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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

Blood vessels in the paraventricular nucleus of the hypothalamus (PVN) were wider than in the mouse cortex (CTX) at P12 and P52. Higher magnification of blood vessels at P52 visualized with fluorescein isothiocyanate perfusion in the CTX, lateral hypothalamus (LH) and PVN show that desmin morphology varied between brain regions with the PVN (c) having more of a wrapping pattern compared to the CTX (a) and LH (b). The wrapping may be related to a significantly greater blood vessel width in the PVN compared to the CTX at P12 and P22 (d, p < 0.05). There were no significant differences at P22 or in the LH when compared with the CTX or PVN at any age. Number of animals per group (n = 5) is provided in the code for the bars panels j and k. Significant differences between regions indicated by asterisk. Scale bar 20 µm in panel a, which applies to all images
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Fig3: Blood vessels in the paraventricular nucleus of the hypothalamus (PVN) were wider than in the mouse cortex (CTX) at P12 and P52. Higher magnification of blood vessels at P52 visualized with fluorescein isothiocyanate perfusion in the CTX, lateral hypothalamus (LH) and PVN show that desmin morphology varied between brain regions with the PVN (c) having more of a wrapping pattern compared to the CTX (a) and LH (b). The wrapping may be related to a significantly greater blood vessel width in the PVN compared to the CTX at P12 and P22 (d, p < 0.05). There were no significant differences at P22 or in the LH when compared with the CTX or PVN at any age. Number of animals per group (n = 5) is provided in the code for the bars panels j and k. Significant differences between regions indicated by asterisk. Scale bar 20 µm in panel a, which applies to all images

Mentions: Concerning postnatal and region-specific pericyte development, results showed significantly greater desmin-immunoreactive pericyte coverage at P22 and P52 compared to P12 (Fig. 2a–i; p < 0.01). For different brain regions, there was significantly more desmin-immunoreactive pericyte coverage at P12 in the PVN (Fig. 2g–i) compared to the LH (Fig. 2d–f) and CTX (Fig. 2a–c). For the CTX, there was a significant increase in desmin-immunoreactive pericyte coverage between P12 and P22 (Fig. 2a, b, j, k). At all ages examined, the PVN had significantly more desmin-immunoreactive pericyte coverage than the LH and the CTX (Fig. 2j; p < 0.01). When blood vessel density was taken into account, the PVN still had significantly more desmin-immunoreactive pericyte coverage than the CTX (Fig. 2k; p < 0.05). At P52, this increase in desmin-immunoreactive pericyte coverage was due to the morphology of the pericytes in the PVN (Fig. 3c) compared to the CTX (Fig. 3a). Desmin in the adult mouse labels processes running along small diameter and encircling larger diameter capillaries (Hellstrom et al. 1999). The pattern of desmin-immunoreactive pericyte coverage in the PVN showed a wrapping pattern around blood vessels while in the CTX more often it extended along the blood vessels. There were no differences in desmin-immunoreactive pericyte coverage in the LH (Fig. 3b) compared to the CTX or PVN after 50 days of age. To determine if the difference in pericyte coverage coincided with the size of blood vessels, blood vessel width was quantified (Fig. 3). Blood vessel widths were greater in the hypothalamus (LH––Fig. 3b, PVN––Fig. 3c) compared to the CTX (Fig. 3a). Quantification showed a statistically significant greater blood vessel width in the PVN (but not the LH) compared to the CTX (Fig. 3d; p < 0.05) indicating that at P52, the greater desmin-immunoreactive pericyte coverage in the PVN (Fig. 2i–k) was associated with an increase in blood vessel width (Fig. 3d). To examine if this was due to the presence of larger arterioles, antibodies against smooth muscle actin (SMA), a marker for smooth muscle cells that surround cerebral arteries or arterioles (Ladecola 2004) was examined. SMA immunoreactivity was observed in the brain, however, not within the PVN (data not shown) suggesting the larger width of blood vessels within the PVN was not due to the presence of arterioles, although this did not rule out the presence of venules. In general, desmin-positive pericyte coverage increased postnatally, varied between brain regions, and was related to blood vessel width.Fig. 3


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)

Blood vessels in the paraventricular nucleus of the hypothalamus (PVN) were wider than in the mouse cortex (CTX) at P12 and P52. Higher magnification of blood vessels at P52 visualized with fluorescein isothiocyanate perfusion in the CTX, lateral hypothalamus (LH) and PVN show that desmin morphology varied between brain regions with the PVN (c) having more of a wrapping pattern compared to the CTX (a) and LH (b). The wrapping may be related to a significantly greater blood vessel width in the PVN compared to the CTX at P12 and P22 (d, p < 0.05). There were no significant differences at P22 or in the LH when compared with the CTX or PVN at any age. Number of animals per group (n = 5) is provided in the code for the bars panels j and k. Significant differences between regions indicated by asterisk. Scale bar 20 µm in panel a, which applies to all images
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig3: Blood vessels in the paraventricular nucleus of the hypothalamus (PVN) were wider than in the mouse cortex (CTX) at P12 and P52. Higher magnification of blood vessels at P52 visualized with fluorescein isothiocyanate perfusion in the CTX, lateral hypothalamus (LH) and PVN show that desmin morphology varied between brain regions with the PVN (c) having more of a wrapping pattern compared to the CTX (a) and LH (b). The wrapping may be related to a significantly greater blood vessel width in the PVN compared to the CTX at P12 and P22 (d, p < 0.05). There were no significant differences at P22 or in the LH when compared with the CTX or PVN at any age. Number of animals per group (n = 5) is provided in the code for the bars panels j and k. Significant differences between regions indicated by asterisk. Scale bar 20 µm in panel a, which applies to all images
Mentions: Concerning postnatal and region-specific pericyte development, results showed significantly greater desmin-immunoreactive pericyte coverage at P22 and P52 compared to P12 (Fig. 2a–i; p < 0.01). For different brain regions, there was significantly more desmin-immunoreactive pericyte coverage at P12 in the PVN (Fig. 2g–i) compared to the LH (Fig. 2d–f) and CTX (Fig. 2a–c). For the CTX, there was a significant increase in desmin-immunoreactive pericyte coverage between P12 and P22 (Fig. 2a, b, j, k). At all ages examined, the PVN had significantly more desmin-immunoreactive pericyte coverage than the LH and the CTX (Fig. 2j; p < 0.01). When blood vessel density was taken into account, the PVN still had significantly more desmin-immunoreactive pericyte coverage than the CTX (Fig. 2k; p < 0.05). At P52, this increase in desmin-immunoreactive pericyte coverage was due to the morphology of the pericytes in the PVN (Fig. 3c) compared to the CTX (Fig. 3a). Desmin in the adult mouse labels processes running along small diameter and encircling larger diameter capillaries (Hellstrom et al. 1999). The pattern of desmin-immunoreactive pericyte coverage in the PVN showed a wrapping pattern around blood vessels while in the CTX more often it extended along the blood vessels. There were no differences in desmin-immunoreactive pericyte coverage in the LH (Fig. 3b) compared to the CTX or PVN after 50 days of age. To determine if the difference in pericyte coverage coincided with the size of blood vessels, blood vessel width was quantified (Fig. 3). Blood vessel widths were greater in the hypothalamus (LH––Fig. 3b, PVN––Fig. 3c) compared to the CTX (Fig. 3a). Quantification showed a statistically significant greater blood vessel width in the PVN (but not the LH) compared to the CTX (Fig. 3d; p < 0.05) indicating that at P52, the greater desmin-immunoreactive pericyte coverage in the PVN (Fig. 2i–k) was associated with an increase in blood vessel width (Fig. 3d). To examine if this was due to the presence of larger arterioles, antibodies against smooth muscle actin (SMA), a marker for smooth muscle cells that surround cerebral arteries or arterioles (Ladecola 2004) was examined. SMA immunoreactivity was observed in the brain, however, not within the PVN (data not shown) suggesting the larger width of blood vessels within the PVN was not due to the presence of arterioles, although this did not rule out the presence of venules. In general, desmin-positive pericyte coverage increased postnatally, varied between brain regions, and was related to blood vessel width.Fig. 3

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