Dexmedetomidine Up-regulates Brain-derived Neurotrophic Factor via Nrf2 in a Mouse Middle Cerebral Artery Occlusion Model.

Background/aim: The middle cerebral artery occlusion (MCAO) model is widely used to study stroke pathobiology. Dexmedetomidine (DEX) has demonstrated neuroprotective effects in ischemic brain models. Previous studies have shown that nuclear factor erythroid 2-related factor 2 (Nrf2) expression changes in the parietal cortex, which is supplied by the middle cerebral artery, after ischemic injury. While Nrf2 is known to regulate brain-derived neurotropic factor (BDNF) expression, its role in MCAO conditions has not been fully explored. This study aimed to investigate the effects of DEX on Nrf2 and BDNF expression in the parietal cortex following MCAO.

Materials and methods: Mice were subjected to MCAO by inserting a silicone-coated suture into the common carotid artery. After 30 min, the suture was withdrawn to induce ischemia/reperfusion (IR) injury. Cortical brain tissues were harvested three days post-injury. Western blot analysis was performed to measure BDNF protein expression. The expression levels of the messenger ribonucleic acid (mRNA) Nrf2, pro-apoptotic protein (Bax), and anti-apoptotic protein (Bcl-2) were analyzed using quantitative real-time polymerase chain reaction.

Results: The mRNA level of Nrf2 was significantly higher in the DEX group than in the MCAO group after three days of MCAO. BDNF protein expression (15 kDa) was also higher in the DEX group than in the MCAO group. Furthermore, Bax mRNA was lower, while Bcl-2 mRNA was higher in the DEX group than in the MCAO group.

Conclusion: DEX treatment up-regulated Nrf2 expression, which was associated with increased BDNF expression three days after MCAO.