Related Experiment Video
Updated: Jun 14, 2026
Herbal Munziq Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting Inflammation
Published on: January 10, 2025
Age and meloxicam attenuate the ischemia/reperfusion-induced down-regulation in the NMDA receptor genes
Sheyla Montori1, Severiano Dos-Anjos, Beatriz Martínez-Villayandre
1Area de Biología Celular, Instituto de Biomedicina, Universidad de León, 24071 León, Spain.
Abstract:
This study describes the effect of global brain ischemia followed by 48 h reperfusion, when delayed neuronal death can be already observed. We quantified the mRNA levels of the N-methyl-D-aspartate receptor (NMDAR) subunits and those of the astroglia (glial fibrilar acidic protein, GFAP) and microglia (CD11b) markers using real time PCR on the cerebral cortex and hippocampus of 3- and 18-month-old Sprague-Dawley rats. Data show an ischemia/reperfusion-induced decrease in the mRNA levels of the NMDAR NR1, NR2A and NR2B subunits genes, which contrasts with the increase in the CD11b and GFAP mRNA levels. These effects are attenuated in all the genes studied in 18-month-old animals, suggesting that this mechanism of response is less efficient in aged animals. Western blot assays of NR1, NR2A and NR2B show parallels with the real time PCR data, indicating that the down-regulation of these genes is controlled at the transcriptional level. We suggest that a decrease in the efficiency in the control of the NMDAR transcription could account for the higher vulnerability in aged animals, but it cannot explain by itself differences in the vulnerability to ischemia in different areas of the brain. In the assays of ischemia/reperfusion followed by a treatment with the anti-inflammatory agent meloxicam, we observed that ischemic insult was unable to elicit changes in the NMDAR transcription, thus suggesting that inflammation plays a crucial role in the transcriptional control of these genes.
Insights
Global brain ischemia impacts N-methyl-D-aspartate receptor (NMDAR) gene expression, with effects attenuated in aged rats. Inflammation plays a key role in regulating NMDAR transcription following ischemic events.
Area of Science:
- Neuroscience
- Molecular Biology
- Aging Research
Background:
- Global brain ischemia and reperfusion can lead to delayed neuronal death.
- N-methyl-D-aspartate receptor (NMDAR) subunits are crucial for neuronal function and plasticity.
- Aging can alter brain vulnerability to ischemic injury.
Purpose of the Study:
- To investigate the impact of global brain ischemia/reperfusion on NMDAR subunit mRNA levels in young and aged rats.
- To examine the role of glial markers (GFAP, CD11b) in response to ischemia/reperfusion.
- To explore the influence of inflammation on NMDAR gene transcription during ischemic events.
Main Methods:
- Real-time PCR was used to quantify mRNA levels of NMDAR subunits (NR1, NR2A, NR2B), GFAP, and CD11b in rat cerebral cortex and hippocampus.
- Western blot assays were performed to validate gene expression changes at the protein level.
- The effect of the anti-inflammatory drug meloxicam on NMDAR transcription post-ischemia was assessed.
Main Results:
- Ischemia/reperfusion decreased NMDAR subunit mRNA levels (NR1, NR2A, NR2B) but increased glial markers (CD11b, GFAP).
- These changes were less pronounced in 18-month-old rats compared to 3-month-old rats, indicating attenuated responses in aged animals.
- Western blot data confirmed transcriptional control of NMDAR down-regulation. Meloxicam treatment prevented ischemia-induced changes in NMDAR transcription.
Conclusions:
- Reduced NMDAR transcription control efficiency may contribute to increased vulnerability in aged animals.
- Inflammation significantly influences the transcriptional regulation of NMDAR genes during ischemic insult.
- While NMDAR transcription changes are observed, they do not fully explain regional differences in brain vulnerability to ischemia.
