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Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Offspring of rats with cerebral hypoxia-ischemia manifest cognitive dysfunction in learning and memory abilities
Lu-Lu Xue1, Fang Wang2, Rui-Ze Niu3
1Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province; Institute of Neuroscience, Kunming Medical University, Kunming, Yunnan Province, China.
Insights
Neonatal hypoxic-ischemic encephalopathy in parent rats led to cognitive impairments in their offspring, affecting learning and memory. This suggests potential intergenerational transmission of neurodevelopmental deficits.
Area of Science:
- Neuroscience
- Developmental Biology
- Pediatrics
Background:
- Neonatal hypoxic-ischemic encephalopathy (HIE) causes significant neurodevelopmental issues in affected children.
- The potential for these HIE-induced neurodevelopmental problems to be transmitted across generations is not well understood.
Purpose of the Study:
- To investigate whether neurodevelopmental deficits resulting from neonatal hypoxic-ischemic encephalopathy in parent rats can be inherited by their offspring.
- To assess the cognitive function and learning/memory capabilities of offspring from HIE-affected parent rats.
Main Methods:
- Established a neonatal rat model of hypoxic-ischemic encephalopathy (HIE) by ligating the carotid artery and inducing hypoxia in 7-day-old pups.
- Propagated the HIE model rats and evaluated the learning and memory functions of their offspring using behavioral tests, including escape latency and platform crossings.
- Utilized magnetic resonance imaging (MRI) to assess gross brain structure in the offspring.
Main Results:
- HIE induction in neonatal rats resulted in significant pathological brain damage, cerebral atrophy, and increased Zea-Longa scores.
- Offspring of HIE-affected rats exhibited longer escape latencies and fewer platform crossings, indicating impaired learning and memory.
- MRI revealed no gross structural abnormalities in the brains of the offspring.
Conclusions:
- Neonatal hypoxic-ischemic encephalopathy in parent rats can lead to cognitive impairments, specifically in learning and memory, in their offspring.
- These findings suggest a potential intergenerational effect of HIE on neurodevelopment, even without overt structural brain changes in the offspring.
- Further research is warranted to elucidate the mechanisms underlying this intergenerational transmission of cognitive deficits.
Abstract:
Neonatal hypoxic-ischemic encephalopathy is a serious neurological disease, often resulting in long-term neurodevelopmental disorders among surviving children. However, whether these neurodevelopmental issues can be passed to offspring remains unclear. The right common carotid artery of 7-day-old parental-generation rats was subjected to permanent ligation using a vessel electrocoagulator. Neonatal hypoxic-ischemic rat models were established by subjecting the rats to 8% O2-92% N2 for 2 hours. The results showed that 24 hours after hypoxia and ischemia, pathological damage, cerebral atrophy, liquefaction, and impairment were found, and Zea-Longa scores were significantly increased. The parental-generation rats were propagated at 3 months old, and offspring were obtained. No changes in the overall brain structures of these offspring rats were identified by magnetic resonance imaging. However, the escape latency was longer and the number of platform crossings was reduced among these offspring compared with normal rats. These results indicated that the offspring of hypoxic-ischemic encephalopathy model rats displayed cognitive impairments in learning and memory. This study was approved by the Animal Care & Welfare Committee of Kunming Medical University, China in 2018 (approval No. kmmu2019072).
