TY - JOUR
T1 - Argon Inhalation for 24 h After Closed-Head Injury Does not Improve Recovery, Neuroinflammation, or Neurologic Outcome in Mice
AU - Creed, Jennifer
AU - Cantillana-Riquelme, Viviana
AU - Yan, Bai Hui
AU - Ma, Shuang
AU - Chu, Dongmei
AU - Wang, Haichen
AU - Turner, Dennis A.
AU - Laskowitz, Daniel T.
AU - Hoffmann, Ulrike
N1 - Publisher Copyright:
© 2020, Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.
PY - 2021/6
Y1 - 2021/6
N2 - Background/Objective: In recent years, the noble gas argon (Ar) has been extensively studied for its organ protection properties. While mounting in vitro and in vivo evidence indicates that argon provides neuroprotection in ischemic brain injury, its neuroprotective potential in traumatic brain injury (TBI) has not been evaluated in vivo. We tested the hypothesis that prolonged inhalation of 70% or 79% argon for 24 h after closed-head injury (CHI) improves neurologic outcome and overall recovery at 36 days post-injury. We also compared effects of the 30% or 21% residual oxygen on argon’s potential neuroprotective capacity. Methods: Adult male C57/black mice (n = 240) were subjected to closed-head traumatic brain injury, followed by inhalation of 70% argon or nitrogen (30% oxygen), or 79% argon or nitrogen (21% oxygen) for 24 h. Neurologic outcome (rotarod, neuroscore, and Morris water maze) was evaluated for up to 36 days post-injury. Histologic parameters of neurologic degeneration (Fluoro-Jade staining) and inflammation (F4/80 microglia immunostaining) were assessed in subgroups at 24 h and on post-injury day 7. Results: Our CHI protocol consistently resulted in significant brain injury. After argon inhalation for 24 h at either concentration, mice did not show significant improvement with regard to neuroscores, rotarod performance, Morris water maze performance, or overall recovery (body weight), compared to nitrogen controls, up to 36 days. At 7 days post-injury, histologic markers of neurodegeneration and inflammation, particularly in the hippocampus, consistently demonstrated significant injury. Notably, recovery was reduced in mice treated with the higher oxygen concentration (30%) after CHI compared to 21%. Conclusions: Prolonged argon treatment did not improve neurologic outcome, overall recovery (weight), nor markers of neurodegeneration or neuroinflammation after significant CHI compared to nitrogen. While neuroprotective in predominately ischemic injury, argon did not provide protection after TBI in this model, highlighting the crucial importance of assessing argon’s strengths and weaknesses in preclinical models to fully understand its organ protective potential in different pathologies and gas mixtures.
AB - Background/Objective: In recent years, the noble gas argon (Ar) has been extensively studied for its organ protection properties. While mounting in vitro and in vivo evidence indicates that argon provides neuroprotection in ischemic brain injury, its neuroprotective potential in traumatic brain injury (TBI) has not been evaluated in vivo. We tested the hypothesis that prolonged inhalation of 70% or 79% argon for 24 h after closed-head injury (CHI) improves neurologic outcome and overall recovery at 36 days post-injury. We also compared effects of the 30% or 21% residual oxygen on argon’s potential neuroprotective capacity. Methods: Adult male C57/black mice (n = 240) were subjected to closed-head traumatic brain injury, followed by inhalation of 70% argon or nitrogen (30% oxygen), or 79% argon or nitrogen (21% oxygen) for 24 h. Neurologic outcome (rotarod, neuroscore, and Morris water maze) was evaluated for up to 36 days post-injury. Histologic parameters of neurologic degeneration (Fluoro-Jade staining) and inflammation (F4/80 microglia immunostaining) were assessed in subgroups at 24 h and on post-injury day 7. Results: Our CHI protocol consistently resulted in significant brain injury. After argon inhalation for 24 h at either concentration, mice did not show significant improvement with regard to neuroscores, rotarod performance, Morris water maze performance, or overall recovery (body weight), compared to nitrogen controls, up to 36 days. At 7 days post-injury, histologic markers of neurodegeneration and inflammation, particularly in the hippocampus, consistently demonstrated significant injury. Notably, recovery was reduced in mice treated with the higher oxygen concentration (30%) after CHI compared to 21%. Conclusions: Prolonged argon treatment did not improve neurologic outcome, overall recovery (weight), nor markers of neurodegeneration or neuroinflammation after significant CHI compared to nitrogen. While neuroprotective in predominately ischemic injury, argon did not provide protection after TBI in this model, highlighting the crucial importance of assessing argon’s strengths and weaknesses in preclinical models to fully understand its organ protective potential in different pathologies and gas mixtures.
KW - Argon
KW - Mice
KW - Neuroprotection
KW - Noble gases
KW - TBI
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UR - http://www.scopus.com/inward/citedby.url?scp=85091274771&partnerID=8YFLogxK
U2 - 10.1007/s12028-020-01104-0
DO - 10.1007/s12028-020-01104-0
M3 - Article
C2 - 32959200
AN - SCOPUS:85091274771
SN - 1541-6933
VL - 34
SP - 833
EP - 843
JO - Neurocritical Care
JF - Neurocritical Care
IS - 3
ER -