Intrauterine infection/inflammation and perinatal brain damage: role of glial cells and Toll-like receptor signaling.
The mechanisms or pathophysiology that leads to preterm brain damage including white matter damage during development are complex and not fully understood. Intrauterine infection/inflammation can significantly affect perinatal brain development and result in significant alterations in brain structure and function. Glial cells and Toll-like receptors (TLRs) are vital players in central nervous system immune response; dysregulation of this response plays an important role in brain damage. Intrauterine infection/inflammation has immunomodulatory effects and induces specific alterations in the TLRs response in many tissues. Recent findings indicate that intrauterine infection/inflammation could promote inflammatory processes in brain and in glial cells by up-regulating cytokines and inflammatory mediators, and by activating signaling pathways and transcriptional factors (nuclear factor-kappaB) implicated in inflammatory injury. TLRs may be involved in intrauterine infection-mediated inflammatory signaling, and intrauterine infection/inflammation could interfere with the TLR4 recruitment into the lipid rafts, leading to an effect on the TLR signaling transduction. In summary, current results suggest that TLRs are key mediators of intrauterine infection/inflammation induced preterm brain damage.
Yuan
Tian-Ming
TM
Zhejiang Key Laboratory for Diagnosis and Therapy of Neonatal Disease, Department of Neonatology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, PR China.
Sun
Yi
Y
Zhan
Can-Yang
CY
Yu
Hui-Min
HM
D000818:Animals; D001927:Brain Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D008954:Models, Biological; D009457:Neuroglia / Q000502:physiology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology*; D051193:Toll-Like Receptors / Q000378:metabolism*
D051193:Toll-Like Receptors