CNS Barriers: Identifying Knowledge Gaps and Addressing Pending Questions

Dear Colleagues,

Insulation of the nervous system from other body compartments is a standing prerequisite for proper neuronal function that has been conserved throughout evolution.  The interface that separates the nervous system from the circulatory system is known as the blood-brain barrier (BBB) and hemolymph-brain barrier in vertebrates and invertebrates, respectively. While these barriers are functionally conserved, their anatomy varies across taxa.

Invertebrates and primitive vertebrates have their neurophil ensheathed by a glial barrier. Vertebrates, on the other hand, have evolved a more complex structure composed of various cell types that vascularize the brain. Regardless of the level of complexity of such barriers they all serve as gatekeepers that maintain homeostasis, control supply of nutrients and prevent the entry of harmful substances. 

In addition to the BBB, the CNS is guarded by various barriers such as blood-cerebrospinal fluid barrier, meningeal barrier, blood-retinal barrier and barriers engulfing lesion core. The BBB is the most studied of all perhaps due to its direct involvement in regulating passage to the brain parenchyma. Despite the large volume of literature on this topic many questions and knowledge gaps remain to be addressed. Precise knowledge of aspects like:

(a) temporal mapping of barrier genesis and developmental stages;(b) region-specific heterogeneity in barrier properties;(c) barrier capacity to adapt to changes in the CNS environment, is currently lacking.

Moreover, key questions such as:

1. Do barrier properties change across different life stages or different times of the day as part of normal physiology?
2. It has been shown that changes in physiological factors like physical or mental activity, and metabolic rate induce alterations in the blood flow, however, do their impact extended to modifying the properties or function of the cellular or molecular components of the barrier?
3. Pathology is usually linked to compromised barrier integrity and subsequently increased permissiveness or leakage, however, it would be interesting to learn if conditions causing an overly restrictive barrier do exist and what pathological consequences they may lead to?

In this issue, we will curate the latest findings and views with the aim to improve our understanding of the biogenesis and function of CNS barriers. Manuscripts answering open questions, addressing knowledge gaps or summarizing current research related to all types of CNS barriers in vertebrates as well as invertebrates are welcome. 

Dr. Bashayer Al Mubarak
Guest Editor

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