Barrier function in the peripheral and central nervous system—a review

Abstract

The peripheral (PNS) and central nervous system (CNS) are delicate structures, highly sensitive to homeostatic changes-and crucial for basic vital functions. Thus, a selection of barriers ensures the protection of the nervous system from noxious blood-borne or surrounding stimuli. In this chapter, anatomy and functioning of the blood-nerve (BNB), the blood-brain (BBB), and the blood-spinal cord barriers (BSCB) are presented and the key tight junction (TJ) proteins described: claudin-1, claudin-3, claudin-5, claudin-11, claudin-12, claudin-19, occludin, Zona occludens-1 (ZO-1), and tricellulin are by now identified as relevant for nerval barriers. Different diseases can lead to or be accompanied by neural barrier disruption, and impairment of these barriers worsens pathology. Peripheral nerve injury and inflammatory polyneuropathy cause an increased permeability of BNB as well as BSCB, while, e.g., diseases of the CNS such as amyotrophic lateral sclerosis, multiple sclerosis, spinal cord injury, or Alzheimer's disease can progress and worsen through barrier dysfunction. Moreover, the complex role and regulation of the BBB after ischemic stroke is described. On the other side, PNS and CNS barriers hamper the delivery of drugs in diseases when the barrier is intact, e.g., in certain neurodegenerative diseases or inflammatory pain. Understanding of the barrier - regulating processes has already lead to the discovery of new molecules as drug enhancers. In summary, the knowledge of all of these mechanisms might ultimately lead to the invention of drugs to control barrier function to help ameliorating or curing neurological diseases.

Virus entry and replication in the brain precedes blood-brain barrier disruption during intranasal alphavirus infection

“…The BBB occurs at the levels of capillaries and post-capillary venules, and results from the selectivity of TJs and AJs that restrict the passage of solutes, low expression of leukocyte adhesion molecules, and an additional layer of barrier support provided by ensheathing pericytes and astrocyte endfeet (Reinhold and Rittner, 2016). In our model VEEV entry into the CNS occurs along axons of olfactory sensory neurons, however modulation of the BBB may occur through mechanisms that are independent of the inoculation route.…”

Pathophysiological Changes of Physical Barriers of Peripheral Nerves After Injury

“…Besides endoneurial endothelium, perineurium is generally considered to be another critical structure that composes the blood-nerve barrier (Reinhold and Rittner, 2017). Light and electron microscopy studies revealed that there existed apparent and abundant tight junction strands between neighboring perineurial cells (Thomas, 1963; Gamble and Eames, 1964; Reale et al, 1975; Beamish et al, 1991).…”

“…These physical barriers in the peripheral nervous system may be altered and disrupted under various pathological conditions, especially many immune mediated neuropathies such as Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) (Kanda, 2013; Reinhold and Rittner, 2017; Skaper, 2017). Besides peripheral neuropathies, trauma to the peripheral nervous system can also lead to pathophysiological changes of these physical barriers (Mizisin and Weerasuriya, 2011; Reinhold and Rittner, 2017).…”

“…Besides peripheral neuropathies, trauma to the peripheral nervous system can also lead to pathophysiological changes of these physical barriers (Mizisin and Weerasuriya, 2011; Reinhold and Rittner, 2017). In the current review, we introduce anatomic components of the peripheral nervous system, describe cellular and molecular elements of physical barriers of peripheral nerves, and specifically discuss pathophysiological changes of these physical barriers following peripheral nerve injury.…”

Blood–spinal cord barrier breakdown and pericyte deficiency in peripheral neuropathy

“…A homeostatic microenvironment is of utmost importance to the function of the spinal cord in protection against external, blood‐borne influence. The blood–spinal cord barrier (BSCB) is formed by capillary endothelial cells, a basal lamina, pericytes, and astrocyte foot processes . Endothelial cells are characterized by an absence of cell membrane fenestrations.…”