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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 neuronal and astrocytic interactions in modulating brain endothelial angiogenic potential. A. Effect of metabolically stressed brain endothelial CM (self-conditioned medium) on brain endothelial angiogenesis. Significant increase in number of brain endothelial vessel like structures were observed with self-CM obtained from aglycemic, hypoxic and OGDR treated brain endothelial cells compared to untreated brain endothelial CM. B. Effect of metabolically stressed neuronal CM on brain endothelial angiogenesis. No significant difference in number of vessel like structures were observed with neuronal aglycemic, hypoxic or OGDR CM compared to untreated neuronal CM. C. Effect of metabolically stressed astrocytic CM on brain endothelial angiogenesis. Significant increase in number of vessel like structures were observed with astrocytic aglycemic and OGDR CM compared to untreated astrocyte CM. No significant differences were observed between astrocytic hypoxic CM and untreated astrocytic CM. D. Comparison of untreated CM. A significant increase in vessel like structures were observed with untreated neuronal CM compared to untreated brain endothelial CM. No differences between untreated astrocytic CM and untreated brain endothelial CM was observed. E. Comparison of aglycemic CM. No significant differences were observed between aglycemic brain endothelial, neuronal and astrocytic CM. F. Comparison of hypoxic CM. A significant decrease in vessel like structures were observed with hypoxic neuronal and astrocytic CM compared to hypoxic brain endothelial CM. G. Comparison of OGDR CM from brain endothelial cells, neurons and astrocytes. A significant decrease in vessel like structures were observed with OGDR neuronal and astrocytic CM compared to OGDR brain endothelial CM. One way ANOVA with Bonferroni post testing was used to check significance between 2 specific groups. Un-paired t-test was used to check statistical significance between two groups.*P<0.05 is considered significantly different from controls.
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Figure 2: Differential effects of metabolic stresses on neuronal and astrocytic interactions in modulating brain endothelial angiogenic potential. A. Effect of metabolically stressed brain endothelial CM (self-conditioned medium) on brain endothelial angiogenesis. Significant increase in number of brain endothelial vessel like structures were observed with self-CM obtained from aglycemic, hypoxic and OGDR treated brain endothelial cells compared to untreated brain endothelial CM. B. Effect of metabolically stressed neuronal CM on brain endothelial angiogenesis. No significant difference in number of vessel like structures were observed with neuronal aglycemic, hypoxic or OGDR CM compared to untreated neuronal CM. C. Effect of metabolically stressed astrocytic CM on brain endothelial angiogenesis. Significant increase in number of vessel like structures were observed with astrocytic aglycemic and OGDR CM compared to untreated astrocyte CM. No significant differences were observed between astrocytic hypoxic CM and untreated astrocytic CM. D. Comparison of untreated CM. A significant increase in vessel like structures were observed with untreated neuronal CM compared to untreated brain endothelial CM. No differences between untreated astrocytic CM and untreated brain endothelial CM was observed. E. Comparison of aglycemic CM. No significant differences were observed between aglycemic brain endothelial, neuronal and astrocytic CM. F. Comparison of hypoxic CM. A significant decrease in vessel like structures were observed with hypoxic neuronal and astrocytic CM compared to hypoxic brain endothelial CM. G. Comparison of OGDR CM from brain endothelial cells, neurons and astrocytes. A significant decrease in vessel like structures were observed with OGDR neuronal and astrocytic CM compared to OGDR brain endothelial CM. One way ANOVA with Bonferroni post testing was used to check significance between 2 specific groups. Un-paired t-test was used to check statistical significance between two groups.*P<0.05 is considered significantly different from controls.

Mentions: Conditioned medium from aglycemic, hypoxic and OGDR challenged brain endothelial cells (self conditioned medium from metabolically stressed brain endothelial cells) significantly induced in vitro brain endothelial capillary tube formation on matrigel compared to normal conditioned medium from brain endothelial cells (FigureĀ 2A).


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 neuronal and astrocytic interactions in modulating brain endothelial angiogenic potential. A. Effect of metabolically stressed brain endothelial CM (self-conditioned medium) on brain endothelial angiogenesis. Significant increase in number of brain endothelial vessel like structures were observed with self-CM obtained from aglycemic, hypoxic and OGDR treated brain endothelial cells compared to untreated brain endothelial CM. B. Effect of metabolically stressed neuronal CM on brain endothelial angiogenesis. No significant difference in number of vessel like structures were observed with neuronal aglycemic, hypoxic or OGDR CM compared to untreated neuronal CM. C. Effect of metabolically stressed astrocytic CM on brain endothelial angiogenesis. Significant increase in number of vessel like structures were observed with astrocytic aglycemic and OGDR CM compared to untreated astrocyte CM. No significant differences were observed between astrocytic hypoxic CM and untreated astrocytic CM. D. Comparison of untreated CM. A significant increase in vessel like structures were observed with untreated neuronal CM compared to untreated brain endothelial CM. No differences between untreated astrocytic CM and untreated brain endothelial CM was observed. E. Comparison of aglycemic CM. No significant differences were observed between aglycemic brain endothelial, neuronal and astrocytic CM. F. Comparison of hypoxic CM. A significant decrease in vessel like structures were observed with hypoxic neuronal and astrocytic CM compared to hypoxic brain endothelial CM. G. Comparison of OGDR CM from brain endothelial cells, neurons and astrocytes. A significant decrease in vessel like structures were observed with OGDR neuronal and astrocytic CM compared to OGDR brain endothelial CM. One way ANOVA with Bonferroni post testing was used to check significance between 2 specific groups. Un-paired t-test was used to check statistical significance between two groups.*P<0.05 is considered significantly different from controls.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Differential effects of metabolic stresses on neuronal and astrocytic interactions in modulating brain endothelial angiogenic potential. A. Effect of metabolically stressed brain endothelial CM (self-conditioned medium) on brain endothelial angiogenesis. Significant increase in number of brain endothelial vessel like structures were observed with self-CM obtained from aglycemic, hypoxic and OGDR treated brain endothelial cells compared to untreated brain endothelial CM. B. Effect of metabolically stressed neuronal CM on brain endothelial angiogenesis. No significant difference in number of vessel like structures were observed with neuronal aglycemic, hypoxic or OGDR CM compared to untreated neuronal CM. C. Effect of metabolically stressed astrocytic CM on brain endothelial angiogenesis. Significant increase in number of vessel like structures were observed with astrocytic aglycemic and OGDR CM compared to untreated astrocyte CM. No significant differences were observed between astrocytic hypoxic CM and untreated astrocytic CM. D. Comparison of untreated CM. A significant increase in vessel like structures were observed with untreated neuronal CM compared to untreated brain endothelial CM. No differences between untreated astrocytic CM and untreated brain endothelial CM was observed. E. Comparison of aglycemic CM. No significant differences were observed between aglycemic brain endothelial, neuronal and astrocytic CM. F. Comparison of hypoxic CM. A significant decrease in vessel like structures were observed with hypoxic neuronal and astrocytic CM compared to hypoxic brain endothelial CM. G. Comparison of OGDR CM from brain endothelial cells, neurons and astrocytes. A significant decrease in vessel like structures were observed with OGDR neuronal and astrocytic CM compared to OGDR brain endothelial CM. One way ANOVA with Bonferroni post testing was used to check significance between 2 specific groups. Un-paired t-test was used to check statistical significance between two groups.*P<0.05 is considered significantly different from controls.
Mentions: Conditioned medium from aglycemic, hypoxic and OGDR challenged brain endothelial cells (self conditioned medium from metabolically stressed brain endothelial cells) significantly induced in vitro brain endothelial capillary tube formation on matrigel compared to normal conditioned medium from brain endothelial cells (FigureĀ 2A).

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