The signal transduction mediated by erythropoietin and proinflammatory cytokines in the JAK/STAT pathway in the children with cerebral palsy

It is well established that erythropoietin (EPO) is a pleiotropic cytokine, which has a brain-derived neuroprotective effect in the central nervous system (CNS). Immune abnormality has a close relationship with cerebral palsy (CP), and may be even involved in the development of CP. There is evidence that the amount of EPO in CP children is lower than in normal children, but the levels of proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are higher in the CP children. The signal transduction mediated by EPO that has a neuroprotective effect and mediated by proinflammatory cytokines that lead to brain damage shares the common JAK/STAT pathway. Under acute stress, the JAK/STAT pathway is occupied by massive proinflammatory cytokines, and the negative feedback inhibition factors like suppressor of cytokine signaling (SOCS) proteins are simultaneously activated, which exist in reciprocal inhibition to EPO in the JAK/STAT pathway. As a result, the signal transduction mediated by EPO is prevented or reduced, and the neuroprotective effect of EPO is eventually weakened. In this review, a novel approach to CP treatment through neurodevelopmental treatment (NDT) is put forward by analysis of the interrelationship of signal transduction mediated by EPO and proinflammatory cytokines in the JAK/STAT pathway and their roles in the development of CP, and some reasonable ideas for CP treatment are provided.