4.6 Review

The role of neutrophils in the dysfunction of central nervous system barriers

Journal

FRONTIERS IN AGING NEUROSCIENCE
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2022.965169

Keywords

neutrophils; blood-brain barrier; blood-cerebrospinal fluid barrier (BCSFB); neurodegenerative diseases; neuroinflammation

Funding

  1. European Research Council (ERC) [695714]
  2. ERC [693606, 101069397]
  3. Italian Ministry of University and Research
  4. Alzheimer's Drug Discovery Foundation (ADDF), USA
  5. National Centers Program (National Biodiversity Future Center -NBFC)
  6. Fondazione Italiana Sclerosi Multipla (FISM), Genoa, Italy project [2019/PR-single/044]
  7. INVITE European Union's Horizon 2020 research and innovation program [754345]
  8. Fondazione Umberto Veronesi
  9. Marie Curie Actions (MSCA) [754345] Funding Source: Marie Curie Actions (MSCA)
  10. European Research Council (ERC) [101069397, 693606] Funding Source: European Research Council (ERC)

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Neutrophil migration plays a crucial role in the development of neurological diseases with inflammatory components. These cells can damage the blood-brain barrier and the blood-cerebrospinal fluid barrier, leading to significant tissue damage.
Leukocyte migration into the central nervous system (CNS) represents a central process in the development of neurological diseases with a detrimental inflammatory component. Infiltrating neutrophils have been detected inside the brain of patients with several neuroinflammatory disorders, including stroke, multiple sclerosis and Alzheimer's disease. During inflammatory responses, these highly reactive innate immune cells can rapidly extravasate and release a plethora of pro-inflammatory and cytotoxic factors, potentially inducing significant collateral tissue damage. Indeed, several studies have shown that neutrophils promote blood-brain barrier damage and increased vascular permeability during neuroinflammatory diseases. Recent studies have shown that neutrophils migrate into the meninges and choroid plexus, suggesting these cells can also damage the blood-cerebrospinal fluid barrier (BCSFB). In this review, we discuss the emerging role of neutrophils in the dysfunction of brain barriers across different neuroinflammatory conditions and describe the molecular basis and cellular interplays involved in neutrophil-mediated injury of the CNS borders.

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