Antioxidant Properties of Fucoidan Alleviate Acceleration and Exacerbation of Hippocampal Neuronal Death Following Transient Global Cerebral Ischemia in High-Fat Diet-Induced Obese Gerbils

Ji Ahn,Jong-Dai Kim,Joon Park,Jae-Chul Lee,Hyeyoung Kim,Myoung Shin,Moo-Ho Won,Hyunjung Kim,Tae-Kyeong Lee,Jun Cho,Soo Choi,Dae Kim,Young-Myeong Kim,Minah Song

doi:10.3390/ijms20030554

Abstract

Fucoidan, a natural sulfated polysaccharide, displays various biological activities including antioxidant properties. We examined the neuroprotective effect of fucoidan against transient global cerebral ischemia (tGCI) in high-fat diet (HFD)-induced obese gerbils and its related mechanisms. Gerbils received HFD for 12 weeks and fucoidan (50 mg/kg) daily for the last 5 days during HFD exposure, and they were subjected to 5-min tGCI. Pyramidal cell death was observed only in the CA 1 area (CA1) of the hippocampus in non-obese gerbils 5 days after tGCI. However, in obese gerbils, pyramidal cell death in the CA1 and CA2/3 occurred at 2 days and 5 days, respectively, after tGCI. In the obese gerbils, oxidative stress indicators (dihydroethidium, 8-hydroxyguanine and 4-hydroxy-2-nonenal) were significantly enhanced and antioxidant enzymes (SOD1 and SOD2) were significantly reduced in pre- and post-ischemic phases compared to the non-obese gerbils. Fucoidan treatment attenuated acceleration and exacerbation of tGCI-induced neuronal death in the CA1–3, showing that oxidative stress was significantly reduced, and antioxidant enzymes were significantly increased in pre- and post-ischemic phases. These findings indicate that pretreated fucoidan can relieve the acceleration and exacerbation of ischemic brain injury in an obese state via the attenuation of obesity-induced severe oxidative damage.

Highlights

Transient global cerebral ischemia occurs commonly during cardiac arrest or resuscitation, which hinders the supply of blood to the brain and causes the development of irreversible brain damage [1,2]
A crucial reason is that most animals used in experimental studies do not mimic the clinical state of patients with brain ischemia who generally have comorbidities, such as diabetes, hypertension, and obesity [31,32]
In this study, we set up an animal model of high-fat diet (HFD)-induced obesity to investigate neuroprotective effects of fucoidan against ischemic brain injury in animals with comorbidities, showing that the gerbils fed HFD for 12 weeks showed significant increases in body weight, blood glucose, serum triglyceride and total

Summary

Introduction

Transient global cerebral ischemia (tGCI) occurs commonly during cardiac arrest or resuscitation, which hinders the supply of blood to the brain and causes the development of irreversible brain damage [1,2]. Oxidative stress via excessive reactive oxygen species (ROS) production following tGCI has been considered as a major contributor to tGCI-induced DND [6,7]. Antioxidant therapy, which can effectively inhibit excessive production of ROS through the activation of endogenous antioxidant enzymes, is considered to be a potential therapeutic approach for tGCI-induced injury [8,9]. Obesity is known to cause the increase of oxidative stress in the brain [11]. Obesity induced by high-fat diet (HFD) results in exacerbated ischemic brain injury [14,15,16]. We must investigate protective strategies against ischemic brain injury in obesity

Objectives

Methods

Results

Conclusion