Anti-apoptotic and anti-oxidative roles of quercetin after traumatic brain injury

Abstract

Experimental studies have demonstrated significant secondary damage (including cell apoptosis, blood-brain barrier disruption, inflammatory responses, excitotoxic damage, and free radical production) after traumatic brain injury (TBI). Quercetin is a natural flavonoid found in high quantities in fruits and vegetables, and may be a potential antioxidant and free radical scavenger. The purpose of this study was to determine the effects of quercetin on TBI-induced upregulation of oxidative stress, inflammation, and apoptosis in adult Sprague-Dawley rats. Animals were subjected to Feeney's weight-drop injury, thus inducing the parietal contusion brain injury model. Quercetin was administered (30 mg/kg intraperitoneal injection) 0, 24, 48, and 72 h after TBI. Quercetin reduced cognitive deficits, the number of TUNEL- and ED-1-positive cells, the protein expressions of Bax and cleaved-caspase-3 proteins, and the levels of TBARS and proinflammatory cytokines, and increased the activity of antioxidant enzymes (GSH-Px, SOD, and CAT) at 1 week after TBI. Our results suggest that in TBI rats, quercetin improves cognitive function owing to its neuroprotective action via the inhibition of oxidative stress, leading to a reduced inflammatory response, thereby reducing neuronal death.

Fig. 1

Escape latencies in the Morris water maze task were measured between 25 and 28 days, including the probe trials. *P < 0.05, **P < 0.01, *P < 0.001 versus the sham group, ^# P < 0.05, *P < 0.001 versus the saline group

Fig. 2

Levels of glutathione peroxidase (GSH-Px), thiobarbituric acid reactive substances (TBARS), catalase, and superoxide dismutase (SOD) in the injured cerebral cortex (the left hippocampus). *P < 0.05, **P < 0.01, ***P < 0.001 versus the sham group, ^# P < 0.05, ^## P < 0.01 versus the saline group

Fig. 3

Effects of quercetin on TBI-induced cell apoptosis. a Terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). TUNEL staining at the epicenter of the injured brain tissue (left hippocampus) in different experimental groups. b Quantitation of the number of the TUNEL-positive cells at the epicenter of the injured brain tissue (left hippocampus). c Representative bands of caspase-3 and Bax protein expression. d, e Band quantification for caspase-3 and Bax. **P < 0.01, ***P < 0.001, versus the sham group, ^# P < 0.05, ^## P < 0.01, ^### P < 0.001 versus the saline group. Scales bar (shown in a) = 100 μm

Fig. 4

Effect of quercetin on the presence of macrophages/activated microglia in TBI rats. ED-1 immunoreactivity in a sham-, b saline-, and c quercetin-treated groups. d Quantification of ED-1 immunoreactive cells in the injury epicenter of the brain tissue (the left hippocampus). *P < 0.05, **P < 0.01, ***P < 0.001, versus the sham group, ^# P < 0.05, ^## P < 0.01, vs the saline group. Scales bar (shown in a) = 75 μm