Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro

Zhang, Wandong; Smith, Catherine Delano; Shapiro, Anthony; Monette, Robert; Hutchison, James S.; Stanimirovic, Danica

doi:10.1016/s0165-5728(99)00137-x

Cited by 72 publications

(53 citation statements)

References 49 publications

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“…Increased expression of ICAM-1 by endothelial cells was demonstrated during ischemia/reperfusion, both in vivo and when simulated in vitro (119,456). Oxidative stress preconditioning of cultured endothelial cells reduced their inflammatory response and completely blocked increased ICAM-1 levels induced by TNF-␣ (452); supporting data were obtained with hypoxic preconditioning, which also inhibited the neutrophil adhesion to the endothelial cells induced by hypoxia/reoxygenation (463).…”

Section: Bbb Integritymentioning

confidence: 86%

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Obrenovitch¹

2008

Physiological Reviews

230

176

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Ischemic tolerance describes the adaptive biological response of cells and organs that is initiated by preconditioning (i.e., exposure to stressor of mild severity) and the associated period during which their resistance to ischemia is markedly increased. This topic is attracting much attention because preconditioning-induced ischemic tolerance is an effective experimental probe to understand how the brain protects itself. This review is focused on the molecular and related functional changes that are associated with, and may contribute to, brain ischemic tolerance. When the tolerant brain is subjected to ischemia, the resulting insult severity (i.e., residual blood flow, disruption of cellular transmembrane gradients) appears to be the same as in the naive brain, but the ensuing lesion is substantially reduced. This suggests that the adaptive changes in the tolerant brain may be primarily directed against postischemic and delayed processes that contribute to ischemic damage, but adaptive changes that are beneficial during the subsequent test insult cannot be ruled out. It has become clear that multiple effectors contribute to ischemic tolerance, including: 1) activation of fundamental cellular defense mechanisms such as antioxidant systems, heat shock proteins, and cell death/survival determinants; 2) responses at tissue level, especially reduced inflammatory responsiveness; and 3) a shift of the neuronal excitatory/inhibitory balance toward inhibition. Accordingly, an improved knowledge of preconditioning/ischemic tolerance should help us to identify neuroprotective strategies that are similar in nature to combination therapy, hence potentially capable of suppressing the multiple, parallel pathophysiological events that cause ischemic brain damage.

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Section: Bbb Integritymentioning

confidence: 86%

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Obrenovitch¹

2008

Physiological Reviews

230

176

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“…The hypoxia/reoxygenation-induced transient release of interleukin 1β into the culture medium has been reported previously. Endothelial cells treated with such a medium responded with a pronounced elevation of chemokine expression (Zhang et al, 1999). There are further indications that cerebral ECs cocultured with glial cells are able to cope better with hypoxia.…”

Section: Pathology Of the Bbb-role Of Glia Cellsmentioning

confidence: 93%

In Search of the Astrocytic Factor(s) Modulating Blood–Brain Barrier Functions in Brain Capillary Endothelial Cells In Vitro

2005

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(1) The blood-brain barrier (BBB) is formed by brain capillary endothelial cells (ECs). There are various cell types, in particular astrocytes, but also pericytes and neurons, located in close vicinity to the capillary ECs which may influence formation and function of the BBB. Based on this consideration, this paper discusses various aspects of the influence of the surrounding cells on brain capillary ECs with special focus on the role of astrocytes. (2) Based on the morphology of the BBB, important aspects of brain EC functions are summarized, such as transport functions and maintenance of low paracellular permeability. Moreover, various facets are discussed with respect to the influence of astrocytes, pericytes, microglia, and neurons on the BBB. Data on the role of glial cells in the ontogenesis of the BBB are presented subsequently. The knowledge on this subject is far from being complete, however, these data imply that the neural/neuronal environment rather than glial cells may be of importance in the maturation of the barrier. (3) The role of glial cells in the induction and maintenance of the BBB is discussed under physiological as well as pathological conditions. Although the literature presents manifold evidence for a great variety of effects induced by astroglia, there are also many controversies, which may result from different cellular models and experimental conditions used in the respective studies. Numerous factors secreted by astrocytes have been shown to induce a BBB phenotype. On the molecular level, increased expression of barrier-relevant proteins (e.g., tight junction proteins) is documented in the presence of astrocyte-derived factors, and many studies demonstrate the improvement of physiological parameters, such as increased transendothelial resistance and decreased paracellular permeability, in different in vitro models of the BBB. Moreover, one has to take into account that the interaction of brain ECs and astrocytes is bi-directional, and that the other cell types surrounding the brain microvasculature also contribute to BBB function or dysfunction, respectively. (4) In conclusion, it is expected that the present and future research focused on molecular mechanisms and signaling pathways will produce new and exciting insights into the complex network of BBB regulation: the cornerstone is laid.

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“…MCP-1 is secreted by astrocytes in order to make a chemotactic gradient. Endothelial cells alone or in interaction with invading monocytes could also be a source of MCP-1 (Zhang et al, 1999;Boven et al, 2000;Rimbach et al, 2000). Obviously MCP-1 is present in high concentration during the process of leukocyte transmigration and alteration of tight junction structure and brain endothelial permeability could be very important factor for brain endothelial 'unzipping'.…”

Section: Alteration In Brain Endothelial Permeability By Mcp-1mentioning

confidence: 99%

Potential role of MCP-1 in endothelial cell tight junction `opening': signaling via Rho and Rho kinase

Stamatovic

Keep

Kunkel

et al. 2003

Journal of Cell Science

355

324

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The expression of the monocyte chemoattractant protein-1 (MCP-1) receptor CCR2 by brain endothelial cells suggests that MCP-1 may have other functions than purely driving leukocyte migration into brain parenchyma during inflammation. This study examines one of these potential novel roles of MCP-1 regulation of endothelial permeability using primary cultures of mouse brain endothelial cells. MCP-1 induces reorganization of actin cytoskeleton (stress fiber formation) and redistribution of tight junction proteins, ZO-1, ZO-2 occludin and claudin-5, from the Triton X-100-soluble to the Triton X-100-insoluble fractions. These morphological changes are associated with a decrease in transendothelial electrical membrane resistance and an increase in [14C]inulin permeability. MCP-1 did not induce these events in brain endothelial cells prepared from mice genotype CCR2–/–. The Rho kinase inhibitor Y27632 and inhibition of Rho (C3 exoenzyme, and dominant negative mutant of Rho, RhoT19N) prevented MCP-1-induced stress fiber assembly, reorganization of tight junction proteins and alterations in endothelial permeability. In all, this suggests that a small GTPase Rho and Rho kinase have a pivotal role in MCP-1-induced junction disarrangement. These data are the first to strongly suggest that MCP-1, via CCR2 present on brain endothelial cells, contributes to increased brain endothelial permeability.

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Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro

Cited by 72 publications

References 49 publications

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

In Search of the Astrocytic Factor(s) Modulating Blood–Brain Barrier Functions in Brain Capillary Endothelial Cells In Vitro

Potential role of MCP-1 in endothelial cell tight junction `opening': signaling via Rho and Rho kinase

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