1. Indomethacin protects rats from neuronal damage induced by traumatic brain injury and suppresses hippocampal IL-1β release through the inhibition of Nogo-A expression
- Author
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Yu Yuan P. Wo, Tai Chun Huang, Kwok Tung Lu, Yi Ling Yang, Long Sun Ro, Ji Yi Jhu, and Po Kuan Chao
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Traumatic brain injury ,Nogo Proteins ,Indomethacin ,Interleukin-1beta ,Immunology ,Hippocampus ,Inflammation ,Stimulation ,Pharmacology ,Hippocampal formation ,Luxol fast blue stain ,lcsh:RC346-429 ,Cellular and Molecular Neuroscience ,Western blot ,mental disorders ,medicine ,Animals ,Rats, Wistar ,lcsh:Neurology. Diseases of the nervous system ,Neurons ,medicine.diagnostic_test ,business.industry ,Research ,General Neuroscience ,medicine.disease ,Rats ,Neuroprotective Agents ,medicine.anatomical_structure ,Neurology ,nervous system ,IL-1β ,Brain Injuries ,Neuron ,medicine.symptom ,Nogo-A ,business ,psychological phenomena and processes ,Myelin Proteins - 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.
- Published
- 2012