ABSTRACT
Objective:To study the regulatory effects of transforming growth factor beta-activated kinase 1 (TAK1) on microglia pyroptosis in hypoxic-ischemic brain damage (HIBD).Methods:Primary microglia cells were isolated from fetal mice and randomly assigned into 4 groups: the control group, 5z-7-oxozeaneol (5z-7) group, oxygen-glucose deprivation (OGD) group and OGD+5z-7 group. OGD models of microglia cells were established for the OGD groups and 5z-7 groups received a small molecule TAK1 inhibitor 5z-7. Expression of phosphorylated TAK1(P-TAK1), pyroptosis related proteins including NOD-like receptor pyrin domain containing 3 (NLRP-3), apoptosis-associated speck-like protein containing a CARD (ASC) oligomers, N terminal of Gasdermin D (GSDMD-N) and interleukin 1β (IL-1β) were examined using Western blot at 0 h, 6 h and 24 h after intervention. Lactate dehydrogenase (LDH) test and transmission electron microscope were used for pyroptosis evaluation.Results:(1) Compared with the control group, expressions of all proteins including P-TAK1, NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH level showed no significant differences in the OGD group at 0 h ( P>0.05). P-TAK1 levels in OGD group at 6 h and 24 h were lower than the control group and the levels of NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH were significantly higher ( P<0.05). Microglia pyroptosis (characterized by disruption of cell membrane, extravasation of cytoplasm and chromatin margin aggregation) was observed under electron microscope. (2) 5z-7 group and OGD+5z-7 group had lower P-TAK1 levels and higher NLRP-3, ASC oligomers, GSDMD-N, IL-1β and LDH levels than the control group and OGD group at 6 h and 24 h. Conclusions:The down-regulation of TAK1 phosphorylation level may promote microglia pyroptosis in HIBD. This regulatory effects is related to the up-regulation of NLRP-3 expression and the oligomerization of ASC.
ABSTRACT
Objective To explore the correlation between the fluctuation of blood glucose levels and brain damage in neonates with hypoglycemia. Methods The clinical data of 58 cases of neonatal hypoglycemia diagnosed from September 2013 to August 2016 were analyzed retrospectively. According to the results of neonatal cranial MRI and/or amplitude integrated electroencephalogram (aEEG), the neonates were divided into brain injury group and non-brain injury group. The fluctuation index of blood glucose was compared between two groups, and the correlation between the fluctuation of blood glucose level and brain injury was analyzed. Results In these 58 cases, 13 cases were in brain injury group (8 males and 5 females) and 45 cases were in non-brain injury group (27 males and 18 females). The lowest blood glucose (LBG) value in brain injury group was lower than that in non-brain injury group, while the duration of hypoglycemia, maximum blood glucose fluctuations (LAGE), standard deviation of blood glucose (SDBG), and average blood glucose fluctuations (MAGE) were higher than those in non-brain injury group, and they were all significantly different (P all<0.001). Conclusions Whether the hypoglycemia in newborn could lead to the brain injury or not depends not only on the minimum hypoglycaemia level and duration of hypoglycemia, but also on the indicators of glucose variation, such as LAGE, SDBG and MAGE.