in the Endovascular M2CAO Model Allows for Clinically Relevant Profiling of Injury Progression in Acute Ischemic Stroke

Preserved Collateral Blood Flow in the Endovascular M2CAO Model Allows for Clinically Relevant Profiling of Injury Progression in Acute Ischemic Stroke

Drug development in targeting ion channels for brain edema

Academic-industry Collaborations in Translational Stroke Research

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