Overexpression of interleukin-1 receptor antagonist reduces brain edema induced by intracerebral hemorrhage and thrombin
Recent studies indicate that inflammatory reaction occurs around hematoma after intracerebral hemorrhage (ICH). In this study the authors examine the hypothesis that overexpression of IL-1ra in the brain attenuate brain edema formation after ICH .
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© Springer-Verlag 2003
Overexpression of interleukin-l receptor antagonist reduces brain edema induced by intracerebral hemorrhage and thrombin T. Masada ', Y. Hua 2 , G. Xi2 , G.-Y. Yang', J. T. Hoff 2 , R. F. Keep", and S. Nagao ' Department of Neurological Surgery, Kagawa Medical University, Japan Department of Surgery (Neurosurgery), University of Michigan, Ann Arbor, Michigan 3 Department of Physiology, University of Michigan , Ann Arbor, Michigan 1
2
Summary Recent studies indicate that inflammatory reaction occurs around hematoma after intracerebral hemorrhage (lCH). In this study the authors examine the hypothesis that overexpression of IL-l ra in the brain attenuate brain edema formation after ICH . Adenoviruses expressing IL-lra (Ad.RSVIL-lra) or LacZ (Ad.RSVLacZ) or saline were injected into the lateral ventricle. On the fifth day after virus injection, 100 fll of autologous blood or 5 U thrombin was infused into the right basal ganglia . Rats with ICH were killed 24 or 72 hours later for measurement of brain water content. Thrombin-treated rats were killed 24 hours later for edema measurements and an assessment of polymorphonuclear leukocyte (PMNL) infiltration by myeloperoxidase (MPO) assay. Compared with control groups , Ad.RSVIL-lra treated rats had less brain edema formation in the ipsilateral basal ganglia 3 days after ICH (81.5 ± 0.3% compared with 83.4 ± 0.4% and 83.3 ± 0.5% in control animals). Ad.RSVIL-lra treated rats had also less brain edema following thrombin injection. The reduction of brain edema induced by thrombin was involved in the reduction ofPMNL infiltration in basal ganglia, as assessed by MPO assay. Adenovirus-mediated overexpression of IL-I ra attenuated brain edema formation following lCH, perhaps by reduction ofthrombininduced brain inflammation . Keywords: Intracerebral hemorrhage; brain edema; thrombin; interleukin-l receptor antagonist; inflammation ; rat.
erotic factor-a, which are involved in the migration of white blood cells from blood to brain . Infiltration of inflammatory cells in the brain and release of cytokines such as IL-I B induce tissue injury and brain edema formation [3]. The interleukin-I receptor antagonist (IL-lra) inhibits several actions of IL-I, and administration of IL-I ra reduces ischemic and traumatic brain injuries [10]. Adenovirus-mediated overexpression of IL-lra also attenuates ischemic brain injury [11] . The effect of IL-Ira on ICH has not been studied. In this study, we examine whether adenovirusmediated overexpression of IL-Ira can reduce the brain edema following ICH or thrombin instillation into the basal ganglia, and whether IL-Ira overexpression reduces the thrombin-induced inflammatory response.
Materials and methods Animal preparation
Introduction Brain edema induced by intracerebral hemorrhage (ICH) elevates intracranial pressure and causes brain herniation. Preventing the accumulation of edema is important for the management of ICH . One of the mechanisms to produce brain edema after ICH is thrombin, which induces a variety of
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