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Updated: May 3, 2026

The Hypoxic Ischemic Encephalopathy Model of Perinatal Ischemia
Published on: November 19, 2008
Treatment with carnosine reduces hypoxia-ischemia brain damage in a neonatal rat model
Huizhen Zhang1, Shang Guo2, Linlin Zhang1
1Department of Clinical Laboratory, The Third Affiliated Hospital of Zhengzhou University, Kangfuqian Street 7, Zhenzhou 450052, China.
Insights
Carnosine treatment after neonatal hypoxia-ischemia brain damage (HIBD) reduces brain injury and improves cognitive function. This study shows carnosine
Area of Science:
- Neuroscience
- Neonatal Research
- Biochemistry
Background:
- Perinatal hypoxia-ischemia brain damage (HIBD) is a leading cause of neonatal mortality and morbidity with no effective treatments.
- Carnosine demonstrates neuroprotective effects in adult brain injury models.
- Previous research indicated carnosine pretreatment protects against HIBD in neonatal rats.
Purpose of the Study:
- To investigate the neuroprotective effects of carnosine treatment administered *after* HIBD in a neonatal rat model.
- To evaluate carnosine's impact on biochemical markers of brain injury and cognitive function.
Main Methods:
- Neonatal rats (postnatal days 7-9) underwent induced hypoxia-ischemia (HI).
- Carnosine (250mg/kg) was administered intraperitoneally at 0, 24, and 48 hours post-HI.
- Biochemical markers (oxidative stress, apoptosis) were assessed at 72 hours post-HI.
- Cognitive function was evaluated using the Morris water maze test on postnatal days 28-33.
Main Results:
- Carnosine treatment significantly reduced 8-iso-prostaglandin F2α levels in brain tissue.
- A decrease in TUNEL-positive cells and mitochondria caspase-3 expression was observed in carnosine-treated rats.
- Carnosine administration improved cognitive performance in rats affected by HIBD.
Conclusions:
- Post-HIBD carnosine treatment effectively mitigates brain injury markers.
- Carnosine administration enhances cognitive function recovery following neonatal HIBD.
- Carnosine presents a promising therapeutic candidate for treating HIBD.
Abstract:
Perinatal hypoxia-ischemia brain damage (HIBD) is a major cause of mortality and morbidity in neonates, and there is currently no effective therapy for HIBD. Carnosine plays a neuroprotective role in adult brain damage. We have previously demonstrated that carnosine pretreatment protects against HIBD in a neonatal rat model. Therefore, we hypothesized that treatment with carnosine would also have neuroprotective effects. Hypoxia-ischemia was induced in rats on postnatal days 7-9 (P7-9). Carnosine was administered intraperitoneally at a dose of 250mg/kg at 0h, 24h, and 48h after hypoxia-ischemia was induced. The biochemical markers of oxidative stress and apoptosis were evaluated at 72h after hypoxia-ischemia was induced, Brain learning and memory function performance were observed using the Morris water maze test on postnatal days 28-33 (P28-33). Treatment with carnosine post-HIBD significantly reduced the concentration of 8-iso-prostaglandinF2alpha in brain tissue and decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in the hippocampus CA1 region and cortex as well as the mitochondria caspase-3 protein expression. Furthermore, carnosine also improved the cognitive function of P28-33 rats, whose cognitive function decline was due to HIBD. These results demonstrate that carnosine treatment after HIBD can reduce the brain injury, improving brain function. Carnosine could be an attractive candidate for treating HIBD.

