NF-κB inhibition after neonatal cerebral hypoxia–ischemia improves long-term motor and cognitive outcome in rats

Prophylactic subacute administration of zinc decreases lipoperoxidation and cell death following a transient cerebral hypoxia-ischemia, thus suggesting neuroprotective and preconditioning effects. Chemokines and growth factors are also involved in the neuroprotective effect in hypoxia-ischemia. We explored whether zinc prevents the cerebral cortex-hippocampus injury through regulation of CCL2, CCR2, FGF2, and IGF-1 expression following a 10 min of common carotid artery occlusion (CCAO). Male rats were grouped as follows: (1) Zn96h, rats injected with ZnCl2(one dose every 24 h during four days); (2) Zn96h + CCAO, rats treated with ZnCl2before CCAO; (3) CCAO, rats with CCAO only; (4) Sham group, rats with mock CCAO; and (5) untreated rats. The cerebral cortex-hippocampus was dissected at different times before and after CCAO. CCL2/CCR2, FGF2, and IGF-1 expression was assessed by RT-PCR and ELISA. Learning in Morris Water Maze was achieved by daily training during 5 days. Long-term memory was evaluated on day 7 after learning. Subacute administration of zinc increased expression of CCL2, CCR2, FGF2, and IGF-1 in the early and late phases of postreperfusion and prevented the CCAO-induced memory loss in the rat. These results might be explained by the induction of neural plasticity because of the expression of CCL2 and growth factors.

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Delayed Postischemic Hypothermia Improves Long-Term Behavioral Outcome after Cerebral Hypoxia-Ischemia in Neonatal Rats

Pediatric Research ◽

10.1203/00006450-200203000-00015 ◽

2002 ◽

Vol 51 (3) ◽

pp. 354-360 ◽

Cited By ~ 103

Author(s):

Bendicht Peter Wagner ◽

Johann Nedelcu ◽

Ernst Martin

Keyword(s):

Cerebral Hypoxia ◽

Neonatal Rats ◽

Behavioral Outcome ◽

Hypoxia Ischemia

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Oxygen treatment after perinatal hypoxia-ischemia reduces neuronal damage at short survival times, but worsens injury with long-term survival

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/sj.jcbfm.9591524.0444 ◽

2005 ◽

Vol 25 (1_suppl) ◽

pp. S444-S444 ◽

Cited By ~ 1

Author(s):

Kristin M Noppens ◽

J Regino Perez-Polo ◽

David K Rassin ◽

Karin N Westlund ◽

Roderic Fabian ◽

...

Keyword(s):

Neuronal Damage ◽

Perinatal Hypoxia ◽

Survival Times ◽

Term Survival ◽

Long Term Survival ◽

Short Survival ◽

Oxygen Treatment ◽

Hypoxia Ischemia

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Long-term Motor and Cognitive Outcome of Acute Encephalitis

PEDIATRICS ◽

10.1542/peds.2013-3010d ◽

2014 ◽

Vol 133 (3) ◽

pp. X22-X22

Keyword(s):

Cognitive Outcome ◽

Acute Encephalitis

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Human milk feeding and cognitive outcome in preterm infants: the role of infection and NEC reduction

Pediatric Research ◽

10.1038/s41390-021-01367-z ◽

2021 ◽

Author(s):

Winok Lapidaire ◽

Alan Lucas ◽

Jonathan D. Clayden ◽

Chris Clark ◽

Mary S. Fewtrell

Keyword(s):

Breast Milk ◽

Human Milk ◽

Preterm Infants ◽

Neonatal Infection ◽

Necrotising Enterocolitis ◽

Cognitive Outcome ◽

Standard Diet ◽

Risk Of Infection ◽

Verbal Iq

Abstract Background Breast milk has been associated with lower risk of infection and necrotising enterocolitis (NEC) and improved long-term cognitive outcomes in preterm infants but, if unsupplemented, does not meet the nutritional requirements of preterm infants. Methods Preterm infants were randomised to receive a high nutrient intervention diet: preterm formula (PTF) or the standard diet: term formula (TF) or banked donor breast milk (BBM), either as their sole diet or as supplement to maternal breast milk (MBM). IQ tests were performed at ages 7, 15, 20, and 30 years. Results An increase in MBM and BBM intake was associated with a lower chance of neonatal infection/NEC. Neonatal infection/NEC was associated with lower Full Scale IQ (FSIQ) and Performance IQ (PIQ) score at ages 7 and 30 years. The relationship between higher intake of MBM and PIQ at age 7 years was partly mediated by neonatal infection/NEC. The intervention diet was associated with higher Verbal IQ (VIQ) scores compared to the standard diet. There was no evidence that these effects changed from childhood through to adulthood. Conclusions Neonatal diet is an important modifiable factor that can affect long-term cognitive outcome through a ‘human milk’ factor, protecting against infection/NEC, and a ‘nutrient content’ factor. Impact This is the first study to demonstrate the effects of neonatal infection/necrotising enterocolitis (NEC) on IQ in the same cohort in childhood and adulthood. Diet can be a key factor in long-term cognitive outcome in people born preterm by preventing neonatal infection/NEC and providing adequate nutrients. Human milk, whether MBM or BBM, is associated with a reduced risk of infection/NEC. A higher nutrient diet is associated with better cognitive outcome in childhood. Performance IQ is particularly vulnerable to the effects of infection/NEC and verbal IQ to the quantity of (macro)nutrients in the diet.

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