Topographic Reorganization of Cerebrovascular Mural Cells under Seizure Conditions

Cell Rep. 2018 Apr 24;23(4):1045-1059. doi: 10.1016/j.celrep.2018.03.110.

Abstract

Reorganization of the neurovascular unit has been suggested in the epileptic brain, although the dynamics and functional significance remain unclear. Here, we tracked the in vivo dynamics of perivascular mural cells as a function of electroencephalogram (EEG) activity following status epilepticus. We segmented the cortical vascular bed to provide a size- and type-specific analysis of mural cell plasticity topologically. We find that mural cells are added and removed from veins, arterioles, and capillaries after seizure induction. Loss of mural cells is proportional to seizure severity and vascular pathology (e.g., rigidity, perfusion, and permeability). Treatment with platelet-derived growth factor subunits BB (PDGF-BB) reduced mural cell loss, vascular pathology, and epileptiform EEG activity. We propose that perivascular mural cells play a pivotal role in seizures and are potential targets for reducing pathophysiology.

Keywords: PDGF-BB; PDGFR-B; blood flow; epilepsy; in vivo microscopy; neurovascular; pericyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Becaplermin / genetics
  • Becaplermin / metabolism*
  • Capillary Permeability*
  • Cerebral Arteries* / metabolism
  • Cerebral Arteries* / pathology
  • Cerebral Arteries* / physiopathology
  • Cerebral Veins* / metabolism
  • Cerebral Veins* / pathology
  • Cerebral Veins* / physiopathology
  • Electroencephalography
  • Mice
  • Mice, Transgenic
  • Status Epilepticus* / genetics
  • Status Epilepticus* / metabolism
  • Status Epilepticus* / pathology
  • Status Epilepticus* / physiopathology

Substances

  • Becaplermin