U0126 protects hippocampal CA1 neurons against forebrain ischemia-induced apoptosis via the ERK1/2 signaling pathway and NMDA receptors.

Abstract

OBJECTIVE:

Cerebral ischemia can trigger the ERK1/2 signaling cascade that enables the brain to adapt to ischemic injury. However, the mechanism of ERK1/2 in ischemic brain injury remains unclear. The aim of this study was to examine the roles of the ERK1/2 signaling pathway and NMDA receptors in the apoptosis of CA1 pyramidal neurons after ischemia/reperfusion (I/R).

METHODS:

Male Wistar rats were subjected to a sham or transient forebrain ischemia procedure. Animals received the intracerebroventricular injection of U0126 (5 μl, 0.2 μg/μl) or vehicle 30 min before ischemia. Homogenates of the hippocampal CA1 field were obtained from sham-operated and ischemic rats 6, 12 or 48 h after ischemia/reperfusion (n = 6 per group) and then subjected to Western blotting analysis and TUNEL staining. Caspase-3 activity was assayed with a colorimetric assay kit.

RESULTS:

We found that the phosphorylation level of ERK1/2 is increased in the CA1 region following transient I/R. Blocking the ERK1/2 signaling pathway by administration U0126 attenuated apoptotic neuronal cell death via inhibition of NMDA receptors.

CONCLUSION:

These findings suggest a novel mechanism by which the ERK1/2 signaling pathway affects the post-I/R apoptosis of CA1 pyramidal neurons, which will provide a therapeutic target for the treatment of stroke.

• Authors: Jianguo Li, Deping Yan, Xiaoyan Liu, Ye Wang, Xin Zhao, Yu Zhang, Ce Zhang
• Journal: Neurological research (Neurol Res) Vol. 40 Issue 4 Pg. 318-323 (Apr 2018) ISSN: 1743-1328 [Electronic] England
• PMID: 29473447 (Publication Type: Journal Article)

Chemical References

• Butadienes
• Neuroprotective Agents
• Nitriles
• Receptors, N-Methyl-D-Aspartate
• U 0126

Topics

• Animals
• Apoptosis
• Brain Ischemia (complications, metabolism)
• Butadienes (administration & dosage)
• CA1 Region, Hippocampal (drug effects, metabolism)
• MAP Kinase Signaling System (drug effects)
• Male
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (administration & dosage)
• Nitriles (administration & dosage)
• Phosphorylation
• Prosencephalon (injuries)
• Rats, Wistar
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, metabolism)