Astrocytes in the tempest of multiple sclerosis

Abstract

Astrocytes are the most abundant cell population within the CNS of mammals. Their glial role is perfectly performed in the healthy CNS as they support functions of neurons. The omnipresence of astrocytes throughout the white and grey matter and their intimate relation with blood vessels of the CNS, as well as numerous immunity‐related actions that these cells are capable of, imply that astrocytes should have a prominent role in neuroinflammatory disorders, such as multiple sclerosis (MS). The role of astrocytes in MS is rather ambiguous, as they have the capacity to both stimulate and restrain neuroinflammation and tissue destruction. In this paper we present some of the proved and the proposed functions of astrocytes in neuroinflammation and discuss the effect of MS therapeutics on astrocytes.

Hyaluronan synthesis is necessary for autoreactive T-cell trafficking, activation, and Th1 polarization

“…Historically, the role of astrocytes in neuroinflammation has been thought to be limited to a secondary response to injury, creating an inert astroglial scar that prevents further damage. However, more recent findings suggest that, depending on the context, (aberrant) astrogliosis could play a pathological role in a variety of neurological diseases, including MS (41,42). It has been shown that astrogliosis is a major component contributing to HA deposition in EAE lesions (14,22).…”

Gene expression profiling of the astrocyte transcriptome in multiple sclerosis normal appearing white matter reveals a neuroprotective role

“…While it has been suggested that astrocytes play a neuroprotective role in MS by inhibiting demyelination (Miljkovic et al, 2011), releasing anti-inflammatory cytokines (Bsibsi et al, 2006) and secreting proteins involved in myelin repair and neurotrophins to support regeneration of neurons (Marz et al, 1999, Moore et al, 2011a, Moore et al, 2011b, Mason et al, 2001, Miljkovic et al, 2011, it has also been proposed that astrocytes are detrimental in disease pathogenesis by releasing proinflammatory cytokines, contributing to BBB dysfunction (Argaw et al, 2006, Argaw et al, 2012 and preventing oligodendrocyte precursor cell (OPC) maturation into remyelinating oligodendrocytes (Messersmith et al, 2000, Sarchielli et al, 2008.…”

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

“…NO also restrains the encephalitogenic T cell response [8] . Astrocytes are intensively involved in limiting the encephalitogenic immune response [9] . For instance, they express CXCL12, which has been attributed an anti-inflammatory role in neuroinflammation [10] .…”