title: Posttraumatic therapeutic hypothermia alters microglial and macrophage polarization toward a beneficial phenotype.
abstract: Posttraumatic inflammatory processes contribute to pathological and reparative processes observed after traumatic brain injury (TBI). Recent findings have emphasized that these divergent effects result from subsets of proinflammatory (M1) or anti-inflammatory (M2) microglia and macrophages. Therapeutic hypothermia has been tested in preclinical and clinical models of TBI to limit secondary injury mechanisms including proinflammatory processes. This study evaluated the effects of posttraumatic hypothermia (PTH) on phenotype patterns of microglia/macrophages. Sprague-Dawley rats underwent moderate fluid percussion brain injury with normothermia (37℃) or hypothermia (33℃). Cortical and hippocampal regions were analyzed using flow cytometry and reverse transcription-polymerase chain reaction (RT-PCR) at several periods after injury. Compared to normothermia, PTH attenuated infiltrating cortical macrophages positive for CD11b+and CD45high. At 24 h, the ratio of iNOS+(M1) to arginase+(M2) cells after hypothermia showed a decrease compared to normothermia. RT-PCR of M1-associated genes including iNOS and IL-1β was significantly reduced with hypothermia while M2-associated genes including arginase and CD163 were significantly increased compared to normothermic conditions. The injury-induced increased expression of the chemokine Ccl2 was also reduced with PTH. These studies provide a link between temperature-sensitive alterations in macrophage/microglia activation and polarization toward a M2 phenotype that could be permissive for cell survival and repair.
authors.affiliation: Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: Jessie S
authors.initials: JS
authors.lastname: Truettner
authors.affiliation: Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: Helen M
authors.initials: HM
authors.lastname: Bramlett
authors.affiliation: Department of Neurological Surgery, The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, USA.
authors.forename: W Dalton
authors.initials: WD
authors.lastname: Dietrich
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016207:Cytokines / Q000276:immunology; D005434:Flow Cytometry; D007036:Hypothermia, Induced; D008262:Macrophage Activation / Q000276:immunology / Q000502:physiology; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D008297:Male; D017628:Microglia / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016207:Cytokines
keywords: Cytokines; inflammation; macrophages; microglial; traumatic brain injury