Dexamethasone reduces brain cell apoptosis and inhibits inflammatory response in rats with intracerebral hemorrhage.

Abstract

Spontaneous intracerebral hemorrhage (ICH) is associated with high rates of mortality and morbidity. Thus, the identification of novel therapeutic agents for preventing strokes and attenuating poststroke brain damage is crucial. Dexamethasone (DEX) is used clinically to reduce edema formation in patients with spinal cord injury and brain tumors. In this study, we sought to elucidate the effects of DEX treatment on apoptosis and inflammation following ICH in rats. A high dose of DEX (15 mg/kg) was administered immediately following ICH induction and again 3 days later. The inflammatory and apoptotic responses in the rat brains were evaluated by using hematoxylin-eosin, terminal deoxynucleotidyl transferase dUTP nick end labeling, Nissl, and neurofilament-H staining. Levels of phosphorylated neurofilaments and apoptosis-related proteins such as B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), caspase-3, and P53 were analyzed by Western blotting. This study shows that rats without ICH that received DEX treatment had a fourfold higher expression of Bcl-2 than sham-operated rats. ICH causes an increase in Bax, cleaved caspase-3, and P53 proteins from 4 hr to 7 days following ICH induction. In comparison with the ICH rats, the ICH/DEX rats showed significantly decreased apoptotic cell death and increased neuron survival and maintained neurofilament integrity in the perihematomal region. DEX increased the Bcl-2/Bax ratio and lowered the expression of cleaved caspase-3 at 12 hr and 5 days. The ICH rats were accompanied by activation of the inflammatory response, and DEX treatment modulated the expression of a variety of cell types and then decreased ICH-induced apoptosis.

• Authors: I-Neng Lee, Wan-Chun Cheng, Chiu-Yen Chung, Ming-Hsueh Lee, Martin Hsiu-Chu Lin, Chia-Hui Kuo, Hsu-Huei Weng, Jen-Tsung Yang
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 93 Issue 1 Pg. 178-88 (Jan 2015) ISSN: 1097-4547 [Electronic] United States
• PMID: 25042403 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• Anti-Inflammatory Agents
• CD3 Complex
• Neurofilament Proteins
• Proto-Oncogene Proteins c-bcl-2
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• neurofilament protein H
• Dexamethasone
• 2',3'-Cyclic-Nucleotide Phosphodiesterases

Topics

• 2',3'-Cyclic-Nucleotide Phosphodiesterases (metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Brain (drug effects, pathology)
• CD3 Complex (metabolism)
• Cerebral Hemorrhage (complications)
• DNA Fragmentation (drug effects)
• Dexamethasone (pharmacology, therapeutic use)
• Disease Models, Animal
• Encephalitis (drug therapy, etiology, pathology)
• Male
• Neurofilament Proteins (metabolism)
• Neurons (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Rats
• Rats, Sprague-Dawley
• Tumor Suppressor Protein p53 (metabolism)
• bcl-2-Associated X Protein (metabolism)