hysiological and Biochemical Changes in NRF2 Pathway in Aged Animals Subjected to Brain Injury

Abstract

Background/Aims: Oxidative stress plays a key role in aging, which in turn represents a substantial risk factor for brain injuries. The aim of the present study was to investigate the differences in physiological and biochemical changes in the brain during injury-related inflammation and oxidative stress, comparing young and old mice. Methods: Young and old mice were subjected to focal cerebral ischemia induced by transient middle cerebral artery occlusion or to traumatic brain injury performed by a controlled cortical impactor. At the end of both experiments, mice were sacrificed 24h after injuries and brains were collected to perform biochemical analysis. Results: In both ischemic stroke and traumatic brain injury, aging has not only led to damage-induced worsening of motor function and behavioural changes but also increased of infarct area compared to young animals. Moreover, aged mice show increased evidence of oxidative stress and reduced antioxidant capacity when compared to younger animals, as demonstrated by Nrf2-Keap1 signalling pathway and lower expression of antioxidant enzymes, such as HO-1, SOD-1 and GSH-Px. Additionally, brain tissues collected from elderly mice showed an increased IκB-α degradation into the cytoplasm and consequently NF-κB translocation into the nucleus, compared to young mice subjected to same injuries. The elderly mice showed significantly higher levels of iNOS and CoX-2 expression than the young mice, as well as higher levels of inflammatory cytokines such as TNFα, IL-1β, and IL-6 after MCAO and TBI. Conclusion: Preserving and keeping the NRF-2 pathway active counteracts the onset of oxidative stress and consequent inflammation after ischemic and traumatic brain insult, particularly in the elderly. Not only that, NRF-2 pathway could represent a possible therapeutic target in the management of brain injuries.

Traumatic Brain Injury: An Age-Dependent View of Post-Traumatic Neuroinflammation and Its Treatment

“…Specifically, different microglial subtypes have been described as depending on age [ 127 , 128 ], presenting different characteristics and functions. Thus, as it has been suggested by some experimental studies [ 129 ], we could assume that the variation in the consequences of TBI due to age might depend on the variability of the inflammatory response. As Simon et al highlighted in their very exhaustive review on post-TBI neuroinflammation, “ there is a need to define the inflammatory phenotypes of our patients on the basis of injury characteristics such as patient age, sex, genetic predisposition, presence or absence of secondary insults, and serum, CSF and/or imaging biomarkers ” [ 130 ].…”

Hidrox® and Chronic Cystitis: Biochemical Evaluation of Inflammation, Oxidative Stress, and Pain

“…Hydrox ® , which contains 40-50% hydroxytyrosol, has been shown in our recent study to have hormetic properties and to induce the activation of the phase II enzyme responsible for antioxidant responses through the activation of the Nrf2/HO-1 pathway [25,44]. This pathway represents one of the antioxidant systems most involved in the maintenance of the intracellular redox state and, therefore, is widely studied for the prevention of numerous diseases caused by oxidative stress [45,46]. It is well-documented that CYP-induced cystitis induces an increase in oxidative stress and inflammation in the bladder [47,48].…”

Inhibition of P2X7 Purinergic Receptor Ameliorates Fibromyalgia Syndrome by Suppressing NLRP3 Pathway

“…The EPM test was performed on day 0 and 3, 5, 7 and 10 post first injection, as described previously [ 78 , 79 ], to measure anxiety-like behavior. The apparatus of the EPM consisted of two open arms and two closed arms (50 × 50 cm).…”

“…Rats were positioned in the middle of the apparatus and the number of entrances and time spent in the open arms were recorded in a five-minute duration using a video camera installed above the EPM [ 72 ]. Anxiety was indicated by a decrease in the proportion of time spent in the open arms and a decrease in the proportion of entries into the open arms [ 79 ].…”