Inversion of neurovascular coupling after subarachnoid hemorrhage in vivo

Balbi, Matilde; Koide, Masayo; Wellman, George C.; Plesnila, Nikolaus

doi:10.1177/0271678x16686595

Cited by 63 publications

(70 citation statements)

References 32 publications

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“…This is consistent with our results showing that PAs isolated from the brains of SAH animals and pressurized ex vivo dilate in response to modest increases in extracellular K + . However, SAH is associated with an inversion of NVC in animal models; that is, instead of causing vasodilation, neuronal activation causes vasoconstriction in these animals, both in brain slices and in vivo . We have proposed that this inversion of NVC is the result of a pathological increase in basal [K + ] o reflecting enhanced K + efflux by astrocytic endfeet, rather than impaired K IR function.…”

Section: Impact Of Small Vessel Pathologies On the Interplay Between supporting

confidence: 91%

“…In both SAH and CADASIL, dysregulation of brain PA reactivity precedes the onset of neurological deficits. Using well‐established rabbit, rat, and mouse models of SAH, and a transgenic mouse model of CADASIL (TgNotch3 R169C ) in which a human NOTCH3 receptor mutation—the molecular cause of CADASIL—is overexpressed, we have discovered that K V channel activity in PA SMCs is abnormal in both pathological conditions . Although abnormal K V activity could conceivably reflect changes in channel gating properties or recruitment of new K V channel family members, our experimental data demonstrated unchanged τ act , V 0.5 , or k in both disease models.…”

Section: Impact Of Pathological Increases (Cadasil) or Decreases (Sahmentioning

confidence: 79%

“…However, evidence indicates impaired NVC in CADASIL and SAH animal models. As K V channel number in PA SMCs is significantly altered in these 2 pathologies, we used computational modeling to investigate the effect of different K V channel densities on SMC membrane potential when [K + ] o is elevated from 3 to 8 mM.…”

Section: Impact Of Small Vessel Pathologies On the Interplay Between mentioning

confidence: 99%

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The yin and yang of K_V channels in cerebral small vessel pathologies

et al. 2018

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Cerebral SVDs encompass a group of genetic and sporadic pathological processes leading to brain lesions, cognitive decline, and stroke. There is no specific treatment for SVDs, which progress silently for years before becoming clinically symptomatic. Here, we examine parallels in the functional defects of PAs in CADASIL, a monogenic form of SVD, and in response to SAH, a common type of hemorrhagic stroke that also targets the brain microvasculature. Both animal models exhibit dysregulation of the voltage‐gated potassium channel, KV1, in arteriolar myocytes, an impairment that compromises responses to vasoactive stimuli and impacts CBF autoregulation and local dilatory responses to neuronal activity (NVC). However, the extent to which this channelopathy‐like defect ultimately contributes to these pathologies is unknown. Combining experimental data with computational modeling, we describe the role of KV1 channels in the regulation of myocyte membrane potential at rest and during the modest increase in extracellular potassium associated with NVC. We conclude that PA resting membrane potential and myogenic tone depend strongly on KV1.2/1.5 channel density, and that reciprocal changes in KV channel density in CADASIL and SAH produce opposite effects on extracellular potassium‐mediated dilation during NVC.

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Section: Impact Of Small Vessel Pathologies On the Interplay Between supporting

confidence: 91%

Section: Impact Of Pathological Increases (Cadasil) or Decreases (Sahmentioning

confidence: 79%

Section: Impact Of Small Vessel Pathologies On the Interplay Between mentioning

confidence: 99%

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The yin and yang of K_V channels in cerebral small vessel pathologies

et al. 2018

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“…Though the exact mechanism of how vasospasm occurs is still not completely elucidated, there are many proposed mechanisms, with cerebral vasospasm likely being a multifactorial pathology. The major proposed pathways contributing to vasospasm include the following: endothelial damage and formation of microthrombi, smooth muscle contraction from lysis of subarachnoid blood clots and blood degradation products and hemoglobin released into the subarachnoid space, decreased nitric oxide production leading to prolonged vasoconstriction, increased production and release of the potent vasoconstrictor endothelin‐1, cortical spreading depolarization, inflammation‐mediated oxidative stress and free radical damage to smooth muscle cells, and upregulation of apoptosis pathways following aSAH (Table ) …”

Section: Resultsmentioning

confidence: 99%

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

et al. 2019

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Aneurysmal subarachnoid hemorrhage (aSAH) continues to be associated with significant morbidity and mortality despite advances in care and aneurysm treatment strategies. Cerebral vasospasm continues to be a major source of clinical worsening in patients. We intended to review the clinical and experimental aspects of aSAH and identify strategies that are being evaluated for the treatment of vasospasm. A literature review on aSAH and cerebral vasospasm was performed. Available treatments for aSAH continue to expand as research continues to identify new therapeutic targets. Oral nimodipine is the primary medication used in practice given its neuroprotective properties. Transluminal balloon angioplasty is widely utilized in patients with symptomatic vasospasm and ischemia. Prophylactic “triple‐H” therapy, clazosentan, and intraarterial papaverine have fallen out of practice. Trials have not shown strong evidence supporting magnesium or statins. Other calcium channel blockers, milrinone, tirilazad, fasudil, cilostazol, albumin, eicosapentaenoic acid, erythropoietin, corticosteroids, minocycline, deferoxamine, intrathecal thrombolytics, need to be further investigated. Many of the current experimental drugs may have significant roles in the treatment algorithm, and further clinical trials are needed. There is growing evidence supporting that early brain injury in aSAH may lead to significant morbidity and mortality, and this needs to be explored further.

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“…The vasoconstriction observed after SAH is thought to be caused by elevated potassium concentrations outside ( [39]. Such an inversion of neurovascular coupling has also been demonstrated in vivo [40,41].…”

Section: Pathophysiology Of Subarachnoid Hemorrhagementioning

confidence: 85%

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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Inversion of neurovascular coupling after subarachnoid hemorrhage in vivo

Cited by 63 publications

References 32 publications

The yin and yang of K_V channels in cerebral small vessel pathologies

The yin and yang of K_V channels in cerebral small vessel pathologies

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

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

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Inversion of neurovascular coupling after subarachnoid hemorrhage in vivo

Cited by 63 publications

References 32 publications

The yin and yang of KV channels in cerebral small vessel pathologies

The yin and yang of KV channels in cerebral small vessel pathologies

Clinical and experimental aspects of aneurysmal subarachnoid hemorrhage

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

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The yin and yang of K_V channels in cerebral small vessel pathologies

The yin and yang of K_V channels in cerebral small vessel pathologies