ISDN2014_0200: Abnormal neuronal migration with ischemic brain injury in extremely preterm infants underlies subsequent cognitive impairment

2015 ◽  
Vol 47 (Part_A) ◽  
pp. 58-59 ◽  
Author(s):  
K. Deguchi ◽  
K. Kubo ◽  
D.L. Armstrong ◽  
K. Nakajima ◽  
K. Inoue
2011 ◽  
Vol 100 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Su-Jin Noh ◽  
Jong Min Lee ◽  
Ki Sung Lee ◽  
Hyun Su Hong ◽  
Chul Kyu Lee ◽  
...  

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Li-Juan Min ◽  
Masaki Mogi ◽  
Kana Tsukuda ◽  
Hui-Yu Bai ◽  
Bao-Shuai Shan ◽  
...  

Objectives: Cerebrovascular damage could breakdown amyloid-β (Aβ) clearance and accelerate Aβ deposition. We examined the interaction between ischemic brain damage and Aβ deposition in cognitive function, focusing on the roles of angiotensin II type 2 (AT 2 ) receptor in vascular smooth muscle cells (VSMC). Methods: Male wild-type mice (WT) or the mice with VSMC-specific AT 2 receptor overexpression (smAT 2 ) were used. Mice were subjected to ICV injection of Aβ1-40. Ischemic brain injury was induced by bilateral common carotid artery occlusion (BCCAO) 24 hours after Aβ1-40 injection. Three weeks after Aβ1-40 injection, cognitive function was evaluated by the Morris water maze test. Brain samples obtained 8 days after Aβ1-40 injection were used to study the related signals. Results: ICV injection of Aβ1-40 in WT showed impaired cognitive function (arriving time to platform at day 5: control, 26.53±4.46 sec; Aβ, 65.35±7.44 sec), whereas BCCAO alone did not decline significantly cognitive function. In contrast, BCCAO following Aβ1-40 injection exhibited more marked cognitive impairment (84.27±8.00 sec) compared to Aβ injection alone with the increase in expressions of NADPH oxidase subunits such as p22phox and p67phox in the hippocampus of mice. Aβ1-40 injection with BCCAO tended to increase the mRNA levels of inflammatory cytokines such as MCP-1 and TNFα. BCCAO significantly enhanced the expression of Aβ clearance factor, RAGE (receptor for advanced glycation end product). Aβ1-40 injection did not increase the neuron pyknosis in the hippocampus, whereas the number of neuron pyknosis was increased significantly with BCCAO (control, 6.33±0.88/field; Aβ with BCCAO, 46.33±4.10/field). On the other hand, smAT 2 did not show cognitive impairment, the changes of the expression for NADPH oxidase subunits and inflammatory cytokines, and neuron pyknosis, which were induced by BCCAO with/without Aβ1-40 injection in WT. Conclusion: Ischemic brain injury could enhance Aβ-induced cognitive impairment with possible involvement of enhanced oxidative stress, neuron degeneration, and breakdown of RAGE-mediated Aβ clearance. AT 2 receptor activation in VSMC could play inhibitory roles in the cognitive decline induced by ischemic brain damage and Aβ deposition.


BMJ ◽  
2019 ◽  
pp. l5678 ◽  
Author(s):  
Kjell Helenius ◽  
Nicholas Longford ◽  
Liisa Lehtonen ◽  
Neena Modi ◽  
Chris Gale

Abstract Objective To determine if postnatal transfer or birth in a non-tertiary hospital is associated with adverse outcomes. Design Observational cohort study with propensity score matching. Setting National health service neonatal care in England; population data held in the National Neonatal Research Database. Participants Extremely preterm infants born at less than 28 gestational weeks between 2008 and 2015 (n=17 577) grouped based on birth hospital and transfer within 48 hours of birth: upward transfer (non-tertiary to tertiary hospital, n=2158), non-tertiary care (born in non-tertiary hospital; not transferred, n=2668), and controls (born in tertiary hospital; not transferred, n=10 866). Infants were matched on propensity scores and predefined background variables to form subgroups with near identical distributions of confounders. Infants transferred between tertiary hospitals (horizontal transfer) were separately matched to controls in a 1:5 ratio. Main outcome measures Death, severe brain injury, and survival without severe brain injury. Results 2181 infants, 727 from each group (upward transfer, non-tertiary care, and control) were well matched. Compared with controls, infants in the upward transfer group had no significant difference in the odds of death before discharge (odds ratio 1.22, 95% confidence interval 0.92 to 1.61) but significantly higher odds of severe brain injury (2.32, 1.78 to 3.06; number needed to treat (NNT) 8) and significantly lower odds of survival without severe brain injury (0.60, 0.47 to 0.76; NNT 9). Compared with controls, infants in the non-tertiary care group had significantly higher odds of death (1.34, 1.02 to 1.77; NNT 20) but no significant difference in the odds of severe brain injury (0.95, 0.70 to 1.30) or survival without severe brain injury (0.82, 0.64 to 1.05). Compared with infants in the upward transfer group, infants in the non-tertiary care group had no significant difference in death before discharge (1.10, 0.84 to 1.44) but significantly lower odds of severe brain injury (0.41, 0.31 to 0.53; NNT 8) and significantly higher odds of survival without severe brain injury (1.37, 1.09 to 1.73; NNT 14). No significant differences were found in outcomes between the horizontal transfer group (n=305) and controls (n=1525). Conclusions In extremely preterm infants, birth in a non-tertiary hospital and transfer within 48 hours are associated with poor outcomes when compared with birth in a tertiary setting. We recommend perinatal services promote pathways that facilitate delivery of extremely preterm infants in tertiary hospitals in preference to postnatal transfer.


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