Temporal evolution of heme oxygenase-1 expression in reactive astrocytes and microglia in response to traumatic brain injury

Alexander Morita, Amandine Jullienne, Arjang Salehi, Mary Hamer, Emon Javadi, Yasir Alsarraj, Jiping Tang, John H. Zhang, William J. Pearce, André Obenaus

Research output: Contribution to journalArticlepeer-review

Abstract

Heme oxygenase-1 (HO-1) is an inducible enzyme that catabolizes heme into biliverdin (which is converted to bilirubin), carbon monoxide, and free iron. HO-1 and its downstream molecules have antioxidant and anti-inflammatory functions, making the effects of HO-1 difficult to predict. It is unknown if HO-1 expression has neuroprotective or neurodegenerative sequelae after traumatic brain injury (TBI). In adult male mice, we quantitatively investigated HO-1 expression in reactive astrocytes and microglia in a controlled cortical impact (CCI) model of TBI at 1, 7, 14, and 30 days post-injury (dpi). Immunoglobulin G (IgG) staining for blood-brain barrier (BBB) permeability was significantly increased at 1 and 7 dpi in TBI mice compared to controls. HO-1 expression in astrocytes was significantly increased acutely and sub-acutely (1, 7, 14 dpi) compared to controls. Significantly elevated expression of HO-1 in microglia was only observed at 14 and 30 dpi relative to controls. HO-1 expression remained elevated at 30 dpi following TBI relative to controls. This study for the first time demonstrates that HO-1 is highly expressed in perilesional tissues after TBI, but primarily in cells that contribute to the neuroinflammatory response. Modulating HO-1 expression may provide a path to therapeutic intervention by enhancing the neuroprotective aspects of HO-1. Summary statement: Heme oxygenase-1 expression after traumatic brain injury in adult male mice occurs first in reactive astrocytes followed by dramatic increases in microglia adjacent to the injury site.

Original languageEnglish
Pages (from-to)65-74
Number of pages10
JournalBrain Hemorrhages
Volume1
Issue number1
DOIs
StatePublished - Mar 2020

ASJC Scopus Subject Areas

  • Surgery
  • Neuroscience (miscellaneous)
  • Neurology
  • Clinical Neurology

Keywords

  • Astrocytes
  • Heme oxygenase-1
  • Microglia
  • Traumatic brain injury

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