Ein Herz für die Schwarzwaldklinik? Zur Persuasionswirkung fiktionaler Fernsehunterhaltung am Beispiel der Organspende-Bereitschaft

Gassmann, Christoph; Vorderer, Peter; Wirth, Werner

doi:10.5771/1615-634x-2003--478

Cited by 2 publications

(1 citation statement)

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“…However, the wide range of HIF targets could have the caveat that modulation of multiple processes could potentially have a negative outcome on whole body physiology. For example, clinical syndromes associated with excessive activation of the HIF pathway exist (Gassmann et al, 2003) and whereas some studies indicate that HIF-1 is neuroprotective, others demonstrate negative outcomes. Clearly, the effects on the NVU in particular must be better understood to ascertain the general widespread application of such therapeutics.…”

Section: Targeted Bbb Cell-specific Treatmentmentioning

confidence: 99%

Cell‐specific blood–brain barrier regulation in health and disease: a focus on hypoxia

Engelhardt

Patkar

Ogunshola

2014

British J Pharmacology

141

125

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The blood-brain barrier (BBB) is a complex vascular structure consisting of microvascular endothelial cells that line the vessel wall, astrocyte end-feet, pericytes, as well as the basal lamina. BBB cells act in concert to maintain the characteristic impermeable and low paracellular flux of the brain vascular network, thus ensuring a homeostatic neuronal environment. Alterations in BBB stability that occur during injury have dire consequences on disease progression and it is clear that BBB cell-specific responses, positive or negative, must make a significant contribution to injury outcome. Reduced oxygenation, or hypoxia, is a characteristic of many brain diseases that significantly increases barrier permeability. Recent data suggest that hypoxia-inducible factor (HIF-1), the master regulator of the hypoxic response, probably mediates many hypoxic effects either directly or indirectly via its target genes. This review discusses current knowledge of physiological cell-specific regulation of barrier function, their responses to hypoxia as well as consequences of hypoxic-and HIF-1-mediated mechanisms on barrier integrity during select brain diseases. In the final sections, the potential of current advances in targeting HIF-1 as a therapeutic strategy will be overviewed. AbbreviationsBBB, blood-brain barrier; HIF-1, hypoxia-inducible factor-1; TJ, tight junction; ECs, endothelial cells; TEER, transendothelial electrical resistanceThe maintenance of CNS homeostasis is performed largely by the blood-brain barrier (BBB), which together with neurons and microglia form an organization referred to as the neurovascular unit (NVU). The BBB is dynamic performing both passive and active features of the brain endothelium essentially acting as a vascular gatekeeper that controls movement of substances from the circulating blood into the brain parenchyma -a role crucial for neuronal, and therefore CNS, homeostasis. Accumulating experimental evidence supports the hypothesis that opening of the BBB triggers a chain of events leading to neuronal dysfunction and damage resulting in neurological disease, and when coupled with previous insults BBB disruption could have serious detrimental consequences for patient outcome. Despite this knowledge, our understanding of physiological barrier function, as well as during disease, is very limited. In addition, the contribution of the perivascular cells that modulate barrier characteristics and their individual responses to injury is poorly characterized. This review will discuss the mechanisms through which hypoxia, a characteristic state of many brain diseases, disrupts barrier function and the importance of BBB cell-specific responses to barrier integrity. Additionally, consequences of hypoxia-mediated barrier modulation during brain disease and future therapeutic use of hypoxia-inducible factor-1 (HIF-1) modulators in the clinics will be reviewed. Physiology BBB organization and cell-specific functionThe BBB is a complex structure consisting of microvascular endothelial cells (ECs) that ...

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Section: Targeted Bbb Cell-specific Treatmentmentioning

confidence: 99%