The protective effects of urocortin1 against intracerebral hemorrhage by activating JNK1/2 and p38 phosphorylation and further increasing VEGF via corticotropin-releasing factor receptor 2.

Abstract

Urocortin (UCN) has exhibited antiinflammatory and neuroprotective effects on intracerebral hemorrhage (ICH). However, the underlying mechanisms are still not clear. Therefore, this study was aimed to investigate effects of UCN1 on ICH in vitro and in vivo and further explore the possible mechanism. ICH was induced by an infusion of autologous blood into the unilateral striatum of anesthetized male Sprague-Dawley rats. The rats were randomly divided into three groups (8 rats per group): sham ICH control group, ICH saline group and ICH UCN1 group. UCN1 was infused into the lateral ventricle after 1h post-ICH. Neurological deficits were evaluated by modified neurological severity score (mNSS). Brain edema was assessed using the dry/wet method. The neurological cell metabolic activity of N2a and SH-SY5Y was detected by CCK-8. The level of VEGF, JNK and p38 were determined by enzyme-linked immunosorbent assay and western blot. Post-treatment with UCN1 could improve neurological deficits and reduce brain edema. Moreover, UCN1 could increase the metabolic activity of neuron cells dose-dependently and these effects could be abolished by corticotropin-releasing factor receptor 2 (CRFR2) antagonist anti-Svg-30. Furthermore, the level of VEGF, JNK and p38 were up-regulated by post-treatment with UCN1 via CRFR2. The protective effects of UCN1 against ICH are possibly mediated by activating the phosphorylation of JNK and p38 and further increasing the level of VEGF via CRFR2.

• Authors: Shu Xu, QiuYi Wu, Gang Guo, XinSheng Ding
• Journal: Neuroscience letters (Neurosci Lett) Vol. 589 Pg. 31-6 (Mar 04 2015) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 25576701 (Publication Type: Journal Article)
• Copyright: Copyright © 2015. Published by Elsevier Ireland Ltd.

Chemical References

• Anti-Inflammatory Agents
• CRF receptor type 2
• Neuroprotective Agents
• Receptors, Corticotropin-Releasing Hormone
• Urocortins
• Vascular Endothelial Growth Factor A
• Mitogen-Activated Protein Kinase 9
• Mitogen-Activated Protein Kinase 8
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Brain Edema (pathology)
• Cell Line, Tumor
• Cerebral Hemorrhage (metabolism, physiopathology, prevention & control)
• Enzyme Activation
• Humans
• Male
• Mice
• Mitogen-Activated Protein Kinase 8 (metabolism)
• Mitogen-Activated Protein Kinase 9 (metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Phosphorylation
• Random Allocation
• Rats, Sprague-Dawley
• Receptors, Corticotropin-Releasing Hormone (metabolism)
• Urocortins (pharmacology, therapeutic use)
• Vascular Endothelial Growth Factor A (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)