Neuroinflammation: A Common Pathway in CNS Diseases as Mediated at the Blood-Brain Barrier

Abstract

The blood-brain barrier (BBB) is not simply a physical barrier but a regulatory interface between the central nervous system (CNS) and immune system. The BBB both affects and is affected by the immune system and connects at many levels with the CNS, including the following: (1) the BBB transports cytokines and secretes various substances with neuroinflammatory properties; (2) transporters are altered in disease states including traumatic injury, Alzheimer’s disease and inflammatory processes; (3) cytokines and other immune secretions from the cells comprising the BBB are both constitutive and inducible; (4) immune cells are transported across the BBB by the highly regulated process termed diapedesis, which involves communication and interactions between the brain endothelial cells and the immune cells; (5) the neuroimmune system has various effects on the BBB, including modulation of important transport systems and in extreme pathological conditions even disruption of the BBB, and (6) the brain-to-blood efflux transporter P-glycoprotein is altered in inflammatory conditions, thus affecting drug delivery to the brain. In summary, the BBB is an interactive interface that regulates and defines many of the ways that the CNS and the immune system communicate with one another.

Comparing mechanisms of host manipulation across host and parasite taxa

“…We now know that the brain contains native immunoreactive components, where microglia, astrocytes and even neurons have pathogen-detecting receptors on their cell surfaces (Falsig et al, 2008). In fact, the brain can increase its immune reactivity when invaded by parasites or pathogens, which can be enhanced through transport by specific blood-brain barrier transporter proteins (Erickson et al, 2012). Therefore, the key benefit of parasitizing the CNS appears to be behavioral manipulation.…”

“…They also activate in response to tissue damage to promote healing and scar formation. In the CNS, fibroblasts have a neuroprotective role and can promote neurogenesis (Erickson et al, 2012;Guillemot and Zimmer, 2011). It remains unclear why metacercariae would promote fibroblast activity near their cysts walls, but inhibition of the fibroblast growth factors appeared to disrupt the ability of the metacercariae to aggregate in vitro (J. LaClair and K.D.L., unpublished data).…”

Betulinic acid regulates generation of neuroinflammatory mediators responsible for tissue destruction in multiple sclerosis in vitro

“…Special attention should be given to the Although data on the ability of BA to cross an intact bloodbrain barrier (BBB) are, to the best of our knowledge, unavailable, it is conceivable that a complex triterpenoid compound such as BA does not passively cross this barrier. However, during neuroinflammation, eg in EAE, the BBB is affected as well, and it becomes more permeable for transport of complex molecules [33] . The possibility of barrier circumvention, through BBB disruption, prodrugs, molecular Trojan horses or nanocarriers, should also be considered [34] .…”

Advances in Neuroimmunology

“…Cells of the brain, primarily glia cells (e.g., astrocytes and microglia) but also neurons under some conditions, produce a large number of immune factors. In addition, endothelial cells of the brain and peripheral immune cells that enter the brain can contribute to the immune environment of the brain [3].In general, pathological conditions are associated with elevated levels of neuroimmune factors in the brain, whereas low levels of neuroimmune factors are found in the normal brain. For example, elevated levels of neuroimmune factors in the brain have been reported for a number of conditions including brain injury, infection, neurodegenerative and psychiatric disorders, and drug abuse [4][5][6].…”