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Hypoxia‐induced ischemic tolerance in neonatal rat brain involves enhanced ERK1/2 signaling
Author(s) -
Jones Nicole M.,
Bergeron Marcelle
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2004.02324.x
Subject(s) - neuroprotection , hypoxia (environmental) , mapk/erk pathway , protein kinase b , pi3k/akt/mtor pathway , signal transduction , kinase , biology , phosphorylation , brain damage , endocrinology , microbiology and biotechnology , pharmacology , chemistry , neuroscience , organic chemistry , oxygen
Hypoxic preconditioning (HP) 24 h before hypoxic‐ischemic (HI) injury confers significant neuroprotection in neonatal rat brain. Recent studies have shown that the mitogen‐activated protein kinase (MAPK) and phosphatidylinositol‐3‐kinase (PI3K) intracellular signaling pathways play a role in the induction of tolerance to ischemic injury in heart and brain. To study the role of MAPK (ERK1/2, JNK, p38MAPK) and PI3K/Akt/GSK3β signaling pathways in hypoxia‐induced ischemic tolerance, we examined the brains of newborn rats at different time points after exposure to sublethal hypoxia (8% O 2 for 3 h). Immunoblot analysis showed that HP had no effect on the levels of phosphorylated Akt, GSK3β, JNK and p38MAPK. In contrast, significantly increased levels of phosphorylated ERK1/2 were observed 0.5 h after HP. Double immunofluorescence staining showed that hypoxia‐induced ERK1/2 phosphorylation was found mainly in microvessels throughout the brain and in astrocytes in white matter tracts. Inhibition of hypoxia‐induced ERK1/2 pathway with intracerebral administration of U0126 significantly attenuated the neuroprotection afforded by HP against HI injury. These findings suggest that activation of ERK1/2 signaling may contribute to hypoxia‐induced tolerance in neonatal rat brain in part by preserving vascular and white matter integrity after HI.