Neuroprotective Role of Nanoencapsulated Quercetin in Combating Ischemia-Reperfusion Induced Neuronal Damage in Young and Aged Rats

Abstract

Cerebral stroke is the leading cause of death and permanent disability among elderly people. In both humans and animals, cerebral ischemia damages the nerve cells in vulnerable regions of the brain, viz., hippocampus, cerebral cortex, cerebellum, and hypothalamus. The present study was conducted to evaluate the therapeutic efficacy of nanoencapsulated quercetin (QC) in combating ischemia-reperfusion-induced neuronal damage in young and aged Swiss Albino rats. Cerebral ischemia was induced by occlusion of the common carotid arteries of both young and aged rats followed by reperfusion. Nanoencapsulated quercetin (2.7 mg/kg b wt) was administered to both groups of animals via oral gavage two hours prior to ischemic insults as well as post-operation till day 3. Cerebral ischemia and 30 min consecutive reperfusion caused a substantial increase in lipid peroxidation, decreased antioxidant enzyme activities and tissue osmolality in different brain regions of both groups of animals. It also decreased mitochondrial membrane microviscosity and increased reactive oxygen species (ROS) generation in different brain regions of young and aged rats. Among the brain regions studied, the hippocampus appeared to be the worst affected region showing increased upregulation of iNOS and caspase-3 activity with decreased neuronal count in the CA1 and CA3 subfields of both young and aged rats. Furthermore, three days of continuous reperfusion after ischemia caused massive damage to neuronal cells. However, it was observed that oral treatment of nanoencapsulated quercetin (2.7 mg/kg b wt) resulted in downregulation of iNOS and caspase-3 activities and improved neuronal count in the hippocampal subfields even 3 days after reperfusion. Moreover, the nanoformulation imparted a significant level of protection in the antioxidant status in different brain regions, thus contributing to a better understanding of the given pathophysiological processes causing ischemic neuronal damage.

Hypoxia/Reoxygenation Stress Signals an Increase in Organic Anion Transporting polypeptide 1a4 (Oatp1a4) at the Blood–Brain Barrier: Relevance to CNS Drug Delivery

“…5,29 The molecular weights of resulting PARP fragments are indicative of participation of a specific protease. Consistent with previous findings, 30 we found elevated cleaved-to-uncleaved PARP ratios in whole-brain lysates prepared from animals subjected to hypoxic insult (1 hour, 6% O 2 ) and reoxygenated for 10 minutes, 30 minutes, and 1 hour as compared with these same ratios in brain lysates from normoxic animals ( Figures 1A and 1B). The PARP fragments detected (i.e., 89 kDa) were consistent with those produced by executioner caspases.…”

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

“…194 Nanosizing quercetin greatly increases bioavailability and increases the protective effect at the target site without much loss in the gastrointestinal tract during oral administration. 98,135,[195][196][197] Oral delivery of nanoencapsulated quercetin with a size of 270 nm protects rat brain and liver cells from toxicity induced by arsenic. These studies have confirmed that quercetin is highly protected in the gastrointestinal tract and can be safely delivered to the target site in the brain.…”

Neuroprotective effects of quercetin in a mouse model of brain ischemic/reperfusion injury via anti-apoptotic mechanisms based on the Akt pathway

“…It was reported that quercetin was able to maintain blood-brain barrier integrity by scavenging active oxygen (4). It was suggested that oral treatment with quercetin nanocapsules may exert a protective effect against oxidative damage and prevent pyramidal neurons in the hippocampus from ischemia/reperfusion (I//R) (5). However, the exact mechanism of the neuroprotective effect of quercetin against global brain I/R injury has remained elusive.…”