TY - JOUR
T1 - Bilateral molecular changes in a neonatal rat model of unilateral hypoxic-ischemic brain damage
AU - Van Den Tweel, Evelyn R.W.
AU - Kavelaars, Annemieke
AU - Lombardi, Maria Stella
AU - Nijboer, Cora H.A.
AU - Groenendaal, Floris
AU - Van Bel, Frank
AU - Heijnen, Cobi J.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2006/3
Y1 - 2006/3
N2 - Perinatal hypoxia ischemia (HI) is a frequent cause of neonatal brain injury. This study aimed at describing molecular changes during the first 48 h after exposure of the neonatal rat brain to HI. Twelve-day-old rats were subjected to unilateral carotid artery occlusion and 90 min of 8% O2, leading to neuronal damage in the ipsilateral hemisphere only. Phosphorylated-Akt levels were decreased from 0.5 to 6 h post-HI, whereas the level of phosphorylated extracellular signal-related kinases (ERK) 1/2 increased during this time frame. Hypoxia-inducible factor (HIF)-1α protein increased with a peak at 3 h after HI. mRNA expression for IL-β and tumor necrosis factor-α and -β started to increase at 6 h with a peak at 24 h post-HI. Expression of heat shock protein 70 was increased from 12 h after HI onwards in the ipsilateral hemisphere only. Surprisingly, HI changed the expression of cytokines, HIF1-α ,and P-Akt to the same extent in both the ipsi- as well as the contralateral hemisphere, although neuronal damage was unilateral. Exposure of animals to hypoxia without carotid artery occlusion induced similar changes in cytokines, HIF-1α, and P-Akt. We conclude that during HI, hypoxia is sufficient to regulate multiple molecular mediators that may contribute, but are not sufficient, to induce long-term neuronal damage.
AB - Perinatal hypoxia ischemia (HI) is a frequent cause of neonatal brain injury. This study aimed at describing molecular changes during the first 48 h after exposure of the neonatal rat brain to HI. Twelve-day-old rats were subjected to unilateral carotid artery occlusion and 90 min of 8% O2, leading to neuronal damage in the ipsilateral hemisphere only. Phosphorylated-Akt levels were decreased from 0.5 to 6 h post-HI, whereas the level of phosphorylated extracellular signal-related kinases (ERK) 1/2 increased during this time frame. Hypoxia-inducible factor (HIF)-1α protein increased with a peak at 3 h after HI. mRNA expression for IL-β and tumor necrosis factor-α and -β started to increase at 6 h with a peak at 24 h post-HI. Expression of heat shock protein 70 was increased from 12 h after HI onwards in the ipsilateral hemisphere only. Surprisingly, HI changed the expression of cytokines, HIF1-α ,and P-Akt to the same extent in both the ipsi- as well as the contralateral hemisphere, although neuronal damage was unilateral. Exposure of animals to hypoxia without carotid artery occlusion induced similar changes in cytokines, HIF-1α, and P-Akt. We conclude that during HI, hypoxia is sufficient to regulate multiple molecular mediators that may contribute, but are not sufficient, to induce long-term neuronal damage.
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U2 - 10.1203/01.pdr.0000200799.64038.19
DO - 10.1203/01.pdr.0000200799.64038.19
M3 - Article
C2 - 16492985
AN - SCOPUS:33646089225
SN - 0031-3998
VL - 59
SP - 434
EP - 439
JO - Pediatric research
JF - Pediatric research
IS - 3
ER -