The NADPH oxidase NOX2 mediates loss of parvalbumin interneurons in traumatic brain injury: human autoptic immunohistochemical evidence

Sci Rep. 2017 Aug 18;7(1):8752. doi: 10.1038/s41598-017-09202-4.

Abstract

Pharmacological interventions for traumatic brain injury (TBI) are limited. Together with parvalbumin (PV) loss, increased production of reactive oxygen species (ROS) by the NADPH oxidase NOX enzymes represents a key step in TBI. Here, we investigated the contribution of NOX2-derived oxidative stress to the loss of PV immunoreactivity associated to TBI, performing immunohistochemistry for NOX2, 8-hydroxy-2'-deoxyguanosine (8OHdG) and PV on post mortem brain samples of subjects died following TBI, subjects died from spontaneous intracerebral hemorrhage (SICH) and controls (CTRL). We detected an increased NOX2 expression and 8OHdG immunoreactivity in subjects died from TBI with respect to CTRL and SICH. NOX2 increase was mainly observed in GABAergic PV-positive interneurons, with a minor presence in microglia. No significant differences in other NADPH oxidase isoforms (NOX1 and NOX4) were detected among experimental groups. NOX2-derived oxidative stress elevation appeared a specific TBI-induced phenomenon, as no alterations in the nitrosative pathway were detected. Our results suggest that NOX2-derived oxidative stress might play a crucial role in the TBI-induced loss of PV-positive interneurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Brain Injuries, Traumatic / etiology
  • Brain Injuries, Traumatic / metabolism*
  • Brain Injuries, Traumatic / pathology
  • Cell Count
  • Deoxyguanosine / analogs & derivatives
  • Humans
  • Immunohistochemistry
  • Interneurons / metabolism*
  • Male
  • NADPH Oxidase 2 / metabolism*
  • Oxidation-Reduction
  • Oxidative Stress
  • Parvalbumins / metabolism*
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Parvalbumins
  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • 8-Hydroxy-2'-Deoxyguanosine
  • NADPH Oxidase 2
  • Deoxyguanosine