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Updated: Sep 7, 2025
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Multi-Hit White Matter Injury-Induced Cerebral Palsy Model Established by Perinatal Lipopolysaccharide Injection
Le Liu1,2, Liwei Fang1, Boyang Duan3
1Department of Pediatrics, Pediatric Neurorehabilitation Center, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Insights
Researchers developed a multi-hit rat model for cerebral palsy (CP) by inducing white matter injury (WMI). This model shows microglial activation is closely linked to CP development, suggesting microglia as a potential therapeutic target.
Area of Science:
- Neuroscience
- Developmental Biology
- Pathology
Background:
- Cerebral palsy (CP) is a disorder of movement and posture caused by brain injury.
- White matter injury (WMI) is a primary cause of CP, particularly in preterm infants.
Purpose of the Study:
- To establish a "multi-hit" rat model mimicking human WMI in CP.
- To investigate the role of microglial activation in WMI-induced CP.
Main Methods:
- A "multi-hit" rat model was created to induce WMI.
- Histological and electron microscopy analyses were performed.
- Microglial activation markers (IBA1, CD11c, Arg1) were assessed.
Main Results:
- The WMI model exhibited CP-like symptoms (limb paresis, incoordination) and histological changes (neuronal loss, inflammation).
- Electron microscopy revealed neuronal apoptosis, glial activation, and delayed myelination.
- Microglial activation showed a transition from M1 to M2 phenotype following LPS/infection stimulation.
Conclusions:
- The established "multi-hit" WMI rat model effectively mimics human CP.
- Microglial activation is significantly correlated with CP development.
- Microglia represent a potential therapeutic target for CP.
Abstract:
Cerebral palsy (CP) is a group of permanent, but not unchanging, disorders of movement and/or posture and motor function. Since the major brain injury associated with CP is white matter injury (WMI), especially, in preterm infants, we established a "multi-hit" rat model to mimic human WMI in symptomatology and at a histological level. In our WMI model, pups suffering from limb paresis, incoordination, and direction difficulties fit the performance of CP. Histologically, they present with fewer neural cells, inordinate fibers, and more inflammatory cell infiltration, compared to the control group. From the electron microscopy results, we spotted neuronal apoptosis, glial activation, and myelination delay. Besides, the abundant appearance of IBA1-labeled microglia also implied that microglia play a role during neuronal cell injury. After activation, microglia shift between the pro-inflammatory M1 type and the anti-inflammatory M2 type. The results showed that LPS/infection stimulated IBA1 + (marked activated microglia) expression, downregulated CD11c + (marked M1 phenotype), and upregulated Arg 1 + (marked M2 phenotype) protein expression. It indicated an M1 to M2 transition after multiple infections. In summary, we established a "multi-hit" WMI-induced CP rat model and demonstrated that the microglial activation correlates tightly with CP formation, which may become a potential target for future studies.
