title: Human C-reactive protein enhances vulnerability of immature rats to hypoxic-ischemic brain damage: a preliminary study.
abstract: In utero exposure to infection or inflammation is a strong and independent predictor of cerebral palsy. Using a rat model of neonatal hypoxic-ischemic (HI) encephalopathy, we investigated the hypothesis that C-reactive protein (CRP), which is not specific for infection, aggravates vulnerability of the immature brain to HI. Seven-day-old rats were divided into human CRP treated and control groups. After injection of each solution, they underwent left common carotid artery ligation and exposure to 8% hypoxia for 40 minutes. Human CRP, rat CRP, and interleukin 6 (IL-6) concentrations in serum were measured by enzyme-linked immunosorbent assay 30 to 60 minutes after injection of each solution. Four days later, microtubule-associated protein 2 (MAP-2) immunostaining was used to examine the brains for neuronal damage. Human CRP treatment significantly reduced the MAP-2 positive area ratio, compared with control group ( P < .05), suggesting that human CRP-enhanced susceptibility to HI-induced brain damage. Mean serum human CRP concentration in the human CRP group was 1823 +/- 520 ng/mL (range: 365-3964 ng/mL). Interleukin 6 concentrations in serum were moderately elevated in both groups, without significant differences, and rat CRP concentrations were within normal range. C-reactive protein makes the immature brain susceptible to HI insult, even if the insult causes little or no injury by itself.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kinugasa-Taniguchi
authors.forename: Takuji
authors.initials: T
authors.lastname: Tomimatsu
authors.forename: Kazuya
authors.initials: K
authors.lastname: Mimura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kanagawa
authors.forename: Koichiro
authors.initials: K
authors.lastname: Shimoya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Murata
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kimura
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002097:C-Reactive Protein / Q000378:metabolism / Q000633:toxicity*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002097:C-Reactive Protein