Neurovascular Regulation in the Ischemic Brain

Jackman, Katherine; Iadecola, Costantino

doi:10.1089/ars.2013.5669

Cited by 87 publications

(78 citation statements)

References 83 publications

(78 reference statements)

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“…Vascular networks across cortical layers are heterogeneous (36); thus, this could account for the differences in the vascular responses to chronic cocaine between the superficial and the deep cortical layers. However, the flow redistribution could also reflect differences in neuronal demand needs, vascular innervation, or collateral perfusion between the deep and the superficial cortical layers (37). Alternatively, they could reflect differences in neuronal sensitivity to cocaine, as shown by the higher sensitivity of superficial layers to cocaine's enhancement of sensory signals than that of deep cortical layers (38).…”

Section: Discussionmentioning

confidence: 99%

Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain

et al. 2017

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“…At least for neurovascular coupling after ischemic stroke differences between humans and animals have been described with generally impaired functional hyperemia in animals but variable findings in stroke patients [60]. Another structure playing a key role in the pathophysiology of stroke is the blood-brain barrier (BBB).…”

Section: General Issues Concerning Models Of Ischemic Strokementioning

confidence: 99%

Ischemic stroke: experimental models and reality

2017

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The vast majority of cerebral stroke cases are caused by transient or permanent occlusion of a cerebral blood vessel (“ischemic stroke”) eventually leading to brain infarction. The final infarct size and the neurological outcome depend on a multitude of factors such as the duration and severity of ischemia, the existence of collateral systems and an adequate systemic blood pressure, etiology and localization of the infarct, but also on age, sex, comorbidities with the respective multimedication and genetic background. Thus, ischemic stroke is a highly complex and heterogeneous disorder. It is immediately obvious that experimental models of stroke can cover only individual specific aspects of this multifaceted disease. A basic understanding of the principal molecular pathways induced by ischemia-like conditions comes already from in vitro studies. One of the most frequently used in vivo models in stroke research is the endovascular suture or filament model in rodents with occlusion of the middle cerebral artery (MCA), which causes reproducible infarcts in the MCA territory. It does not require craniectomy and allows reperfusion by withdrawal of the occluding filament. Although promptly restored blood flow is far from the pathophysiology of spontaneous human stroke, it more closely mimics the therapeutic situation of mechanical thrombectomy which is expected to be increasingly applied to stroke patients. Direct transient or permanent occlusion of cerebral arteries represents an alternative approach but requires craniectomy. Application of endothelin-1, a potent vasoconstrictor, allows induction of transient focal ischemia in nearly any brain region and is frequently used to model lacunar stroke. Circumscribed and highly reproducible cortical lesions are characteristic of photothrombotic stroke where infarcts are induced by photoactivation of a systemically given dye through the intact skull. The major shortcoming of this model is near complete lack of a penumbra. The two models mimicking human stroke most closely are various embolic stroke models and spontaneous stroke models. Closeness to reality has its price and goes along with higher variability of infarct size and location as well as unpredictable stroke onset in spontaneous models versus unpredictable reperfusion in embolic clot models.

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“…The brain is endowed with precise control mechanisms that ensure its energy supply well-matched to its energetic needs (Iadecola 2004, 2013; Jackman and Iadecola 2015; Attwell et al 2010; Lauritzen et al 2012). Thus, the functional and structural integrity of the brain relies on a continuous and well-regulated blood supply of oxygen and nutrients, and thus interruption of cerebral blood flow (CBF) results in brain dysfunction and cell death (Iadecola 2004; Lauritzen et al 2012).…”

Section: Role Of Endothelial Cells In Neurovascular Regulationmentioning

confidence: 99%

Endothelial Dysfunction and Amyloid-β-Induced Neurovascular Alterations

2015

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Alzheimer's disease (AD) and cerebrovascular diseases share common vascular risk factors that have disastrous effects on cerebrovascular regulation. Endothelial cells, lining inner walls of cerebral blood vessels, form a dynamic interface between the blood and the brain and are critical for the maintenance of neurovascular homeostasis. Accordingly, injury in endothelial cells is regarded as one of the earliest symptoms of impaired vasoregulatory mechanisms. Extracellular buildup of amyloid-β (Aβ) is a central pathogenic factor in AD. Aβ exerts potent detrimental effects on cerebral blood vessels and impairs endothelial structure and function. Recent evidence implicates vascular oxidative stress and activation of the nonselective cationic channel transient receptor potential melastatin (TRPM)-2 on endothelial cells in the mechanisms of Aβ-induced neurovascular dysfunction. Thus, Aβ triggers opening of TRPM2 channels in endothelial cells leading to intracellular Ca2+ overload and vasomotor dysfunction. The cerebrovascular dysfunction may contribute to AD pathogenesis by reducing the cerebral blood supply, leading to increased susceptibility to vascular insufficiency, and by promoting Aβ accumulation. The recent realization that vascular factors contribute to AD pathobiology suggests new targets for the prevention and treatment of this devastating disease.

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Neurovascular Regulation in the Ischemic Brain

Cited by 87 publications

References 83 publications

Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain

Cerebrovascular adaptations to cocaine-induced transient ischemic attacks in the rodent brain

Ischemic stroke: experimental models and reality

Endothelial Dysfunction and Amyloid-β-Induced Neurovascular Alterations

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