Limits...
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

Prenatal exposure to dexamethasone (dex) impacted blood vessel density in the postnatal mouse paraventricular nucleus of the hypothalamus (PVN) at P20. There was a significant decrease in blood vessel length for the entire PVN for dex-treated compared to vehicle-treated mice (a, **p < 0.01). There was also a region-specific significant decrease in blood vessel length in the rostral, mid and caudal regions of the PVN in dex-treated compared to vehicle-treated mice (b, ***p < 0.0001). For branch points, there was only a significant decrease in the rostral and mid PVN in dex-treated compared to vehicle-treated mice (c, *p < 0.05). Number of animals per group (n = 8) is provided in the code for the bars in each panel
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4481307&req=5

Fig4: Prenatal exposure to dexamethasone (dex) impacted blood vessel density in the postnatal mouse paraventricular nucleus of the hypothalamus (PVN) at P20. There was a significant decrease in blood vessel length for the entire PVN for dex-treated compared to vehicle-treated mice (a, **p < 0.01). There was also a region-specific significant decrease in blood vessel length in the rostral, mid and caudal regions of the PVN in dex-treated compared to vehicle-treated mice (b, ***p < 0.0001). For branch points, there was only a significant decrease in the rostral and mid PVN in dex-treated compared to vehicle-treated mice (c, *p < 0.05). Number of animals per group (n = 8) is provided in the code for the bars in each panel

Mentions: Blood vessels that are potentially newly formed and not yet fully functional are not identified by vascular perfusion with FITC (Frahm et al. 2013). Therefore, immunoreactive PECAM was utilized to visualize the more complete endothelial cell population. PECAM revealed an overall 13 % decrease in blood vessel length in the PVN for dex-treated compared to vehicle-treated mice at P20 (Fig. 4a; p < 0.01). Offspring of dex-treated mothers had significantly less total blood vessel length across all regions of the PVN (Fig. 4b; p < 0.01), while decreased branch points were restricted to the rostral and mid regions compared to vehicle-treated (Fig. 4c; p < 0.05). Brains perfused with FITC were also examined and dex-exposed offspring had less blood vessel density compared to vehicle-treated (data not shown). There were no significant differences in blood vessel length or branch points in the LH or CTX due to dex-treatment (data not shown). This indicates that prenatal exposure to dex impacts blood vessels within the PVN of young offspring.Fig. 4


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)

Prenatal exposure to dexamethasone (dex) impacted blood vessel density in the postnatal mouse paraventricular nucleus of the hypothalamus (PVN) at P20. There was a significant decrease in blood vessel length for the entire PVN for dex-treated compared to vehicle-treated mice (a, **p < 0.01). There was also a region-specific significant decrease in blood vessel length in the rostral, mid and caudal regions of the PVN in dex-treated compared to vehicle-treated mice (b, ***p < 0.0001). For branch points, there was only a significant decrease in the rostral and mid PVN in dex-treated compared to vehicle-treated mice (c, *p < 0.05). Number of animals per group (n = 8) is provided in the code for the bars in each panel
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Prenatal exposure to dexamethasone (dex) impacted blood vessel density in the postnatal mouse paraventricular nucleus of the hypothalamus (PVN) at P20. There was a significant decrease in blood vessel length for the entire PVN for dex-treated compared to vehicle-treated mice (a, **p < 0.01). There was also a region-specific significant decrease in blood vessel length in the rostral, mid and caudal regions of the PVN in dex-treated compared to vehicle-treated mice (b, ***p < 0.0001). For branch points, there was only a significant decrease in the rostral and mid PVN in dex-treated compared to vehicle-treated mice (c, *p < 0.05). Number of animals per group (n = 8) is provided in the code for the bars in each panel
Mentions: Blood vessels that are potentially newly formed and not yet fully functional are not identified by vascular perfusion with FITC (Frahm et al. 2013). Therefore, immunoreactive PECAM was utilized to visualize the more complete endothelial cell population. PECAM revealed an overall 13 % decrease in blood vessel length in the PVN for dex-treated compared to vehicle-treated mice at P20 (Fig. 4a; p < 0.01). Offspring of dex-treated mothers had significantly less total blood vessel length across all regions of the PVN (Fig. 4b; p < 0.01), while decreased branch points were restricted to the rostral and mid regions compared to vehicle-treated (Fig. 4c; p < 0.05). Brains perfused with FITC were also examined and dex-exposed offspring had less blood vessel density compared to vehicle-treated (data not shown). There were no significant differences in blood vessel length or branch points in the LH or CTX due to dex-treatment (data not shown). This indicates that prenatal exposure to dex impacts blood vessels within the PVN of young offspring.Fig. 4

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