Developmental neuroscience · 2009
Role of mixed lineage kinase inhibition in neonatal hypoxia-ischemia.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Carlsson Ylva, Leverin Anna-Lena, Hedtjärn Maj, Wang Xiaoyang, Mallard Carina, Hagberg Henrik
Аннотация
Hypoxic-ischemic brain injury is often delayed and involves both apoptotic and immunoregulatory mechanisms. In this study, we used a neonatal model of hypoxia-ischemia to examine the effect of the mixed lineage kinase (MLK) inhibitor CEP-1347 on brain damage, apoptosis and inflammation. The tissue volume loss was reduced by 28% (p = 0.019) in CEP-1347-treated versus vehicle-treated rats and CEP-1347 significantly attenuated microgliosis at 7 days (p = 0.038). CEP-1347 decreased TUNEL-positive staining as well as cleaved caspase 3 immunoreactivity. CEP-1347 did not affect the expression of pro-inflammatory cytokines IL-1 beta, IL-6 and MCP-1, nor did it affect the expression of OX-42 (CR3) and OX-18 (MHC I) 24 h after the insult. In conclusion, the MLK inhibitor CEP-1347 has protective effects in a neonatal rat model of hypoxia-ischemia, which is mainly related to reduced apoptosis.
Предметные рубрики MeSH
AnimalsAnimals, NewbornApoptosisBlotting, WesternBrainCarbazolesCaspase 3Cell CountEnzyme-Linked Immunosorbent AssayHypoxia-Ischemia, BrainImage Processing, Computer-AssistedImmunohistochemistryIn Situ Nick-End LabelingInflammationMicrogliaNeuronsOrgan SizeRatsRats, WistarReverse Transcriptase Polymerase Chain ReactionSignal TransductionStatistics, Nonparametric