The Mechanism of the Neuroprotective Effect of Kynurenic Acid in the Experimental Model of Neonatal Hypoxia-Ischemia: The Link to Oxidative Stress.
Ewelina Bratek-GerejApolonia ZiembowiczJakub GodlewskiElzbieta SalinskaPublished in: Antioxidants (Basel, Switzerland) (2021)
The over-activation of NMDA receptors and oxidative stress are important components of neonatal hypoxia-ischemia (HI). Kynurenic acid (KYNA) acts as an NMDA receptor antagonist and is known as a reactive oxygen species (ROS) scavenger, which makes it a potential therapeutic compound. This study aimed to establish the neuroprotective and antioxidant potential of KYNA in an experimental model of HI. HI on seven-day-old rats was used as an experimental model. The animals were injected i.p. with different doses of KYNA 1 h or 6 h after HI. The neuroprotective effect of KYNA was determined by the measurement of brain damage and elements of oxidative stress (ROS and glutathione (GSH) level, SOD, GPx, and catalase activity). KYNA applied 1 h after HI significantly reduced weight loss of the ischemic hemisphere, and prevented neuronal loss in the hippocampus and cortex. KYNA significantly reduced HI-increased ROS, GSH level, and antioxidant enzyme activity. Only the highest used concentration of KYNA showed neuroprotection when applied 6 h after HI. The presented results indicate induction of neuroprotection at the ROS formation stage. However, based on the presented data, it is not possible to pinpoint whether NMDA receptor inhibition or the scavenging abilities are the dominant KYNA-mediated neuroprotective mechanisms.
Keyphrases
- cerebral ischemia
- oxidative stress
- reactive oxygen species
- dna damage
- subarachnoid hemorrhage
- brain injury
- blood brain barrier
- cell death
- ischemia reperfusion injury
- diabetic rats
- weight loss
- induced apoptosis
- bariatric surgery
- endothelial cells
- type diabetes
- anti inflammatory
- risk assessment
- big data
- machine learning
- heat shock
- weight gain
- human health
- deep learning
- gastric bypass