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Updated: Jan 1, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Why considering sexual differences is necessary when studying encephalopathy of prematurity through rodent models
Bérénice Le Dieu-Lugon1, Nicolas Dupré1, Lou Legouez1
1Normandy Centre for Genomic and Personalized Medicine, UNIROUEN, Inserm U1245 Team 4, Normandy University, Rouen, France.
Insights
Preterm birth can cause brain abnormalities, known as encephalopathy of prematurity, with sex-specific differences. Rodent models reveal mechanisms of this sex-differential vulnerability, aiding in developing targeted interventions.
Area of Science:
- Neuroscience
- Developmental Biology
- Perinatal Medicine
Background:
- Preterm birth is a major risk factor for encephalopathy of prematurity, leading to long-term neurodevelopmental deficits.
- Sex-based differences in prevalence and outcomes of encephalopathy of prematurity are observed, necessitating investigation into underlying biological mechanisms.
- Human studies assessing brain volumes lack mechanistic insights into lesions from very preterm birth.
Purpose of the Study:
- To review rodent models of encephalopathy of prematurity (RMEP) focusing on sex differences in brain vulnerability.
- To elucidate the mechanisms underlying sexual brain dimorphism, particularly in the hippocampus.
- To discuss the relevance of RMEP findings for developing sex-specific interventions for human preterms.
Main Methods:
- Focus on data from mice (P1-P5) and rats (P3) with induced cerebral damage (e.g., hypoxia-ischemia).
- Analysis of brain lesion similarities between rodent models and very preterm human infants.
- Review of studies on sexual brain dimorphism mechanisms and sex-specific vulnerabilities in RMEP.
Main Results:
- Rodent models exhibit brain lesion patterns similar to those in very preterm human infants.
- Mechanisms of sexual brain dimorphism, especially hippocampal, are explored.
- Sex-specific vulnerabilities in RMEP highlight differential hippocampal injury patterns.
Conclusions:
- Rodent models of encephalopathy of prematurity are crucial for understanding sex-differential vulnerability.
- Investigating sex as a biological variable is essential for deciphering injury mechanisms.
- Findings support the need for sex-specific medical interventions for preterm infants.
Abstract:
Preterm birth is a high-risk factor for the development of gray and white matter abnormalities, referred to as "encephalopathy of prematurity," that may lead to life-long motor, cognitive, and behavioral impairments. The prevalence and clinical outcomes of encephalopathy of prematurity differ between sexes, and elucidating the underlying biological basis has become a high-priority challenge. Human studies are often limited to assessment of brain region volumes by MRI, which does not provide much information about the underlying mechanisms of lesions related to very preterm birth. However, models using KO mice or pharmacological manipulations in rodents allow relevant observations to help clarify the mechanisms of injury sustaining sex-differential vulnerability. This review focuses on data obtained from mice aged P1-P5 or rats aged P3 when submitted to cerebral damage such as hypoxia-ischemia, as their brain lesions share similarities with lesion patterns occurring in very preterm human brain, before 32 gestational weeks. We first report data on the mechanisms underlying the development of sexual brain dimorphism in rodent, focusing on the hippocampus. In the second part, we describe sex specificities of rodent models of encephalopathy of prematurity (RMEP), focusing on mechanisms underlying differences in hippocampal vulnerability. Finally, we discuss the relevance of these RMEP. Together, this review highlights the need to systematically search for potential effects of sex when studying the mechanisms underlying deficits in RMEP in order to design effective sex-specific medical interventions in human preterms.
