Subarachnoid Hemorrhage: a Review of Experimental Studies on the Microcirculation and the Neurovascular Unit

Tso, Michael K; Macdonald, R. Loch

doi:10.1007/s12975-014-0323-4

Cited by 106 publications

(99 citation statements)

References 97 publications

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“…We have not directly demonstrated that etanercept crosses blood-brain barrier; however, etanercept's clear therapeutic effects suggest that the endothelial layer becomes permeable. Indeed, SAH is known to cause substantial blood-brain barrier disruption 39 that permits the diffusion of large proteins. 40 In support of this premise, systemic ( Figure 3E) and intrathecal ( Figure 3G) etanercept have similar effects on the enhanced myogenic tone in SAH: given that smooth muscle cell TNFα augments myogenic tone in SAH ( Figure 2G), it is therefore reasonable to presume that both systemic and intrathecal etanercept sequester smooth muscle cell TNFα.…”

Section: Discussionmentioning

confidence: 99%

Therapeutically Targeting Tumor Necrosis Factor-α/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage

Yagi

Lidington

Wan

et al. 2015

Stroke

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148

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S ubarachnoid hemorrhage (SAH) affects ≈10 in 100 000 people/y.1 Although SAH accounts for only 5% to 10% of all strokes, it is particularly devastating: half of all SAH patients die within 1 month and half of those who survive will require life-long assistance for daily living (ie, ≈75% of patients die or are seriously debilitated).2,3 The poor clinical outcome can be attributed to the biphasic course of the disease, characterized by an initial hemorrhagic stroke that is frequently followed by delayed cerebral ischemia (DCI) within 4 to 12 days. 4,5 The latter is a primary therapeutic concern when treating SAH, because DCI causes at least half of the morbidity and mortality in SAH. 2The transition from the hemorrhagic insult to secondary ischemia is driven by prominent changes in cerebrovascular reactivity, which compromises cerebral autoregulation 6,7 and evokes angiographic vasospasm (ie, radiographically identifiable arterial narrowing in the proximal cerebrovascular circulation).2,8 Conceptually, both events originate from augmentedBackground and Purpose-Subarachnoid hemorrhage (SAH) is a complex stroke subtype characterized by an initial brain injury, followed by delayed cerebrovascular constriction and ischemia. Current therapeutic strategies nonselectively curtail exacerbated cerebrovascular constriction, which necessarily disrupts the essential and protective process of cerebral blood flow autoregulation. This study identifies a smooth muscle cell autocrine/paracrine signaling network that augments myogenic tone in a murine model of experimental SAH: it links tumor necrosis factor-α (TNFα), the cystic fibrosis transmembrane conductance regulator, and sphingosine-1-phosphate signaling. Methods-Mouse olfactory cerebral resistance arteries were isolated, cannulated, and pressurized for in vitro vascular reactivity assessments. Cerebral blood flow was measured by speckle flowmetry and magnetic resonance imaging. Standard Western blot, immunohistochemical techniques, and neurobehavioral assessments were also used. Results-We demonstrate that targeting TNFα and sphingosine-1-phosphate signaling in vivo has potential therapeutic application in SAH. Both interventions (1) eliminate the SAH-induced myogenic tone enhancement, but otherwise leave vascular reactivity intact; (2) ameliorate SAH-induced neuronal degeneration and apoptosis; and (3) improve neurobehavioral performance in mice with SAH. Furthermore, TNFα sequestration with etanercept normalizes cerebral perfusion in SAH. Conclusions-Vascular smooth muscle cell TNFα and sphingosine-1-phosphate signaling significantly enhance cerebral artery tone in SAH; anti-TNFα and anti-sphingosine-1-phosphate treatment may significantly improve clinical outcome.

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Section: Discussionmentioning

confidence: 99%

Therapeutically Targeting Tumor Necrosis Factor-α/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage

Yagi

Lidington

Wan

et al. 2015

Stroke

Self Cite

148

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“…It has been demonstrated that subarachnoid hemorrhage triggers a number of pathophysiological changes in the microvasculature, including a prominent neuroinflammatory response and disruption of the blood-brain barrier. 16 A range of inflammatory mediators are released during subarachnoid hemorrhage, including interleukin (IL)-1b, IL-6, and tumor necrosis factor (TNF)-a, among others, which modulate the cerebral endothelium of the blood-brain barrier, increasing its permeability. 1,7 Experimental studies in animal models have indicated that such inflammatory processes can occur even in regions remote from the bleeding site or the subarachnoid space.…”

Section: Discussionmentioning

confidence: 99%

Enhancing subdural effusions mimicking acute subdural hematomas following angiography and endovascular procedures: report of 2 cases

Zamora

Lin

2015

JNS

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Hyperdense enhancing subdural effusion due to contrast extravasation has been recently described as a potential mimicker of acute subdural hematoma following a percutaneous coronary procedure. Herein, the authors report on 2 patients who presented with subarachnoid hemorrhage from ruptured cerebral aneurysms and who developed enhancing subdural effusions mimicking acute subdural hematomas after angiography and endovascular coil placement. In 1 case, the subdural effusions completely cleared but recurred after a second angiography. CT attenuation values higher than expected for blood, as well as the evolution of the effusions and density over time, allowed for differentiation of enhancing subdural effusions from acute subdural hematomas.

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“…Recent reviews have summarized the present understanding of the pathophysiology of aneurysmal subarachnoid hemorrhage (SAH) quite in detail [34,35]. In most patients, the reason for spontaneous SAH arises from cerebral aneurysm rupture [36].…”

Section: Pathophysiology Of Subarachnoid Hemorrhagementioning

confidence: 99%

“…Much is known about the beneficial effects of dihydropyridine L-type calcium (Ca 2+ ) channel antagonists that are routinely recommended in clinical practice for the prevention and treatment of DCI [34]. When applied in a rather high local concentration, side effects on additional voltage-gated Ca 2+ channels may be assumed, which are rather up-than downregulated in experimentally induced SAH in dogs [42].…”

Section: Voltage-gated Ion Channels Of the Retina May Be Involved In Sahmentioning

confidence: 99%

Selected aspects of retinal signaling and energy metabolism and its perspective as a cerebral surrogate model

Albanna¹,

Lüke²,

Alpdogan³

et al. 2018

New Front Ophthalmol

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Purpose: The isolated and superfused retina from vertebrates is routinely used for neurophysiological measurements of basic retinal signal generation and transduction. Such an ex vivo isolated neural network moreover represents a useful model system for the investigation of drugs and toxins and may also be helpful to elucidate molecular mechanisms of CNS diseases. The present overview aims to bring observations to the reader's attention, which, in part, have been made more than 50 years ago and were sparsely followed up upon in subsequent research, but may support the idea that the isolated bovine retina represents a useful system to investigate the physiology and pathophysiology of energy supply to neuronal tissue. Material and methods:Parallel recording of ERGs and pyridine nucleotide oxidation in the isolated and superfused vertebrate retina. The review will focus on topics, which discuss the connection between retinal electrophysiology and underlying energy metabolism.Results: Previous and present reports about (i) transretinal signaling cascades, (ii) the involvement of the pharmacoresistant Cav2.3 / R-type calcium channel in transretinal signaling and (iii) data about the retinal oxygen demands and concentration in different layers are collected, which elucidate that the retina may be used as a cerebral surrogate model in different research areas. Retinal tolerance to ischemia is several times larger than the tolerance in the remaining brain. Conclusions:The retinal energy supply through retinal vessels is regulated and controlled by neurovascular coupling. Classical retinal recording techniques and special retinal abilities in electrical-vascular coupling will be set in perspective with novel recording techniques, currently brought into clinical application for the detection of impaired neurovascular coupling after aneurysmal subarachnoid hemorrhage in the brain. The present review elucidates that important pathophysiological aspects related to the upregulation of pharmacoresistant Cav2.3 / R-type calcium channels during SAH may be investigated in the isolated vertebrate retina. Ischemic tolerance in the vertebrate retinaThe oxygen consumption of the vertebrate retina on a per gram basis has been described as higher than that of the brain [1,2]. Oxygen cannot be "stored" in tissue so that a constant and adequate supply must be guaranteed to preserve function. Metabolic dysfunction regarding to impaired vascular supply is directly reflected by retinal oxygen saturation which can be detected noninvasively by dual wavelength fundus photography [3]. Normally, the oxygen saturation in retinal vessels differs along vascular segments and is higher in the macular region than retinal periphery [4]. Many retinal diseases are caused by a dysfunction of the vascular network. Interestingly, the venous oxygen saturation in diabetic retinopathy was higher in venules draining the macular surroundings than retinal periphery that reflect specific metabolic conditions [5,6].Since a relatively unobstructed light path...

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Subarachnoid Hemorrhage: a Review of Experimental Studies on the Microcirculation and the Neurovascular Unit

Cited by 106 publications

References 97 publications

Therapeutically Targeting Tumor Necrosis Factor-α/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage

Therapeutically Targeting Tumor Necrosis Factor-α/Sphingosine-1-Phosphate Signaling Corrects Myogenic Reactivity in Subarachnoid Hemorrhage

Enhancing subdural effusions mimicking acute subdural hematomas following angiography and endovascular procedures: report of 2 cases

Selected aspects of retinal signaling and energy metabolism and its perspective as a cerebral surrogate model

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