Ischemia-induced spreading depolarization in the retina

Srienc, Anja I.; Biesecker, Kyle R.; Shimoda, Angela M.; Kur, Joanna; Newman, Eric A.

doi:10.1177/0271678x16657836

Cited by 15 publications

(16 citation statements)

References 54 publications

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“…Srienc et al tested memantine in rats in which the retinal vessels had been occluded by photothrombosis and observed no significant effect, but there was a trend towards a reduction of incidence. 110 Recently, our group (Santos et al) tested memantine at a dose of 1.5 mg/kg against KCl-induced SD in a gyrencephalic porcine model. An analysis using ECoG and IOS revealed that memantine applied within the therapeutic range had no suppressive effect on SD.…”

Section: Bad Design Of Clinical Trialsmentioning

confidence: 99%

“…Ketamine, a proven blocker of SD, has been shown to stop the neurological aura symptoms in some patients but had no effect on the headache. 120 Many migraine drugs from different pharmacological classes have been tested against SD so far, 50,97,102,110,179,185,[192][193][194][195][196][197][198][199][200][201][202][203][204][205][206][207] and topiramate and flunarizine were most effective since they exerted an inhibitory effect in all of the revised studies.…”

Section: Anti-migraine Drugsmentioning

confidence: 99%

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Systematic review of the pharmacological agents that have been tested against spreading depolarizations

Klass

Sánchez-Porras

Santos

2018

J Cereb Blood Flow Metab

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Spreading depolarization (SD) occurs alongside brain injuries and it can lead to neuronal damage. Therefore, pharmacological modulation of SD can constitute a therapeutic approach to reduce its detrimental effects and to improve the clinical outcome of patients. The major objective of this article was to produce a systematic review of all the drugs that have been tested against SD. Of the substances that have been examined, most have been shown to modulate certain SD characteristics. Only a few have succeeded in significantly inhibiting SD. We present a variety of strategies that have been proposed to overcome the notorious harmfulness and pharmacoresistance of SD. Information on clinically used anesthetic, sedative, hypnotic agents, anti-migraine drugs, anticonvulsants and various other substances have been compiled and reviewed with respect to the efficacy against SD, in order to answer the question of whether a drug at safe doses could be of therapeutic use against SD in humans.

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Section: Bad Design Of Clinical Trialsmentioning

confidence: 99%

Section: Anti-migraine Drugsmentioning

confidence: 99%

Systematic review of the pharmacological agents that have been tested against spreading depolarizations

Klass

Sánchez-Porras

Santos

2018

J Cereb Blood Flow Metab

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“…However, 23 induced one or more BRAO. Of these, 13 used lasers,7–18 five used embolization,19–23 one used heat coagulation by the use of a probe,24 and four used a probe or an occluder 24–27…”

Section: Resultsmentioning

confidence: 99%

“…Six studies used photodynamic therapy or a photodynamic therapy–like method 7–9,11,13,28. In these studies, a photosensitizing agent was administered intravenously or, in one study, intraperitoneally13 followed by application of laser or another light source for a duration varying from 2 to 45 minutes.…”

Section: Resultsmentioning

confidence: 99%

Animal Models Used to Simulate Retinal Artery Occlusion: A Comprehensive Review

Vestergaard

Cehofski

Honoré

et al. 2019

Trans. Vis. Sci. Tech.

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Purpose To present an overview of animal models of retinal artery occlusion (RAO). Methods Through a systematic literature search in PubMed and Embase, papers describing methods of inducing RAO in animal models were included. The identified methodologic approaches were presented in a narrative synthesis and compared with RAO in humans. Results In total, 83 papers reporting on 88 experiments were included. Six different species were used with rodents and monkeys being the most common, and a minority were performed using cats, dogs, rabbits, or pigs. The anatomy of pigs and monkeys resemble that of humans most closely. The two most frequently used methods were laser-induced occlusion or ligation of the arteries. Other methods included raised intraocular pressure, arterial clamping, administration of vasoconstricting agents, the use of an occluder, embolization, and endovascular approaches to induce occlusion. In general, occlusions lasted for only 30 to 90 minutes, often followed by reperfusion. Conclusions Although a broad range of methods have previously been used, they all have limitations. Preferably, the methods should imitate the human disease as closely as possible and avoid damaging other structures. Therefore, monkeys followed by pigs are to be preferred and ligation or clamping may be a suitable model in larger animals as there is a potential to isolate and occlude the retinal artery only. Being less invasive, laser-induced occlusion is another suitable approach. Translational Relevance This review aims at assisting researchers in deciding on the most ideal experimental setting, and thereby increase the translational value to human disease.

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“…The cell type in which Ca v 2.3 should be expressed, was assumed but not proven to be a subtype of amacrine cells. However, it is not excluded that other neurons or even glial cells may harbor the Ca v 2.3/R-type channel.In the vascularized mammalian retina, spreading depolarization can also be demonstrated in vivo [54], which implies that voltage-(and ligand-)gated ion channels are involved in the surface spreading and must be altered in their activity in the retina as well. As the so called "pharmacoresistent" Ca v 2.3/R-type Ca 2+ channel is expressed in the retina [55,56] and was found to be sensitive towards micromolar dihydropyridine concentrations [57,58], the isolated retina should be selected for investigating the molecular mechanisms of electric signaling during early and late stages of SAH, a disease, which is known to be worsened in outcome by a disturbed, maybe even by an inversed neurovascular coupling during which the vessels are constricted instead of being relaxed.…”

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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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Ischemia-induced spreading depolarization in the retina

Cited by 15 publications

References 54 publications

Systematic review of the pharmacological agents that have been tested against spreading depolarizations

Systematic review of the pharmacological agents that have been tested against spreading depolarizations

Animal Models Used to Simulate Retinal Artery Occlusion: A Comprehensive Review

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

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