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Neuronal and astrocytic interactions modulate brain endothelial properties during metabolic stresses of in vitro cerebral ischemia.

Chaitanya GV, Minagar A, Alexander JS - Cell Commun. Signal (2014)

Bottom Line: Neurovascular and gliovascular interactions significantly affect endothelial phenotype.However, in the present study, we used a 3D co-culture model of brain endothelium with neurons and astrocytes in vitro reflecting an intimate neurovascular and gliovascular interactions in vivo.While the cellular signaling interactions in neurovascular and gliovascular units in vivo are much more complex than the 3D co-culture models in vitro, we were still able to observe several important phenotypical changes in brain endothelial properties by metabolically stressed neurons and astrocytes including changes in barrier, lymphocyte adhesive properties, endothelial cell adhesion molecule expression and in vitro angiogenic potential.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health-Shreveport, Louisiana 71103, USA. jalexa@lsuhsc.edu.

ABSTRACT
Neurovascular and gliovascular interactions significantly affect endothelial phenotype. Physiologically, brain endothelium attains several of its properties by its intimate association with neurons and astrocytes. However, during cerebrovascular pathologies such as cerebral ischemia, the uncoupling of neurovascular and gliovascular units can result in several phenotypical changes in brain endothelium. The role of neurovascular and gliovascular uncoupling in modulating brain endothelial properties during cerebral ischemia is not clear. Specifically, the roles of metabolic stresses involved in cerebral ischemia, including aglycemia, hypoxia and combined aglycemia and hypoxia (oxygen glucose deprivation and re-oxygenation, OGDR) in modulating neurovascular and gliovascular interactions are not known. The complex intimate interactions in neurovascular and gliovascular units are highly difficult to recapitulate in vitro. However, in the present study, we used a 3D co-culture model of brain endothelium with neurons and astrocytes in vitro reflecting an intimate neurovascular and gliovascular interactions in vivo. While the cellular signaling interactions in neurovascular and gliovascular units in vivo are much more complex than the 3D co-culture models in vitro, we were still able to observe several important phenotypical changes in brain endothelial properties by metabolically stressed neurons and astrocytes including changes in barrier, lymphocyte adhesive properties, endothelial cell adhesion molecule expression and in vitro angiogenic potential.

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Differential effects of metabolic stresses on brain endothelial, neurovascular and gliovascular-leukocyte adhesive interactions. A. Effect of metabolic stresses on brain endothelial-lymphocyte adhesion. Hypoxic and OGDR treated brain endothelial cells significantly promoted lymphocyte adhesion compared to untreated and aglycemic brain endothelial cells. B. Effect of metabolic stresses on neurovascular-lymphocyte adhesion. Similar to brain endothelial-lymphocyte adhesion, hypoxia and OGDR significantly induced neurovascular-lymphocyte adhesion compared to untreated and aglycemic neurovascular-lymphocyte adhesion. C. Effect of metabolic stresses on gliovascular-lymphocyte adhesion. Similar to brain endothelial and neurovascular-lymphocyte adhesion, hypoxia and OGDR significantly induced gliovascular-lymphocyte adhesion compared to untreated and aglycemic gliovascular-lymphocyte adhesion. D. Comparison of untreated brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in neurovascular and gliovascular-lymphocyte adhesion was observed compared to untreated brain endothelial cells. E. Comparison of aglycemic brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in aglycemic neurovascular and gliovascular-lymphocyte adhesion was observed compared to aglycemic brain endothelial cells. F. Comparison of hypoxic brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. No significant difference in hypoxic neurovascular and gliovascular-lymphocyte adhesion compared to hypoxic brain endothelial cells was observed. G. Comparison of OGDR brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in OGDR neurovascular and gliovascular-lymphocyte adhesion was observed compared to OGDR brain endothelial cells. Un-paired t-test is used to check statistical significance between two groups. *P < 0.05 considered significantly different from controls.
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Figure 3: Differential effects of metabolic stresses on brain endothelial, neurovascular and gliovascular-leukocyte adhesive interactions. A. Effect of metabolic stresses on brain endothelial-lymphocyte adhesion. Hypoxic and OGDR treated brain endothelial cells significantly promoted lymphocyte adhesion compared to untreated and aglycemic brain endothelial cells. B. Effect of metabolic stresses on neurovascular-lymphocyte adhesion. Similar to brain endothelial-lymphocyte adhesion, hypoxia and OGDR significantly induced neurovascular-lymphocyte adhesion compared to untreated and aglycemic neurovascular-lymphocyte adhesion. C. Effect of metabolic stresses on gliovascular-lymphocyte adhesion. Similar to brain endothelial and neurovascular-lymphocyte adhesion, hypoxia and OGDR significantly induced gliovascular-lymphocyte adhesion compared to untreated and aglycemic gliovascular-lymphocyte adhesion. D. Comparison of untreated brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in neurovascular and gliovascular-lymphocyte adhesion was observed compared to untreated brain endothelial cells. E. Comparison of aglycemic brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in aglycemic neurovascular and gliovascular-lymphocyte adhesion was observed compared to aglycemic brain endothelial cells. F. Comparison of hypoxic brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. No significant difference in hypoxic neurovascular and gliovascular-lymphocyte adhesion compared to hypoxic brain endothelial cells was observed. G. Comparison of OGDR brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in OGDR neurovascular and gliovascular-lymphocyte adhesion was observed compared to OGDR brain endothelial cells. Un-paired t-test is used to check statistical significance between two groups. *P < 0.05 considered significantly different from controls.

Mentions: While aglycemia did not affect brain endothelial-lymphocyte adhesive interactions, hypoxia and OGDR challenged brain endothelial cells significantly promoted lymphocyte adhesion in vitro compared to control (nomal) (Figure 3A).


Neuronal and astrocytic interactions modulate brain endothelial properties during metabolic stresses of in vitro cerebral ischemia.

Chaitanya GV, Minagar A, Alexander JS - Cell Commun. Signal (2014)

Differential effects of metabolic stresses on brain endothelial, neurovascular and gliovascular-leukocyte adhesive interactions. A. Effect of metabolic stresses on brain endothelial-lymphocyte adhesion. Hypoxic and OGDR treated brain endothelial cells significantly promoted lymphocyte adhesion compared to untreated and aglycemic brain endothelial cells. B. Effect of metabolic stresses on neurovascular-lymphocyte adhesion. Similar to brain endothelial-lymphocyte adhesion, hypoxia and OGDR significantly induced neurovascular-lymphocyte adhesion compared to untreated and aglycemic neurovascular-lymphocyte adhesion. C. Effect of metabolic stresses on gliovascular-lymphocyte adhesion. Similar to brain endothelial and neurovascular-lymphocyte adhesion, hypoxia and OGDR significantly induced gliovascular-lymphocyte adhesion compared to untreated and aglycemic gliovascular-lymphocyte adhesion. D. Comparison of untreated brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in neurovascular and gliovascular-lymphocyte adhesion was observed compared to untreated brain endothelial cells. E. Comparison of aglycemic brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in aglycemic neurovascular and gliovascular-lymphocyte adhesion was observed compared to aglycemic brain endothelial cells. F. Comparison of hypoxic brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. No significant difference in hypoxic neurovascular and gliovascular-lymphocyte adhesion compared to hypoxic brain endothelial cells was observed. G. Comparison of OGDR brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in OGDR neurovascular and gliovascular-lymphocyte adhesion was observed compared to OGDR brain endothelial cells. Un-paired t-test is used to check statistical significance between two groups. *P < 0.05 considered significantly different from controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3927849&req=5

Figure 3: Differential effects of metabolic stresses on brain endothelial, neurovascular and gliovascular-leukocyte adhesive interactions. A. Effect of metabolic stresses on brain endothelial-lymphocyte adhesion. Hypoxic and OGDR treated brain endothelial cells significantly promoted lymphocyte adhesion compared to untreated and aglycemic brain endothelial cells. B. Effect of metabolic stresses on neurovascular-lymphocyte adhesion. Similar to brain endothelial-lymphocyte adhesion, hypoxia and OGDR significantly induced neurovascular-lymphocyte adhesion compared to untreated and aglycemic neurovascular-lymphocyte adhesion. C. Effect of metabolic stresses on gliovascular-lymphocyte adhesion. Similar to brain endothelial and neurovascular-lymphocyte adhesion, hypoxia and OGDR significantly induced gliovascular-lymphocyte adhesion compared to untreated and aglycemic gliovascular-lymphocyte adhesion. D. Comparison of untreated brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in neurovascular and gliovascular-lymphocyte adhesion was observed compared to untreated brain endothelial cells. E. Comparison of aglycemic brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in aglycemic neurovascular and gliovascular-lymphocyte adhesion was observed compared to aglycemic brain endothelial cells. F. Comparison of hypoxic brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. No significant difference in hypoxic neurovascular and gliovascular-lymphocyte adhesion compared to hypoxic brain endothelial cells was observed. G. Comparison of OGDR brain endothelial, neurovascular and gliovascular-lymphocyte adhesion. A significant increase in OGDR neurovascular and gliovascular-lymphocyte adhesion was observed compared to OGDR brain endothelial cells. Un-paired t-test is used to check statistical significance between two groups. *P < 0.05 considered significantly different from controls.
Mentions: While aglycemia did not affect brain endothelial-lymphocyte adhesive interactions, hypoxia and OGDR challenged brain endothelial cells significantly promoted lymphocyte adhesion in vitro compared to control (nomal) (Figure 3A).

Bottom Line: Neurovascular and gliovascular interactions significantly affect endothelial phenotype.However, in the present study, we used a 3D co-culture model of brain endothelium with neurons and astrocytes in vitro reflecting an intimate neurovascular and gliovascular interactions in vivo.While the cellular signaling interactions in neurovascular and gliovascular units in vivo are much more complex than the 3D co-culture models in vitro, we were still able to observe several important phenotypical changes in brain endothelial properties by metabolically stressed neurons and astrocytes including changes in barrier, lymphocyte adhesive properties, endothelial cell adhesion molecule expression and in vitro angiogenic potential.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health-Shreveport, Louisiana 71103, USA. jalexa@lsuhsc.edu.

ABSTRACT
Neurovascular and gliovascular interactions significantly affect endothelial phenotype. Physiologically, brain endothelium attains several of its properties by its intimate association with neurons and astrocytes. However, during cerebrovascular pathologies such as cerebral ischemia, the uncoupling of neurovascular and gliovascular units can result in several phenotypical changes in brain endothelium. The role of neurovascular and gliovascular uncoupling in modulating brain endothelial properties during cerebral ischemia is not clear. Specifically, the roles of metabolic stresses involved in cerebral ischemia, including aglycemia, hypoxia and combined aglycemia and hypoxia (oxygen glucose deprivation and re-oxygenation, OGDR) in modulating neurovascular and gliovascular interactions are not known. The complex intimate interactions in neurovascular and gliovascular units are highly difficult to recapitulate in vitro. However, in the present study, we used a 3D co-culture model of brain endothelium with neurons and astrocytes in vitro reflecting an intimate neurovascular and gliovascular interactions in vivo. While the cellular signaling interactions in neurovascular and gliovascular units in vivo are much more complex than the 3D co-culture models in vitro, we were still able to observe several important phenotypical changes in brain endothelial properties by metabolically stressed neurons and astrocytes including changes in barrier, lymphocyte adhesive properties, endothelial cell adhesion molecule expression and in vitro angiogenic potential.

Show MeSH
Related in: MedlinePlus