UNIVERSIDADE FEDERAL DE MINAS GERAIS FACULDADE DE MEDICINA PROGRAMA DE PÓS-GRADUAÇÃO EM MEDICINA MOLECULAR RAFAEL COELHO MAGALHÃES AVALIAÇÃO LONGITUDINAL DA RESPOSTA IMUNO-INFLAMATÓRIA E DO DESENVOLVIMENTO NEUROPSICOMOTOR EM CRIANÇAS COM PARALISIA CEREBRAL Belo Horizonte 2019 UNIVERSIDADE FE

Background: Brain damage in the fetal-neonatal period may have different causes. An exacerbated systemic inflammatory response and/or neuroinflammation have been associated with early brain injury. This persistent inflammatory response may result in abnormal neural mechanism, with consequent limitation in children's functional capacity due to spasticity, reduced coordination and motor control. Cerebral palsy (CP) is one of the main consequences of brain injury in fetal and neonatal period. Rehabilitation interventions may promote functional changes in the brain, which are associated with greater release of neurotrophic factors, besides favoring neuropsychomotor development with learning of new abilities. Objective: To evaluate the effects of rehabilitation program on DNPM, inflammatory markers and neurotrophic factors in children with CP. Methods: A systematic search was conducted in Bireme, Embase, PubMed and Scopus including studies that were published until April 2018. The quality of the eligible studies was determined according to the criteria of Newcastle-Ottawa Scale. We performed a prospective, observational, cohort study to better understand the relationship of cerebral palsy, rehabilitation programs and neuropsychomotor development. Ninety children with a diagnosis of CP were enrolled in this study. Sixty children were submitted to rehabilitation for six months and were compared to 30 children waiting for rehabilitation enrollment. Peripheral biomarkers and neuropsychomotor parameters (Bayley III) were compared between intervention vs. control groups at baseline and six months later. Results: In the systematic review, the studies differed regarding the risk factors related to PC and its classification. Higher levels of cytokines were associated with worse neurological outcomes. In our research, after six months of rehabilitation, children exhibited higher scores on Bayley III, lower levels of IL-12p70, IL-6, IL-1β, CXCL8 / IL-8 and CXCL9 / MIG, and higher levels of BDNF and GDNF. Conclusion: Early intervention programs seem to modulate systemic mediators. It decreases inflammatory molecules levels, increases neurotrophic factors levels, and promotes neuropsychomotor development in children with cerebral palsy. Key-words: Cerebral palsy; inflammation; oxidative stress; cytokines; chemokines; neuropsychomotor development, neurodevelopment outcomes and child.