Bilateral molecular changes in a neonatal rat model of unilateral hypoxic-ischemic brain damage

Evelyn R.W. Van Den Tweel, Annemieke Kavelaars, Maria Stella Lombardi, Cora H.A. Nijboer, Floris Groenendaal, Frank Van Bel, Cobi J. Heijnen

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)434-439
Number of pages6
JournalPediatric research
Volume59
Issue number3
DOIs
StatePublished - Mar 1 2006

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Brain Hypoxia
Ischemia
Hypoxia-Inducible Factor 1
Carotid Arteries
Cytokines
Brain Hypoxia-Ischemia
Hypoxia
HSP70 Heat-Shock Proteins
Brain Injuries
Phosphotransferases
Tumor Necrosis Factor-alpha
Messenger RNA

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Bilateral molecular changes in a neonatal rat model of unilateral hypoxic-ischemic brain damage. / Van Den Tweel, Evelyn R.W.; Kavelaars, Annemieke; Lombardi, Maria Stella; Nijboer, Cora H.A.; Groenendaal, Floris; Van Bel, Frank; Heijnen, Cobi J.

In: Pediatric research, Vol. 59, No. 3, 01.03.2006, p. 434-439.

Research output: Contribution to journalArticle

Van Den Tweel, Evelyn R.W. ; Kavelaars, Annemieke ; Lombardi, Maria Stella ; Nijboer, Cora H.A. ; Groenendaal, Floris ; Van Bel, Frank ; Heijnen, Cobi J. / Bilateral molecular changes in a neonatal rat model of unilateral hypoxic-ischemic brain damage. In: Pediatric research. 2006 ; Vol. 59, No. 3. pp. 434-439.
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