Dataset Information

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.

Methodology/principal findings

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/significance

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.

SUBMITTER: Winerdal M

PROVIDER: S-EPMC3342175 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

Long lasting local and systemic inflammation after cerebral hypoxic ischemia in newborn mice.

Winerdal Max M Winerdal Malin Elisabeth ME Kinn Johan J Urmaliya Vijay V Winqvist Ola O Adén Ulrika U

PloS one 20120502 5

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>We developed a multiplex flow cytometry based method combined with immunohistochemistry to investigate cellular i ...[more]

PMID: 22567156

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Project description:BackgroundTrauma is the leading cause of death and disability worldwide, especially in the young population. Cardiac injuries are an independent predictor for a poor overall outcome after trauma. The aim of the present study was to analyze systemic inflammation as well as local cardiac inflammation after experimental limb-, neuro- and combined trauma in mice.MethodsMale C57BL/6 mice received either a closed tibia fracture (Fx), isolated traumatic brain injury (TBI) or a combination of both (Fx + TBI). Control animals underwent sham procedure. After 6 and 24 h, systemic levels of inflammatory mediators were analyzed, respectively. Locally, cardiac inflammation and cardiac structural alterations were investigated in left ventricular tissue of mice 6 and 24 h after trauma.ResultsMice showed enhanced systemic inflammation after combined trauma, which was manifested by increased levels of KC, MCP-1 and G-CSF. Locally, mice exhibited increased expression of inflammatory cytokines (IL-1β, TNF) in heart tissue, which was probably mediated via toll-like receptor (TLR) signaling. Furthermore, mice demonstrated a redistribution of connexin 43 in cardiac tissue, which appeared predominantly after combined trauma. Besides inflammation and structural cardiac alterations, expression of glucose transporter 4 (GLUT4) mRNA was increased in the heart early after TBI and after combination of TBI and limb fracture, indicating a modification of energy metabolism. Early after combination of TBI and tibia fracture, nitrosative stress was increased, manifested by elevation of nitrotyrosine in cardiac tissue. Finally, mice showed a trend of increased systemic levels of cardiac troponin I and heart-fatty acid binding protein (HFABP) after combined trauma, which was associated with a significant decrease of troponin I and HFABP mRNA expression in cardiac tissue after TBI and combination of TBI and limb fracture.ConclusionMice exhibited early cardiac alterations as well as alterations in cardiac glucose transporter expression, indicating a modification of energy metabolism, which might be linked to increased systemic- and local cardiac inflammation after limb-, neuro- and combined trauma. These cardiac alterations might predispose individuals for secondary cardiac damage after trauma that might compromise cardiac function after TBI and long bone fracture.Translational potential statementInjuries to the head and extremities frequently occur after severe trauma. In our study, we analyzed the effects of closed tibia fracture, isolated TBI, and the combination of both injuries with regard to the development of post-traumatic secondary cardiac injuries.

Dataset Information

Long lasting local and systemic inflammation after cerebral hypoxic ischemia in newborn mice.

Background

Methodology/principal findings

Conclusions/significance

Publications

Long lasting local and systemic inflammation after cerebral hypoxic ischemia in newborn mice.

Similar Datasets

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