Perinatal anoxia associated with sensorimotor restriction causes muscle atrophy and microglial activation: Meta-analysis of preclinical studies with implications for cerebral palsy

Abstract

Several experimental cerebral palsy models have been created to investigate cellular and molecular mechanisms involved in this condition and develop new therapeutic strategies. The model that has come closest to a motor phenotype similar to cerebral palsy is the one that combines perinatal anoxia with hindlimb sensorimotor restriction, as it induces visible changes at the peripheral and central levels. This systematic review with meta-analysis presents the impact of the cerebral palsy model that associates perinatal anoxia with hindlimb sensorimotor restriction on the nervous, muscular and skeletal systems. Studies with perinatal anoxia associated with sensorimotor restriction and which evaluated outcomes related to skeletal, muscle, or nervous tissue were recovered from the databases: Embase, PubMed, Scopus, and Web of Science. The methodological and quantitative assessment was performed after eligibility screening (PROSPERO - ID: CRD42023477770). After screening of 4,641 articles, 21 studies with a moderate quality of evidence were chosen to be included in this review and 11 articles were included in the meta-analysis. The results of the meta-analysis reported a significant reduction in the media area of the soleus muscle fibers, increased number of glia cells and glia/neuron index in the somatosensory cortex, increased microglial activation in the hippocampus, and no changes in the corpus callosum thickness or neuron cells. The combination of perinatal anoxia and sensorimotor restriction entails muscle deficits and excessive activation of glial cells in brain areas. These results contribute to a methodological refinement of cerebral palsy models and favor new studies proposed for methodological elucidation in animal experimentation.