Indomethacin protects rats from neuronal damage induced by traumatic brain injury and suppresses hippocampal IL-1β release through the inhibition of Nogo-A expression.

Abstract

BACKGROUND:

Nogo-A is a member of the reticulon family of membrane-associated proteins and plays an important role in axonal remodeling. The present study aimed to investigate alterations in Nogo-A expression following traumatic brain injury (TBI)-induced inflammation and neuronal damage.

METHODS:

A weight-drop device was used to deliver a standard traumatic impact to rats. Western blot, RT-PCR and ELISA were used to analyze the expression of Nogo-A and IL-1β. Nogo-A antisense, and an irrelevant control oligonucleotide was intracerebroventricularly infused. We also performed H & E staining and luxol fast blue staining to evaluate the neuronal damage and demyelination resulting from TBI and various treatments.

RESULTS:

Based on RT-PCR and western blot analyses, the expression of Nogo-A was found to be significantly upregulated in the hippocampus beginning eight hours after TBI. In addition, TBI caused an apparent elevation in IL-1β levels and severe neuronal damage and demyelination in the tested animals. All of the TBI-associated molecular and cellular consequences could be effectively reversed by treating the animals with the anti-inflammatory drug indomethacin. More importantly, the TBI-associated stimulation in the levels of both Nogo-A and IL-1β could be effectively inhibited by a specific Nogo-A antisense oligonucleotide.

CONCLUSIONS:

Our findings suggest that the suppression of Nogo-A expression appears to be an early response conferred by indomethacin, which then leads to decreases in the levels of IL-1β and TBI-induced neuron damage.

• Authors: Po-Kuan Chao, Kwok-Tung Lu, Ji-Yi Jhu, Yu-Yuan Peter Wo, Tai-Chun Huang, Long-Sun Ro, Yi-Ling Yang
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 9 Pg. 121 (Jun 07 2012) ISSN: 1742-2094 [Electronic] England
• PMID: 22676811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• Myelin Proteins
• Neuroprotective Agents
• Nogo Proteins
• Rtn4 protein, rat
• Indomethacin

Topics

• Animals
• Brain Injuries (drug therapy, metabolism, pathology)
• Hippocampus (drug effects, metabolism)
• Indomethacin (pharmacology, therapeutic use)
• Interleukin-1beta (antagonists & inhibitors, metabolism)
• Male
• Myelin Proteins (antagonists & inhibitors, biosynthesis, genetics)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Nogo Proteins
• Rats
• Rats, Wistar