Related Experiment Video
Updated: Jun 15, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Human C-reactive protein enhances vulnerability of immature rats to hypoxic-ischemic brain damage: a preliminary
Yukiko Kinugasa-Taniguchi1, Takuji Tomimatsu, Kazuya Mimura
1Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Insights
C-reactive protein (CRP) exposure increases the immature brain's susceptibility to hypoxic-ischemic (HI) injury. This finding suggests CRP may worsen brain damage in newborns following birth complications.
Area of Science:
- Neuroscience
- Immunology
- Neonatal Research
Background:
- In utero infection/inflammation predicts cerebral palsy.
- C-reactive protein (CRP) is a non-specific marker of inflammation.
Purpose of the Study:
- Investigate if CRP exacerbates neonatal brain vulnerability to hypoxic-ischemic (HI) insult.
- Determine CRP's role in neonatal brain injury.
Main Methods:
- Used a rat model of neonatal HI encephalopathy.
- Administered human CRP or control solution to 7-day-old rats.
- Assessed neuronal damage via MAP-2 immunostaining 4 days post-HI.
Main Results:
- Human CRP treatment significantly increased neuronal damage (reduced MAP-2 positive area) post-HI (P < .05).
- Serum human CRP levels averaged 1823 ng/mL in the treated group.
- Interleukin-6 (IL-6) levels were similarly elevated in both groups; rat CRP remained normal.
Conclusions:
- C-reactive protein (CRP) enhances susceptibility of the immature brain to hypoxic-ischemic (HI) injury.
- CRP may contribute to brain damage in newborns experiencing perinatal insults, independent of infection.
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.
