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Development of the blood-brain barrier within the paraventricular nucleus of the hypothalamus: influence of fetal glucocorticoid excess.

Frahm KA, Tobet SA - Brain Struct Funct (2014)

Bottom Line: Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20.In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence.Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

View Article: PubMed Central - PubMed

Affiliation: Program in Cell and Molecular Biology, Colorado State University, 1617 Campus Delivery, Fort Collins, CO, 80523-1617, USA.

ABSTRACT
The blood-brain barrier (BBB) is a critical contributor to brain function. To understand its development and potential function in different brain regions, the postnatal (P) BBB was investigated in the mouse cortex (CTX), lateral hypothalamus, and paraventricular nucleus of the hypothalamus (PVN). Brains were examined on postnatal days (P)12, P22 and P52 for BBB competency and for pericytes as key cellular components of the BBB demarcated by immunoreactive desmin. Glucocorticoid influences (excess dexamethasone; dex) during prenatal development were also assessed for their impact on the blood vessels within these regions postnatally. At P12, there was significantly more extravascular leakage of a low molecular weight dye (fluorescein isothiocyanate) in the CTX than within hypothalamic regions. For pericytes, there were low levels of desmin immunoreactivity at P12 that increased with age for all regions. There was more desmin immunoreactivity present in the PVN at each age examined. Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20. In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence. Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

No MeSH data available.


Related in: MedlinePlus

Postnatal blood–brain barrier development in the mouse cortex (CTX), lateral hypothalamus (LH) and paraventricular nucleus of the hypothalamus (PVN) at P12, P22 and P52. Example confocal images for each region are provided in panels a–i, and a quantitative summary by graph in j. There was a significant increase in extravascular FITC leakage in the CTX (a) compared to the LH (d) and PVN (g) at P12 (j; p < 0.05). Between P12 and P22 there was a significant decrease in extravascular FITC leakage specifically in the CTX (a, b; p < 0.05). At P22, there were no significant differences observed in extravascular FITC leakage between brain regions (b, e, h). At P52, there were no significant differences in extravascular FITC leakage (c, f, i) compared to P22 or between brain regions (j). Number of animals per group (n = 6) is provided in the code for the bars panel j. Significant differences between regions indicated by asterisk and for age as hash. Scale bar 50 µm in panel a, which applies to all images
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Fig1: Postnatal blood–brain barrier development in the mouse cortex (CTX), lateral hypothalamus (LH) and paraventricular nucleus of the hypothalamus (PVN) at P12, P22 and P52. Example confocal images for each region are provided in panels a–i, and a quantitative summary by graph in j. There was a significant increase in extravascular FITC leakage in the CTX (a) compared to the LH (d) and PVN (g) at P12 (j; p < 0.05). Between P12 and P22 there was a significant decrease in extravascular FITC leakage specifically in the CTX (a, b; p < 0.05). At P22, there were no significant differences observed in extravascular FITC leakage between brain regions (b, e, h). At P52, there were no significant differences in extravascular FITC leakage (c, f, i) compared to P22 or between brain regions (j). Number of animals per group (n = 6) is provided in the code for the bars panel j. Significant differences between regions indicated by asterisk and for age as hash. Scale bar 50 µm in panel a, which applies to all images

Mentions: The current study found changes in vasculature structure and extravascular leakage within the CTX, LH and PVN from P12 to P22 and P52. These time points were chosen based on the significant increase in PVN angiogenesis over these ages (Frahm et al. 2012). On P12, the BBB in the CTX was less competent compared to the LH and PVN. There was significant extravascular FITC leakage within the CTX at P12 compared to the LH and PVN (Fig. 1a, d, g, j; p < 0.05). This high level of extravascular FITC was not observed in the hypothalamic regions of LH and PVN at P12. At P22, there was significantly less extravascular FITC leakage in the CTX compared to P12 (Fig. 1b, j; p < 0.05). There were no significant differences between brain regions concerning extravascular FITC leakage at P22 (Fig. 1b, e, h). At P52, the BBB appeared fully functional as extravascular FITC leakage did not change in CTX, LH, and PVN (Fig. 1c, f, i, j) compared to the same brain regions at P22 (Fig. 1b, e, h, j). These findings suggest that the BBB develops at different rates in the CTX compared to the hypothalamic brain regions examined.


Development of the blood-brain barrier within the paraventricular nucleus of the hypothalamus: influence of fetal glucocorticoid excess.

Frahm KA, Tobet SA - Brain Struct Funct (2014)

Postnatal blood–brain barrier development in the mouse cortex (CTX), lateral hypothalamus (LH) and paraventricular nucleus of the hypothalamus (PVN) at P12, P22 and P52. Example confocal images for each region are provided in panels a–i, and a quantitative summary by graph in j. There was a significant increase in extravascular FITC leakage in the CTX (a) compared to the LH (d) and PVN (g) at P12 (j; p < 0.05). Between P12 and P22 there was a significant decrease in extravascular FITC leakage specifically in the CTX (a, b; p < 0.05). At P22, there were no significant differences observed in extravascular FITC leakage between brain regions (b, e, h). At P52, there were no significant differences in extravascular FITC leakage (c, f, i) compared to P22 or between brain regions (j). Number of animals per group (n = 6) is provided in the code for the bars panel j. Significant differences between regions indicated by asterisk and for age as hash. Scale bar 50 µm in panel a, which applies to all images
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4481307&req=5

Fig1: Postnatal blood–brain barrier development in the mouse cortex (CTX), lateral hypothalamus (LH) and paraventricular nucleus of the hypothalamus (PVN) at P12, P22 and P52. Example confocal images for each region are provided in panels a–i, and a quantitative summary by graph in j. There was a significant increase in extravascular FITC leakage in the CTX (a) compared to the LH (d) and PVN (g) at P12 (j; p < 0.05). Between P12 and P22 there was a significant decrease in extravascular FITC leakage specifically in the CTX (a, b; p < 0.05). At P22, there were no significant differences observed in extravascular FITC leakage between brain regions (b, e, h). At P52, there were no significant differences in extravascular FITC leakage (c, f, i) compared to P22 or between brain regions (j). Number of animals per group (n = 6) is provided in the code for the bars panel j. Significant differences between regions indicated by asterisk and for age as hash. Scale bar 50 µm in panel a, which applies to all images
Mentions: The current study found changes in vasculature structure and extravascular leakage within the CTX, LH and PVN from P12 to P22 and P52. These time points were chosen based on the significant increase in PVN angiogenesis over these ages (Frahm et al. 2012). On P12, the BBB in the CTX was less competent compared to the LH and PVN. There was significant extravascular FITC leakage within the CTX at P12 compared to the LH and PVN (Fig. 1a, d, g, j; p < 0.05). This high level of extravascular FITC was not observed in the hypothalamic regions of LH and PVN at P12. At P22, there was significantly less extravascular FITC leakage in the CTX compared to P12 (Fig. 1b, j; p < 0.05). There were no significant differences between brain regions concerning extravascular FITC leakage at P22 (Fig. 1b, e, h). At P52, the BBB appeared fully functional as extravascular FITC leakage did not change in CTX, LH, and PVN (Fig. 1c, f, i, j) compared to the same brain regions at P22 (Fig. 1b, e, h, j). These findings suggest that the BBB develops at different rates in the CTX compared to the hypothalamic brain regions examined.

Bottom Line: Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20.In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence.Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

View Article: PubMed Central - PubMed

Affiliation: Program in Cell and Molecular Biology, Colorado State University, 1617 Campus Delivery, Fort Collins, CO, 80523-1617, USA.

ABSTRACT
The blood-brain barrier (BBB) is a critical contributor to brain function. To understand its development and potential function in different brain regions, the postnatal (P) BBB was investigated in the mouse cortex (CTX), lateral hypothalamus, and paraventricular nucleus of the hypothalamus (PVN). Brains were examined on postnatal days (P)12, P22 and P52 for BBB competency and for pericytes as key cellular components of the BBB demarcated by immunoreactive desmin. Glucocorticoid influences (excess dexamethasone; dex) during prenatal development were also assessed for their impact on the blood vessels within these regions postnatally. At P12, there was significantly more extravascular leakage of a low molecular weight dye (fluorescein isothiocyanate) in the CTX than within hypothalamic regions. For pericytes, there were low levels of desmin immunoreactivity at P12 that increased with age for all regions. There was more desmin immunoreactivity present in the PVN at each age examined. Fetal dex exposure resulted in decreased blood vessel density within the PVN at P20. In the CTX, dex exposure increased BBB competency, in contrast to the PVN where there was a decrease in BBB competency and increased pericyte presence. Overall, unique alterations in the functioning of the BBB within the PVN may provide a novel mechanism for fetal antecedent programming that may influence adult disorders.

No MeSH data available.


Related in: MedlinePlus