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

被引:42
作者
Van den Tweel, ERW
Kavelaars, A
Lombardi, MS
Nijboer, CHA
Groenendaal, F
Van Bel, F
Heijnen, CJ
机构
[1] Univ Utrecht, Ctr Med, Lab Psychoneuroimmunol & Perinatol, NL-3508 AB Utrecht, Netherlands
[2] Univ Utrecht, Ctr Med, Dept Neonatol, NL-3584 EA Utrecht, Netherlands
[3] Univ Utrecht, Ctr Med, Lab Psychoneuroimmunol & Perinatol, NL-3584 EA Utrecht, Netherlands
关键词
D O I
10.1203/01.pdr.0000200799.64038.19
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
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% O-2, 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)-1 alpha protein increased with a peak at 3 h after HI. mRNA expression for IL-beta and tumor necrosis factor-alpha and -beta 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-alpha 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-1 alpha, 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.
引用
收藏
页码:434 / 439
页数:6
相关论文
共 32 条
[1]   MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia [J].
Alessandrini, A ;
Namura, S ;
Moskowitz, MA ;
Bonventre, JV .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (22) :12866-12869
[2]   Novel signal transduction pathway utilized by extracellular HSP70 -: Role of Toll-like receptor (TLR) 2 AND TLR4 [J].
Asea, A ;
Rehli, M ;
Kabingu, E ;
Boch, JA ;
Baré, O ;
Auron, PE ;
Stevenson, MA ;
Calderwood, SK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (17) :15028-15034
[3]  
Bergeron M, 2000, ANN NEUROL, V48, P285, DOI 10.1002/1531-8249(200009)48:3<285::AID-ANA2>3.0.CO
[4]  
2-8
[5]   Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats [J].
Bona, E ;
Andersson, AL ;
Blomgren, K ;
Gilland, E ;
Puka-Sundvall, M ;
Gustafson, K ;
Hagberg, H .
PEDIATRIC RESEARCH, 1999, 45 (04) :500-509
[6]   Origin and timing of brain lesions in term infants with neonatal encephalopathy [J].
Cowan, F ;
Rutherford, M ;
Groenendaal, F ;
Eken, P ;
Mercuri, E ;
Bydder, GM ;
Meiners, LC ;
Dubowitz, LMS ;
de Vries, LS .
LANCET, 2003, 361 (9359) :736-742
[7]   COMPARATIVE ASPECTS OF THE BRAIN GROWTH SPURT [J].
DOBBING, J ;
SANDS, J .
EARLY HUMAN DEVELOPMENT, 1979, 3 (01) :79-83
[8]   Reperfusion injury as the mechanism of brain damage after perinatal asphyxia [J].
Fellman, V ;
Raivio, KO .
PEDIATRIC RESEARCH, 1997, 41 (05) :599-606
[9]   Vanadate-induced expression of hypoxia-inducible factor 1α and vascular endothelial growth factor through phosphatidylinositol 3-kinase/Akt pathway and reactive oxygen species [J].
Gao, N ;
Ding, M ;
Zheng, JZ ;
Zhang, Z ;
Leonard, SS ;
Liu, KJ ;
Shi, XL ;
Jiang, BH .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (35) :31963-31971
[10]   Heat shock proteins: Endogenous modulators of apoptotic cell death [J].
Garrido, C ;
Gurbuxani, S ;
Ravagnan, L ;
Kroemer, G .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2001, 286 (03) :433-442