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

• Published in: Brain hemorrhages 2020-03, Vol.1 (1), p.65-74
• Main Authors: Morita, Alexander, Jullienne, Amandine, Salehi, Arjang, Hamer, Mary, Javadi, Emon, Alsarraj, Yasir, Tang, Jiping, Zhang, John H., Pearce, William J., Obenaus, André
• Format: Article
• Language: English
• Subjects: Astrocytes; Heme oxygenase-1; Microglia; Traumatic brain injury
• ISSN: 2589-238X; 2589-238X
• DOI: 10.1016/j.hest.2020.01.002

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. 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.