LAUSR

neuroinflammatory processes seem to also play a crucial role in the development of MMC-associated sequelae such as secondary TCS. However, the question as to when exactly these mediators are induced in the long-term course after initial MMC repair surgeries remains unanswered. The excessive cytokine immunoreactivity may reflect a chronic on- going or acute inflammatory reaction, which, together with other mechanical and hypoxia-related factors, might underlie the pathogenesis of symptomatic re-tethering. Further functional studies are needed to evaluate the significance of these findings. The presented studies demonstrated a potential role of pro-inflammatory cytokines such as IL-1β and TNF-α in the late fetal, perinatal, and further post-natal time- points in MMC neural placodes of rat and human origin. Along with other factors, these cytokines are well-known molecular mediators of secondary lesion cascades, which are induced after traumatic SCI. Under pathological conditions, these mediators exceed their normal expression level and become involved in pro-inflammatory and pro-apoptotic cascades, which have the potential to further damage primarily intact tissue (summarized under the term “second lesion” in the neurotrauma literature). Because mechanical injury to the neural placode is considered one crucial factor of the “second hit”, one can postulate that similar processes are induced in the neural placode. Strong gliosis and the appearance of inflammatory cells in the neuroepithelia of fetal rat and newborn human MMC specimens indicated that such damaging processes take place in open spinal dysraphism. It may be that limited intra-uterine space in addition to changes of amniotic fluid consistency increases the probability of damaging insults to the exposed neural epithelium. This may explain the elevated cytokine expression level at later fetal and prenatal time points in our studies. With their proinflammatory and pro-apoptotic properties, induction of TNF-α and IL-1β may promote further neuronal damage and thus decline neural function.