Pretreated fucoidan confers neuroprotection against transient global cerebral ischemic injury in the gerbil hippocampal CA1 area via reducing of glial cell activation and oxidative stress

• Published in: Biomedicine & pharmacotherapy Vol. 109; pp. 1718 - 1727
• Main Authors: Kim, Hyunjung, Ahn, Ji Hyeon, Song, Minah, Kim, Dae Won, Lee, Tae-Kyeong, Lee, Jae-Chul, Kim, Young-Myeong, Kim, Jong-Dai, Cho, Jun Hwi, Hwang, In Koo, Yan, Bing Chun, Won, Moo-Ho, Park, Joon Ha
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2019; Elsevier
• Subjects: Fucoidan; Neuroprotection; Oxidative stress; Resident glial cell; Superoxide dismutase; Transient global cerebral ischemia; DHE; NO; Neuroprotection; Oxidative stress; DDC; Superoxide dismutase; Fucoidan; tGCI; SOD2; LPS; GFAP; SOD1; CA1; NeuN; ROS; F–J; Transient global cerebral ischemia; Iba-1; HNE; Resident glial cell
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.11.015

[Display omitted] •Pretreatment with fucoidan protects CA1 pyramidal neurons from ischemic damage.•Pretreated fucoidan inhibits activation of glial cells in ischemic CA1 area.•Pretreated fucoidan attenuates oxidative stress in CA1 area after ischemic insult.•Pretreated fucoidan increases SODs expressions in ischemic CA1 pyramidal neurons.•Fucoidan-mediated neuroprotection is abolished by DDC (SODs inhibitor) treatment. Fucoidan is a sulfated polysaccharide derived from brown algae and possesses various beneficial activities, including antioxidant property. Previous studies have shown that fucoidan displays protective effect against ischemia-reperfusion injury in some organs. However, few studies have been reported regarding the protective effect of fucoidan against transient cerebral ischemic insults and its related mechanisms. Therefore, in this study, we examined the neuroprotective effect of fucoidan against transient global cerebral ischemia (tGCI), as well as underlying its mechanism using a gerbil model of tGCI which shows a loss of pyramidal neurons in the hippocampal cornu ammonis 1 (CA1) area after 5 min of tGCI. Fucoidan (25 and 50 mg/kg) was intraperitoneally administered once daily for 5 days before tGCI. Pretreatment with 50 mg/kg of fucoidan, not 25 mg/kg of fucoidan, attenuated tGCI-induced hyperactivity and protected CA1 pyramidal neurons from tGCI. In addition, pretreatment with 50 mg/kg of fucoidan inhibited activations of astrocytes and microglia in the ischemic CA1 area. Furthermore, pretreatment with 50 mg/kg of fucoidan significantly reduced the increased 4-hydroxy-2-noneal and superoxide anion radical production in the ischemic CA1 area and significantly increased expressions of SOD1 and SOD2 in the CA1 pyramidal neurons before and after tGCI. Additionally, treatment with diethyldithiocarbamate (an inhibitor of SODs) to the fucoidan-treated gerbils notably abolished the fucoidan-mediated neuroprotection. In brief, our present results indicate that fucoidan can effectively protect neurons from tGCI through attenuation of activated glial cells and reduction of oxidative stress via increase of SODs. Thus, we strongly suggest that fucoidan can be used as a useful preventive agent in cerebral ischemia.