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Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice.
J Neurotrauma 2015; 32(2):127-38JN

Abstract

Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15-30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1 d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1β, tumor necrosis factor α) in enriched microglia/macrophages 1 d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1β and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1-7 d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7 d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications.

Authors+Show Affiliations

1 Department of Neuroscience, Ohio State University , Columbus, Ohio.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25070744

Citation

Fenn, Ashley M., et al. "Methylene Blue Attenuates Traumatic Brain Injury-associated Neuroinflammation and Acute Depressive-like Behavior in Mice." Journal of Neurotrauma, vol. 32, no. 2, 2015, pp. 127-38.
Fenn AM, Skendelas JP, Moussa DN, et al. Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice. J Neurotrauma. 2015;32(2):127-38.
Fenn, A. M., Skendelas, J. P., Moussa, D. N., Muccigrosso, M. M., Popovich, P. G., Lifshitz, J., ... Godbout, J. P. (2015). Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice. Journal of Neurotrauma, 32(2), pp. 127-38. doi:10.1089/neu.2014.3514.
Fenn AM, et al. Methylene Blue Attenuates Traumatic Brain Injury-associated Neuroinflammation and Acute Depressive-like Behavior in Mice. J Neurotrauma. 2015 Jan 15;32(2):127-38. PubMed PMID: 25070744.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Methylene blue attenuates traumatic brain injury-associated neuroinflammation and acute depressive-like behavior in mice. AU - Fenn,Ashley M, AU - Skendelas,John P, AU - Moussa,Daniel N, AU - Muccigrosso,Megan M, AU - Popovich,Phillip G, AU - Lifshitz,Jonathan, AU - Eiferman,Daniel S, AU - Godbout,Jonathan P, Y1 - 2014/11/13/ PY - 2014/7/30/entrez PY - 2014/7/30/pubmed PY - 2015/9/12/medline KW - cytokines KW - fluid percussion injury KW - intervention KW - microglia KW - recovery SP - 127 EP - 38 JF - Journal of neurotrauma JO - J. Neurotrauma VL - 32 IS - 2 N2 - Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15-30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1 d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1β, tumor necrosis factor α) in enriched microglia/macrophages 1 d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1β and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1-7 d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7 d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications. SN - 1557-9042 UR - https://www.unboundmedicine.com/medline/citation/25070744/Methylene_blue_attenuates_traumatic_brain_injury_associated_neuroinflammation_and_acute_depressive_like_behavior_in_mice_ L2 - https://www.liebertpub.com/doi/full/10.1089/neu.2014.3514?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -