Abstract |
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.
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Authors | Ylva Carlsson, Anna-Lena Leverin, Maj Hedtjärn, Xiaoyang Wang, Carina Mallard, Henrik Hagberg |
Journal | Developmental neuroscience
(Dev Neurosci)
Vol. 31
Issue 5
Pg. 420-6
( 2009)
ISSN: 1421-9859 [Electronic] Switzerland |
PMID | 19672071
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | (c) 2009 S. Karger AG, Basel. |
Chemical References |
- Carbazoles
- 3,9-bis((ethylthio)methyl)-K-252a
- Caspase 3
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Topics |
- Animals
- Animals, Newborn
- Apoptosis
(drug effects)
- Blotting, Western
- Brain
(drug effects, metabolism, pathology)
- Carbazoles
(pharmacology)
- Caspase 3
(metabolism)
- Cell Count
- Enzyme-Linked Immunosorbent Assay
- Hypoxia-Ischemia, Brain
(drug therapy, metabolism)
- Image Processing, Computer-Assisted
- Immunohistochemistry
- In Situ Nick-End Labeling
- Inflammation
(metabolism)
- Microglia
(drug effects, metabolism)
- Neurons
(drug effects, metabolism)
- Organ Size
(drug effects)
- Rats
- Rats, Wistar
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction
(drug effects)
- Statistics, Nonparametric
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