Paravascular pathways contribute to vasculitis and neuroinflammation after subarachnoid hemorrhage independently of glymphatic control

Cell Death Dis. 2016 Mar 31;7(3):e2160. doi: 10.1038/cddis.2016.63.

Abstract

Subarachnoid hemorrhage (SAH) is a devastating disease with high mortality. The mechanisms underlying its pathological complications have not been fully identified. Here, we investigate the potential involvement of the glymphatic system in the neuropathology of SAH. We demonstrate that blood components rapidly enter the paravascular space following SAH and penetrate into the perivascular parenchyma throughout the brain, causing disastrous events such as cerebral vasospasm, delayed cerebral ischemia, microcirculation dysfunction and widespread perivascular neuroinflammation. Clearance of the paravascular pathway with tissue-type plasminogen activator ameliorates the behavioral deficits and alleviates histological injury of SAH. Interestingly, AQP4(-/-) mice showed no improvements in neurological deficits and neuroinflammation at day 7 after SAH compared with WT control mice. In conclusion, our study proves that the paravascular pathway dynamically mediates the pathological complications following acute SAH independently of glymphatic control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Aquaporin 4 / deficiency
  • Aquaporin 4 / genetics
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / metabolism
  • Disease Models, Animal
  • Female
  • Humans
  • Inflammation / etiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Middle Aged
  • Retrospective Studies
  • Subarachnoid Hemorrhage / diagnostic imaging
  • Subarachnoid Hemorrhage / metabolism
  • Subarachnoid Hemorrhage / pathology*
  • Tomography, X-Ray Computed
  • Vasculitis / etiology*
  • Vasospasm, Intracranial / diagnostic imaging
  • Vasospasm, Intracranial / metabolism
  • Vasospasm, Intracranial / pathology*
  • Young Adult

Substances

  • Aqp4 protein, mouse
  • Aquaporin 4