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Human C-Reactive Protein Enhances Vulnerability of Immature Rats to Hypoxic—Ischemic Brain Damage: A Preliminary Study

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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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2, Yamada-oka, Suita, 565-0871, Osaka, Japan

    Yukiko Kinugasa-Taniguchi MD, Takuji Tomimatsu MD, Kazuya Mimura MD, Takeshi Kanagawa MD & Tadashi Kimura MD, PhD

  2. Department of Obstetrics and Gynecology, Kawasaki Medical University, Kurashiki, Okayama, Japan

    Koichiro Shimoya MD, PhD

  3. Seichokai, Sakai City, Osaka, Japan

    Yuji Murata MD, PhD

Authors
  1. Yukiko Kinugasa-Taniguchi MD
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  2. Takuji Tomimatsu MD
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  3. Kazuya Mimura MD
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  4. Takeshi Kanagawa MD
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  5. Koichiro Shimoya MD, PhD
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  6. Yuji Murata MD, PhD
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  7. Tadashi Kimura MD, PhD
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Correspondence to Takuji Tomimatsu MD.

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Kinugasa-Taniguchi, Y., Tomimatsu, T., Mimura, K. et al. Human C-Reactive Protein Enhances Vulnerability of Immature Rats to Hypoxic—Ischemic Brain Damage: A Preliminary Study. Reprod. Sci. 17, 419–425 (2010). https://doi.org/10.1177/1933719110361379

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  • DOI: https://doi.org/10.1177/1933719110361379

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