Locomotion is impacted differently according to the perinatal brain injury model: Meta-analysis of preclinical studies with implications for cerebral palsy.

Background: Different approaches to reproduce cerebral palsy (CP) in animals, contribute to the knowledge of the pathophysiological mechanism of this disease and provide a basis for the development of intervention strategies. Locomotion and coordination are the main cause of disability in CP, however, few studies highlight the quantitative differences of CP models, on locomotion parameters, considering the methodologies to cause brain lesions in the perinatal period.

Methods: Studies with cerebral palsy animal models that assess locomotion parameters were systematically retrieved from Medline/PubMed, SCOPUS, LILACS, and Web of Science. Methodological evaluation of included studies and quantitative assessment of locomotion parameters were performed after eligibility screening.

Results: CP models were induced by hypoxia-ischemia (HI), Prenatal ischemia (PI), lipopolysaccharide inflammation (LPS), intraventricular haemorrhage (IVH), anoxia (A), sensorimotor restriction (SR), and a combination of different models. Overall, 63 studies included in qualitative synthesis showed a moderate quality of evidence. 16 studies were included in the quantitative meta-analysis. Significant reduction was observed in models that combined LPS with HI related to distance traveled (SMD -7.24 95 % CI [-8.98, -5.51], Z = 1.18, p < 0.00001) and LPS with HI or anoxia with sensory-motor restriction (SMD -6.01, 95 % CI [-7.67, -4.35], Z = 7.11), or IVH (SMD -4.91, 95 % CI [-5.84, -3.98], Z = 10.31, p < 0.00001) related to motor coordination.

Conclusion: The combination of different approaches to reproduce CP in animals causes greater deficits in locomotion and motor coordination from the early stages of life to adulthood. These findings contribute to methodological refinement, reduction, and replacement in animal experimentation, favoring translational purposes.