RESUMO
Exogenous bone marrow-derived cells (BMDCs) are promising therapeutic agents for the treatment of tissue ischemia and traumatic injury. However, until we identify the molecular mechanisms that underlie their actions, there can be no rational basis for the design of therapeutic strategies using BMDCs. The pro-healing effects of BMDCs are apparent very shortly after treatment, which suggests that they may exert their effects by the modulation of acute inflammation. We investigated this hypothesis by taking advantage of the fact that BMDCs from healthy, young, but not obese, diabetic mice stimulate vascular growth. By comparing both in vitro secretion and in vivo local induction of acute phase inflammatory cytokines by these cells, we identified monocyte chemoattractant factor 1 and tumor necrosis factor α as potential mediators of BMDC-induced tissue repair. In vivo analysis of BMDC-treated ischemic limbs and cutaneous wounds revealed that the production of monocyte chemoattractant factor 1 by exogenous and endogenous BMDCs is essential for BMDC-mediated vascular growth and tissue healing, while the inability of BMDCs to produce tumor necrosis factor α appears to play a lesser but still meaningful role. Thus, measurements of the secretion of cytokines by BMDCs may allow us to identify a priori individuals who would or would not be good candidates for BMDC-based therapies.
Assuntos
Medula Óssea/metabolismo , Medula Óssea/patologia , Quimiocina CCL2/metabolismo , Inflamação/prevenção & controle , Isquemia/prevenção & controle , Receptores para Leptina/metabolismo , Cicatrização , Animais , Western Blotting , Células Cultivadas , Citocinas/metabolismo , Extremidades , Técnicas Imunoenzimáticas , Inflamação/etiologia , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Isquemia/etiologia , Isquemia/metabolismo , Camundongos , Camundongos Knockout , Pele/lesões , Fator de Necrose Tumoral alfa/fisiologiaRESUMO
Pediatric head injuries are common and may present with varying degrees of altered mental status in children. The approach to evaluation, diagnosis, treatment, and prevention of further injury is important in achieving good health outcomes after a head injury. In this article, we review the pathophysiology, classifications, signs and symptoms, and management of traumatic brain injury. We also discuss the importance of preventing a secondary injury during recovery by educating families about head injury sequelae and return-to-play guidelines. [Pediatr Ann. 2019;48(5):e192-e196.].