Chronic stress induced disruption of the peri-infarct neurovascular unit following experimentally induced photothrombotic stroke

J Cereb Blood Flow Metab. 2017 Dec;37(12):3709-3724. doi: 10.1177/0271678X17696100. Epub 2017 Mar 17.

Abstract

How stress influences brain repair is an issue of considerable importance, as patients recovering from stroke are known to experience high and often unremitting levels of stress post-event. In the current study, we investigated how chronic stress modified the key cellular components of the neurovascular unit. Using an experimental model of focal cortical ischemia in male C57BL/6 mice, we examined how exposure to a persistently aversive environment, induced by the application of chronic restraint stress, altered the cortical remodeling post-stroke. We focused on systematically investigating changes in the key components of the neurovascular unit (i.e. neurons, microglia, astrocytes, and blood vessels) within the peri-infarct territories using both immunohistochemistry and Western blotting. The results from our study indicated that exposure to chronic stress exerted a significant suppressive effect on each of the key cellular components involved in neurovascular remodeling. Co-incident with these cellular changes, we observed that chronic stress was associated with an exacerbation of motor impairment 42 days post-event. Collectively, these results highlight the vulnerability of the peri-infarct neurovascular unit to the negative effects of chronic stress.

Keywords: Stroke; chronic stress; glial cells; neuroinflammation; neurovascular unit.

MeSH terms

  • Animals
  • Astrocytes / pathology
  • Brain / blood supply
  • Brain / pathology*
  • Brain / physiopathology
  • Brain Ischemia / complications*
  • Brain Ischemia / pathology*
  • Brain Ischemia / physiopathology
  • Cell Count
  • Male
  • Mice, Inbred C57BL
  • Microglia / pathology
  • Neurons / pathology
  • Stress, Physiological*