TY - JOUR
T1 - Temporal evolution of heme oxygenase-1 expression in reactive astrocytes and microglia in response to traumatic brain injury
AU - Morita, Alexander
AU - Jullienne, Amandine
AU - Salehi, Arjang
AU - Hamer, Mary
AU - Javadi, Emon
AU - Alsarraj, Yasir
AU - Tang, Jiping
AU - Zhang, John H.
AU - Pearce, William J.
AU - Obenaus, André
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Heme oxygenase-1
KW - Microglia
KW - Traumatic brain injury
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UR - https://www.mendeley.com/catalogue/6b9bcb9d-f5c8-30b9-b540-98d7e48caa0f/
U2 - 10.1016/j.hest.2020.01.002
DO - 10.1016/j.hest.2020.01.002
M3 - Article
SN - 2589-238X
VL - 1
SP - 65
EP - 74
JO - Brain Hemorrhages
JF - Brain Hemorrhages
IS - 1
ER -