The choroid plexus is a key cerebral invasion route for T cells after stroke

Acta Neuropathol. 2017 Dec;134(6):851-868. doi: 10.1007/s00401-017-1758-y. Epub 2017 Jul 31.

Abstract

Neuroinflammation contributes substantially to stroke pathophysiology. Cerebral invasion of peripheral leukocytes-particularly T cells-has been shown to be a key event promoting inflammatory tissue damage after stroke. While previous research has focused on the vascular invasion of T cells into the ischemic brain, the choroid plexus (ChP) as an alternative cerebral T-cell invasion route after stroke has not been investigated. We here report specific accumulation of T cells in the peri-infarct cortex and detection of T cells as the predominant population in the ipsilateral ChP in mice as well as in human post-stroke autopsy samples. T-cell migration from the ChP to the peri-infarct cortex was confirmed by in vivo cell tracking of photoactivated T cells. In turn, significantly less T cells invaded the ischemic brain after photothrombotic lesion of the ipsilateral ChP and in a stroke model encompassing ChP ischemia. We detected a gradient of CCR2 ligands as the potential driving force and characterized the neuroanatomical pathway for the intracerebral migration. In summary, our study demonstrates that the ChP is a key invasion route for post-stroke cerebral T-cell invasion and describes a CCR2-ligand gradient between cortex and ChP as the potential driving mechanism for this invasion route.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Animals
  • Brain Injuries, Traumatic / pathology
  • Brain Injuries, Traumatic / physiopathology
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology*
  • Cell Movement / physiology*
  • Cerebral Cortex / pathology
  • Cerebral Cortex / physiopathology
  • Chemokine CCL2 / metabolism
  • Choroid Plexus / pathology
  • Choroid Plexus / physiopathology*
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myeloid Cells / pathology
  • Myeloid Cells / physiology
  • Stroke / pathology
  • Stroke / physiopathology*
  • T-Lymphocytes / pathology
  • T-Lymphocytes / physiology*

Substances

  • Ccl2 protein, mouse
  • Chemokine CCL2