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.

ObjectiveWe performed a meta-analysis to investigate the relationship between blood tumor necrosis factor-alpha (TNF-α) levels and the risk of cerebral palsy (CP) in children.MethodsPubMed, Web of Science, Cochrane Library and Ovid databases were searched from the date of database inception to 26 April 2022. Data were extracted and pooled from observational studies related to TNF-α and the risk of CP in children. Quality was assessed using the Newcastle-Ottawa Scale. We used the inverse variance method with a random-effects model to estimate the odds ratios with 95% confidence intervals (CIs), and stratified analyses and sensitivity analysis were utilized to analyse heterogeneity.ResultsNine studies with 1,117 cases and 3,563 controls were included in our meta-analysis. The quality of the literature was good, and no publication bias was noted. According to the random-effects model, blood TNF-α levels were associated with the risk of CP (OR 1.82; 95% CI, 1.25–2.66) in a heterogeneous set of studies (I2 = 81.2%, p = 0.000).ConclusionOur findings indicate that elevated TNF-α levels in the blood are associated with an increased risk of CP. The association of TNF-α with CP requires further investigation.