title: Long lasting local and systemic inflammation after cerebral hypoxic ischemia in newborn mice.
abstract: BACKGROUND
  Hypoxic ischemia (HI) is an important cause of neonatal brain injury and subsequent inflammation affects neurological outcome. In this study we performed investigations of systemic and local activation states of inflammatory cells from innate and adaptive immunity at different time points after neonatal HI brain injury in mice.
  
  
  RESULTS
  We developed a multiplex flow cytometry based method combined with immunohistochemistry to investigate cellular immune responses in the brain 24 h to 7 months after HI brain injury. In addition, functional studies of ex vivo splenocytes after cerebral hypoxic ischemia were performed. Both central and peripheral activation of CD11b(+) and CD11c(+) antigen presenting cells were seen with expression of the costimulatory molecule CD86 and MHC-II, indicating active antigen presentation in the damaged hemisphere and in the spleen. After one week, naïve CD45rb(+) T-lymphocytes were demonstrated in the damaged brain hemisphere. In a second phase after three months, pronounced activation of CD45rb(-) T-lymphocytes expressing CD69 and CD25 was seen in the damaged hemisphere. Brain homogenate induced proliferation in splenocytes after HI but not in controls.
  
  
  CONCLUSIONS
  Our findings demonstrate activation of both local and systemic immune responses months after hypoxic ischemic neonatal brain injury. The long term immune activation observed is of general importance for future studies of the inflammatory response after brain injury as most previous studies have focused on the first few weeks after damage, while the effects of the late inflammation phase may be missed. Furthermore, the self-reactive component raises the question if there is a correlation with development of autoimmune brain disease later in life.
authors.affiliation: Department of Woman and Child Health, Karolinska Institutet, Stockholm, Sweden. max.winerdal@ki.se
authors.forename: Max
authors.initials: M
authors.lastname: Winerdal
authors.forename: Malin Elisabeth
authors.initials: ME
authors.lastname: Winerdal
authors.forename: Johan
authors.initials: J
authors.lastname: Kinn
authors.forename: Vijay
authors.initials: V
authors.lastname: Urmaliya
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
authors.forename: Ulrika
authors.initials: U
authors.lastname: Adén
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002545:Brain Ischemia / Q000276:immunology*; D005434:Flow Cytometry; D020925:Hypoxia-Ischemia, Brain / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D051379:Mice