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

Neurogenic niches in the developing brain. Dividing cells in the subventricular zone are closely associated with blood vessels, and the concept of a neurovascular niche (yellow), which reflects a zone of influence of vascular factors on neural progenitor cells, suggested in the adult and developmental subventricular zone. In early development, the dividing cells in the ventricular zone are not closely associated with the blood vasculature, but may be affected by trophic factors produced in the CSF, and therefore exist in a neuroglial-CSF niche. Cells from the ventricular zone migrate toward the neurovascular niche, before differentiating and migrating to outer cortical layers of the brain.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Neurogenic niches in the developing brain. Dividing cells in the subventricular zone are closely associated with blood vessels, and the concept of a neurovascular niche (yellow), which reflects a zone of influence of vascular factors on neural progenitor cells, suggested in the adult and developmental subventricular zone. In early development, the dividing cells in the ventricular zone are not closely associated with the blood vasculature, but may be affected by trophic factors produced in the CSF, and therefore exist in a neuroglial-CSF niche. Cells from the ventricular zone migrate toward the neurovascular niche, before differentiating and migrating to outer cortical layers of the brain.

Mentions: In the second half of gestation in the rodent, equivalent to the 1st—2nd trimester in humans (Clancy et al., 2001), there is no evidence of blood-brain barrier disruption associated with experimentally induced inflammation. However, there is substantial evidence for changes to the developing brain, which reflect changes in immune signaling. There is a reported decrease in (VZ) proliferation, but not the subventricular zone (SVZ), in response to low dose LPS-induced inflammation in mice at E13.5 of gestation (Stolp et al., 2011). The change in proliferation in the VZ but not the SVZ implies a variable contribution of the vasculature and the CSF for central immune signaling following induction of the systemic maternal inflammatory response (discussed further below), and indicate that the progenitor cells in the VZ and SVZ are in different environmental niches (Figure 3). Additional studies confirm the sensitivity of the VZ cell population to immune signaling, indicating presence of receptors to specific cytokines (e.g., IL-1β) or pathogen associated molecules (including TLR2 and 3) and stimulation of these receptors decrease neurogenesis and may alter cellular differentiation (Lathia et al., 2008; Okun et al., 2010; Crampton et al., 2012).


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)

Neurogenic niches in the developing brain. Dividing cells in the subventricular zone are closely associated with blood vessels, and the concept of a neurovascular niche (yellow), which reflects a zone of influence of vascular factors on neural progenitor cells, suggested in the adult and developmental subventricular zone. In early development, the dividing cells in the ventricular zone are not closely associated with the blood vasculature, but may be affected by trophic factors produced in the CSF, and therefore exist in a neuroglial-CSF niche. Cells from the ventricular zone migrate toward the neurovascular niche, before differentiating and migrating to outer cortical layers of the brain.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Neurogenic niches in the developing brain. Dividing cells in the subventricular zone are closely associated with blood vessels, and the concept of a neurovascular niche (yellow), which reflects a zone of influence of vascular factors on neural progenitor cells, suggested in the adult and developmental subventricular zone. In early development, the dividing cells in the ventricular zone are not closely associated with the blood vasculature, but may be affected by trophic factors produced in the CSF, and therefore exist in a neuroglial-CSF niche. Cells from the ventricular zone migrate toward the neurovascular niche, before differentiating and migrating to outer cortical layers of the brain.
Mentions: In the second half of gestation in the rodent, equivalent to the 1st—2nd trimester in humans (Clancy et al., 2001), there is no evidence of blood-brain barrier disruption associated with experimentally induced inflammation. However, there is substantial evidence for changes to the developing brain, which reflect changes in immune signaling. There is a reported decrease in (VZ) proliferation, but not the subventricular zone (SVZ), in response to low dose LPS-induced inflammation in mice at E13.5 of gestation (Stolp et al., 2011). The change in proliferation in the VZ but not the SVZ implies a variable contribution of the vasculature and the CSF for central immune signaling following induction of the systemic maternal inflammatory response (discussed further below), and indicate that the progenitor cells in the VZ and SVZ are in different environmental niches (Figure 3). Additional studies confirm the sensitivity of the VZ cell population to immune signaling, indicating presence of receptors to specific cytokines (e.g., IL-1β) or pathogen associated molecules (including TLR2 and 3) and stimulation of these receptors decrease neurogenesis and may alter cellular differentiation (Lathia et al., 2008; Okun et al., 2010; Crampton et al., 2012).

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