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Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury.
ASN Neuro 2015 Nov-Dec; 7(6)AN

Abstract

We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1 ml/kg) was administered intraperitonially at 5 min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti-inflammatory marker CD206 in Iba1(+) microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32(+) microglia or macrophages, but an increased CD206(+) phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1(+) microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1(+) microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain-enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic potential to ameliorate TBI-induced cellular pathology.

Authors+Show Affiliations

Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.Department of Neurology, the Second Hospital of Dalian Medical University, Dalian, China.Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA.Department of Neurosurgery, Brain Trauma Research Center, University of Pittsburgh, Pittsburgh, PA, USA Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA, USA.Department of Neurosurgery, Brain Trauma Research Center, University of Pittsburgh, Pittsburgh, PA, USA Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA, USA.Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA Geriatric Research, Education and Clinical Center, Veterans Affairs Pittsburgh Health Care System, Pittsburgh, PA, USA sund@upmc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

26685193

Citation

Harvey, Lloyd D., et al. "Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury." ASN Neuro, vol. 7, no. 6, 2015.
Harvey LD, Yin Y, Attarwala IY, et al. Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury. ASN Neuro. 2015;7(6).
Harvey, L. D., Yin, Y., Attarwala, I. Y., Begum, G., Deng, J., Yan, H. Q., ... Sun, D. (2015). Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury. ASN Neuro, 7(6), doi:10.1177/1759091415618969.
Harvey LD, et al. Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury. ASN Neuro. 2015;7(6) PubMed PMID: 26685193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury. AU - Harvey,Lloyd D, AU - Yin,Yan, AU - Attarwala,Insiya Y, AU - Begum,Gulnaz, AU - Deng,Julia, AU - Yan,Hong Q, AU - Dixon,C Edward, AU - Sun,Dandan, Y1 - 2015/12/18/ PY - 2015/12/20/entrez PY - 2015/12/20/pubmed PY - 2016/8/16/medline KW - cortical contusion injury KW - docosahexaenoic acid KW - microglial polarization KW - neuroinflammation KW - nuclear factor kappa-light-chain-enhancer of activated B cells KW - secondary injury JF - ASN neuro JO - ASN Neuro VL - 7 IS - 6 N2 - We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1 ml/kg) was administered intraperitonially at 5 min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti-inflammatory marker CD206 in Iba1(+) microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32(+) microglia or macrophages, but an increased CD206(+) phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1(+) microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1(+) microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain-enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic potential to ameliorate TBI-induced cellular pathology. SN - 1759-0914 UR - https://www.unboundmedicine.com/medline/citation/26685193/Administration_of_DHA_Reduces_Endoplasmic_Reticulum_Stress_Associated_Inflammation_and_Alters_Microglial_or_Macrophage_Activation_in_Traumatic_Brain_Injury_ L2 - http://journals.sagepub.com/doi/full/10.1177/1759091415618969?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -