Abstract
Context: Hypoxic-ischemic encephalopathy (HIE) has a high morbidity and mortality rate. Resveratrol possesses numerous biological properties including antioxidant, anti-inflammatory and neuroprotective activities.Objective: The current experiment investigates the neuroprotective efficacy of resveratrol (RESV) against HIE by modulating Nrf2/HO-1 pathway in neonatal rats.Materials and methods: Seven-day-old pups (n = 48) were divided into four groups. Group-I rats receiving 2% DMSO saline (sham), group-II rats underwent unilateral carotid artery ligation and hypoxia (92% N2 and 8% O2) for 2.5 h (hypoxia-ischemia; HI), group-III and IV rats received 20 (RESV 20 + HI) or 40 mg/kg (RESV 40 + HI; group-IV) of RESV via intraperitoneal injection (ip), respectively, for 7 days prior to HI induction.Results: Pre-treatment with RESV (20 or 40) markedly reduced (p < 0.01) the cerebral oedema (86.23–71.26 or 65.24%), infarct area (33.85–19.81 or 14.30%), lipid peroxidation products, inflammatory markers [IL-1β 186–110 or 82; IL-6 255–146 or 103; TNF-α 310–204 or 137; NF-κB 205–115 or 91) p65 subunit] and significantly restored (p < 0.01) the antioxidative status by enhancing the activities of glutathione peroxidase (GPx) 5.22–6.49 or 7.78; catalase (CAT) 51–55 or 59, superoxide dismutase (SOD) 2.5–3.05 or 3.25; through marked upregulation (p < 0.01) of heme oxygenase 1 (HO-1) 0.65–0.69 or 0.73; and nuclear factor erythroid 2 related factor 2 (Nrf2) 0.73–0.86 or 0.91.Discussion and Conclusions: RESV displays its neurotherapeutic potential via upregulating the protein expression of Nrf2 and HO-1 signalling pathway and thereby attenuates oxidative stress and inflammatory response in HI-induced neonatal rats.
Highlights
Hypoxic-ischemic brain injury (HIBI) is the principal contributor to several types of neurological impairment (Long and Brandon 2007)
The nitrocellulose membrane was blocked with Tween 20, Tris-buffered saline solution (TBS) and 5% skimmed milk and incubated with primary antibody at 4 C for overnight
Antibodies employed for this study are as follows: Polyclonal rabbit anti-nuclear factor erythroid 2 related factor 2 (Nrf2) antibody (1:500 dilution; G921a Promega Corp., Madison, WI, USA), Polyclonal rabbit anti-heme oxygenase 1 (HO-1) antibody (1:800 dilution; CD143 Stressgen Biotechnologies, Victoria, BC, Canada) and rabbit polyclonal anti-rat b-actin (1:500 dilution; ZGB24 Zhongshan Goldenbridge Biotechnology, Beijing, China) or polyclonal anti
Summary
Hypoxic-ischemic brain injury (HIBI) is the principal contributor to several types of neurological impairment (Long and Brandon 2007). Every two newborns per 1000 full term births are affected by neonatal hypoxic-ischemic encephalopathy (HIE) (Kurinczuk et al 2010; Zhang et al 2016). The crucial pathophysiological event in HIE is the restriction of cerebral blood flow, which reduces oxygen supply to the brain cells and eventually leads to a collapsed electron transport chain (energy production) by a multifaceted cascade of biochemical events such as enhanced oxidant stress, inflammation, excitotoxicity and delayed cell death (Allen and Brandon 2011; Lu et al 2016). The present treatment regimen or procedures for HIE includes stem cell transplantation, anticonvulsants (anti-epileptic) drugs, and hypothermic treatments. The above mentioned treatment regimen or procedures are expensive and associated with few adverse effects (West et al 2007; Zanelli et al 2009)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
