Heme oxygenase-1 (HO-1) is an inducible enzyme that catabolizes heme into biliverdin (which is converted to bilirubin), carbon monoxide, and free iron. Free iron, particularly Fe2+, is known to have cytotoxic effects, largely via the Fenton reaction. Alternatively, bilirubin and carbon monoxide have been shown to have antioxidant and anti-inflammatory functions, respectively, making the effects of HO-1 difficult to predict. In intracerebral hemorrhage, enhanced HO-1 expression has been reported to be beneficial. However, it is unknown if HO-1 expression has neuroprotective or neurodegenerative sequelae after traumatic brain injury (TBI). In our male mouse study, 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 as a measure of blood-brain barrier (BBB) permeability was significantly higher in 1 and 7dpi mice compared to controls, indicating BBB disruption early after TBI. HO-1 expression in astrocytes was significantly increased acutely and subacutely (1, 7, 14dpi) compared to controls.

In contrast, significantly elevated expression of HO-1 in microglia was only observed at the chronic 14 and 30dpi time points relative to controls. This study demonstrates that HO-1 is highly expressed after TBI, but primarily in cells that contribute to the neuroinflammatory response and modulating this expression may provide a path to therapeutic intervention.