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

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.

Brain Barriers and a Subpopulation of Astroglial Progenitors of Developing Human Forebrain Are Immunostained for the Glycoprotein YKL-40

“…In addition, within the neuroectoderm, per se, 4) there is a barrier interface between the CSF and the brain interstitial fluid at the apical neuroepithelial membrane (Saunders et al 2008) lined by dense YKL-40 immunoreactivity in the early brain. An important interface in the early steps of the brain barrier development is the blood-CSF barrier (Stolp et al 2013) where we found strong YKL-40 mRNA expression in the choroid plexus. Prominent YKL-40 staining was evident as early as 7 wpc (49 dpc) when the choroid plexus of the lateral ventricles first appears in the human embryonic brain.…”

“…We showed unique mRNA expression of YKL-40 in the human fetal choroid plexus (Johansen et al 2007), a prominent part of the brain barrier system involved in the process of neuroinflammation (Stolp et al 2013). The distribution of YKL-40 in the developing human forebrain and its possible role in brain barrier sites is unknown.…”

“…Bonneh-Barkay et al also propose that YKL-40 is correlated with reactive gliosis, particularly in response to neuroinflammation Bonneh-Barkay et al 2010). Accumulated work in the field suggests that neuroinflammation is of great importance in almost all neurological disorders, and that interactions between the brain barriers and the immune system contribute to this process (Stolp et al 2013).…”

Nanoneurology - Drug Delivery across the Brain Protective Barriers

“…Both (a) and (b) extend down the spinal cord; (c) the outer CSF-brain barrier formed by tight junctions between endothelial cells of the arachnoid vessels (pia arachnoid); and (d) the inner CSF-brain barrier formed by strap junctions between the neuro-ependymal cells lining the ventricular surfaces. It is present only in early development and absent in the adult [1]. The above barriers and the blood retinal barrier (not studied here) are parts of a whole realm of barriers.…”

Beyond the borders: The gates and fences of Neuroimmune interaction

“…It contains four sections; in the first section three papers describe the gates and fences for neuroimmune interactions directly at the central nervous system. Stolp et al (2013) The second section includes two reviews emphasizing the role of hormones on neuro-immune interactions. Quintanar and Guzmán-Soto (2013) describe the role of hypothalamic neurohormones in peripheral immune responses, including the clinical relevance of those hormones.…”