Limits...
Immune responses at brain barriers and implications for brain development and neurological function in later life.

Stolp HB, Liddelow SA, Sá-Pereira I, Dziegielewska KM, Saunders NR - Front Integr Neurosci (2013)

Bottom Line: This signaling system appears to change both with normal ageing, and during disease.Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging.The implications of inflammation-induced barrier dysfunction for brain development and subsequent neurological function are also discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Perinatal Imaging and Health, King's College London London, UK ; Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, UK.

ABSTRACT
For a long time the brain has been considered an immune-privileged site due to a muted inflammatory response and the presence of protective brain barriers. It is now recognized that neuroinflammation may play an important role in almost all neurological disorders and that the brain barriers may be contributing through either normal immune signaling or disruption of their basic physiological mechanisms. The distinction between normal function and dysfunction at the barriers is difficult to dissect, partly due to a lack of understanding of normal barrier function and partly because of physiological changes that occur as part of normal development and ageing. Brain barriers consist of a number of interacting structural and physiological elements including tight junctions between adjacent barrier cells and an array of influx and efflux transporters. Despite these protective mechanisms, the capacity for immune-surveillance of the brain is maintained, and there is evidence of inflammatory signaling at the brain barriers that may be an important part of the body's response to damage or infection. This signaling system appears to change both with normal ageing, and during disease. Changes may affect diapedesis of immune cells and active molecular transfer, or cause rearrangement of the tight junctions and an increase in passive permeability across barrier interfaces. Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging. The implications of inflammation-induced barrier dysfunction for brain development and subsequent neurological function are also discussed.

No MeSH data available.


Related in: MedlinePlus

Neuroependymal cell uptake of plasma proteins from the CSF. Coronal, paraffin-embedded section of lateral ventricular wall from sheep fetuses at embryonic day 40 (E40, A), E60 (B), and E15 mouse (C) stained to detect endogenous plasma protein. The migrating neurons in the ventricular zone are strongly stained (arrows), blood vessels also show a positive staining reaction (unfilled arrowhead). Protein is also seen precipitated in the CSF (filled arrowheads). Extensive precipitation of CSF plasma protein can be seen in the embryonic mouse example displayed in panel (C) (arrowheads, also in A,B). Choroid plexus epithelial cells individually positive for protein can also be seen in panel (A) (asterisks). Abbreviations: csf, cerebrospinal fluid; lvcp, lateral ventricular choroid plexus. Scale bars 50 μm in each.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3750212&req=5

Figure 2: Neuroependymal cell uptake of plasma proteins from the CSF. Coronal, paraffin-embedded section of lateral ventricular wall from sheep fetuses at embryonic day 40 (E40, A), E60 (B), and E15 mouse (C) stained to detect endogenous plasma protein. The migrating neurons in the ventricular zone are strongly stained (arrows), blood vessels also show a positive staining reaction (unfilled arrowhead). Protein is also seen precipitated in the CSF (filled arrowheads). Extensive precipitation of CSF plasma protein can be seen in the embryonic mouse example displayed in panel (C) (arrowheads, also in A,B). Choroid plexus epithelial cells individually positive for protein can also be seen in panel (A) (asterisks). Abbreviations: csf, cerebrospinal fluid; lvcp, lateral ventricular choroid plexus. Scale bars 50 μm in each.

Mentions: So very little is known about the cellular and molecular properties of the CSF-brain interface in the developing brain that is not even clear if the transport mechanisms at this interface function similarly to other barriers. It is known that at some early stages of brain development, at a time when strap junctions are present at the CSF-brain interface (see above), plasma-derived proteins found in the CSF (which are present in a much higher concentration than in adult CSF, Dziegielewska et al., 1988) are taken up by some of the neuroependymal cells lining the ventricular system (Figure 2). This phenomenon has been described for both endogenous proteins (e.g., alpha 2-HS glycoprotein in human fetuses—Møllgård et al., 1988) and exogenously administered non-native proteins (e.g., human albumin injected into the wallaby—Dziegielewska et al., 1988; or rat—Balslev et al., 1997). Examples of plasma protein staining in different animal species are shown in Figure 2. It is not known, however, if this is selective with respect to individual proteins (as is seen in the choroid plexus, Liddelow et al., 2009), regions of the ventricular system or stage of brain development. It is also unclear whether the functional significance of this protein uptake lies in the ligands known to be bound to many of these proteins (e.g., growth factors, vitamins) or in some specific properties of the individual proteins themselves. It is also unknown if this internal barrier is able to impede any CNS immune response.


Immune responses at brain barriers and implications for brain development and neurological function in later life.

Stolp HB, Liddelow SA, Sá-Pereira I, Dziegielewska KM, Saunders NR - Front Integr Neurosci (2013)

Neuroependymal cell uptake of plasma proteins from the CSF. Coronal, paraffin-embedded section of lateral ventricular wall from sheep fetuses at embryonic day 40 (E40, A), E60 (B), and E15 mouse (C) stained to detect endogenous plasma protein. The migrating neurons in the ventricular zone are strongly stained (arrows), blood vessels also show a positive staining reaction (unfilled arrowhead). Protein is also seen precipitated in the CSF (filled arrowheads). Extensive precipitation of CSF plasma protein can be seen in the embryonic mouse example displayed in panel (C) (arrowheads, also in A,B). Choroid plexus epithelial cells individually positive for protein can also be seen in panel (A) (asterisks). Abbreviations: csf, cerebrospinal fluid; lvcp, lateral ventricular choroid plexus. Scale bars 50 μm in each.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750212&req=5

Figure 2: Neuroependymal cell uptake of plasma proteins from the CSF. Coronal, paraffin-embedded section of lateral ventricular wall from sheep fetuses at embryonic day 40 (E40, A), E60 (B), and E15 mouse (C) stained to detect endogenous plasma protein. The migrating neurons in the ventricular zone are strongly stained (arrows), blood vessels also show a positive staining reaction (unfilled arrowhead). Protein is also seen precipitated in the CSF (filled arrowheads). Extensive precipitation of CSF plasma protein can be seen in the embryonic mouse example displayed in panel (C) (arrowheads, also in A,B). Choroid plexus epithelial cells individually positive for protein can also be seen in panel (A) (asterisks). Abbreviations: csf, cerebrospinal fluid; lvcp, lateral ventricular choroid plexus. Scale bars 50 μm in each.
Mentions: So very little is known about the cellular and molecular properties of the CSF-brain interface in the developing brain that is not even clear if the transport mechanisms at this interface function similarly to other barriers. It is known that at some early stages of brain development, at a time when strap junctions are present at the CSF-brain interface (see above), plasma-derived proteins found in the CSF (which are present in a much higher concentration than in adult CSF, Dziegielewska et al., 1988) are taken up by some of the neuroependymal cells lining the ventricular system (Figure 2). This phenomenon has been described for both endogenous proteins (e.g., alpha 2-HS glycoprotein in human fetuses—Møllgård et al., 1988) and exogenously administered non-native proteins (e.g., human albumin injected into the wallaby—Dziegielewska et al., 1988; or rat—Balslev et al., 1997). Examples of plasma protein staining in different animal species are shown in Figure 2. It is not known, however, if this is selective with respect to individual proteins (as is seen in the choroid plexus, Liddelow et al., 2009), regions of the ventricular system or stage of brain development. It is also unclear whether the functional significance of this protein uptake lies in the ligands known to be bound to many of these proteins (e.g., growth factors, vitamins) or in some specific properties of the individual proteins themselves. It is also unknown if this internal barrier is able to impede any CNS immune response.

Bottom Line: This signaling system appears to change both with normal ageing, and during disease.Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging.The implications of inflammation-induced barrier dysfunction for brain development and subsequent neurological function are also discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Perinatal Imaging and Health, King's College London London, UK ; Department of Physiology, Anatomy and Genetics, University of Oxford Oxford, UK.

ABSTRACT
For a long time the brain has been considered an immune-privileged site due to a muted inflammatory response and the presence of protective brain barriers. It is now recognized that neuroinflammation may play an important role in almost all neurological disorders and that the brain barriers may be contributing through either normal immune signaling or disruption of their basic physiological mechanisms. The distinction between normal function and dysfunction at the barriers is difficult to dissect, partly due to a lack of understanding of normal barrier function and partly because of physiological changes that occur as part of normal development and ageing. Brain barriers consist of a number of interacting structural and physiological elements including tight junctions between adjacent barrier cells and an array of influx and efflux transporters. Despite these protective mechanisms, the capacity for immune-surveillance of the brain is maintained, and there is evidence of inflammatory signaling at the brain barriers that may be an important part of the body's response to damage or infection. This signaling system appears to change both with normal ageing, and during disease. Changes may affect diapedesis of immune cells and active molecular transfer, or cause rearrangement of the tight junctions and an increase in passive permeability across barrier interfaces. Here we review the many elements that contribute to brain barrier functions and how they respond to inflammation, particularly during development and aging. The implications of inflammation-induced barrier dysfunction for brain development and subsequent neurological function are also discussed.

No MeSH data available.


Related in: MedlinePlus