Astrocyte barriers to neurotoxic inflammation

By M. Sofroniew. Nature Reviews Neuroscience, 2015

1,089 citations recorded by the source corpus.

Astrocytes form borders (glia limitans) that separate neural from non-neural tissue along perivascular spaces, meninges and tissue lesions in the CNS. Transgenic loss-of-function studies reveal that astrocyte borders and scars serve as functional barriers that restrict the entry of inflammatory cells into CNS parenchyma in health and disease. Astrocytes also have powerful pro-inflammatory potential. Thus, astrocytes are emerging as pivotal regulators of CNS inflammatory responses. This Review discusses evidence that astrocytes have crucial roles in attracting and restricting CNS inflammation, with important implications for diverse CNS disorders.

Subfields: Biological Psychiatry, Neurology, Physiology

View Paper: https://www.semanticscholar.org/paper/ddcc105905db13ff418945566d20235310d8b5e6

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Citations in the corpus

Neuroinflammation and depression: A review (2020, background): “Adult new-born neurons are regulated by different components of the neurogenic niche, including microglia and astrocytes (Gonçalves et al., 2016; Hanisch & Kettenmann, 2007; de Miranda, Zhang, Katsumoto, & Teixeira, 2017; Sofroniew, 2015).”
Astrocyte crosstalk in CNS inflammation (2020, background): “Astrocyte-derived VEGF plays a central role in this process and participates in a signaling cascade that eventually results in increased BBB permeability (Sofroniew, 2015b).”
Spinal cord injury: molecular mechanisms and therapeutic interventions (2023, background): “The astrocyte scar is narrow, with only several cell layers separating the spare neural tissue from the nonneural lesion core, and its layers are continuous with the spare but reactive neural tissue.(141,171,177) Experimental evidence revealed the beneficial aspects of the astrocyte scar.”
Reactive Astrocytes: Production, Function, and Therapeutic Potential. (2017, background): “Inflammatory responses are a major part of all central nervous system (CNS) insults, including acute trauma, infection, and chronic neurodegenerative diseases (see Sofroniew, 2015).”
Astrocyte reactivity: Subtypes, states and functions in CNS innate immunity (2020, background): “molecules, including membrane receptors, transcriptional regulators, or effector molecules, can exacerbate tissue injury and worsen functional outcome in models of essentially all forms of CNS disorders, including infection [19], traumatic injury [65], autoimmune attack [14, 15, 70]; stroke [45, 71]”
Physiology of Astroglia. (2018, neutral): “Finally, through mounting reactive response, astrocytes (together with microglia) represent the main defensive system of the CNS (we shall not discuss astrogliopathology in the present paper, instead recommending recent comprehensive reviews (257, 258, 1329, 1352, 1353, 1637, 1638, 1815, 1818).”
The blood-brain barrier in systemic inflammation. (2017, neutral): “, 2012), and astrocytes are capable of producing a range of substances associated with disruptive BBB change, including interleukin-1b (IL-1b), interleukin-6 (IL-6), TNFa, and prostaglandins (Sofroniew, 2015).”
Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and CNS inflammation via the aryl hydrocarbon receptor (2016, neutral): “Astrocyte-produced factors modulate the polarization of microglia and monocytes, and may also have direct neurotoxic effects 8,11 .”
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020, background): “Abbreviations AD: Alzheimer’s disease; APOE: Apolipoprotein E; Aβ: β-Amyloid; APP: Amyloid precursor protein; KCC2: K-Cl cotransporter 2; GABA : γaminobutyric acid; sAPP: Soluble amyloid precursor proteins; CNS: Central nervous system; PS1/2: Presenilins 1/2; CSF: Cerebral spinal fluid; LRP1: Lowden”