Laminarin Pretreatment Provides Neuroprotection against Forebrain Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Neuroinflammation in Aged Gerbils

Abstract

Laminarin is a polysaccharide isolated from brown algae that has various biological and pharmacological activities, such as antioxidant and anti-inflammatory properties. We recently reported that pretreated laminarin exerted neuroprotection against transient forebrain ischemia/reperfusion (IR) injury when we pretreated with 50 mg/kg of laminarin once a day for seven days in adult gerbils. However, there have been no studies regarding a neuroprotective effect of pretreated laminarin against IR injury in aged animals and its related mechanisms. Therefore, in this study, we intraperitoneally inject laminarin (50 mg/kg) once a day to aged gerbils for seven days before IR (5-min transient ischemia) surgery and examine the neuroprotective effect of laminarin treatment and the mechanisms in the gerbil hippocampus. IR injury in vehicle-treated gerbils causes loss (death) of pyramidal neurons in the hippocampal CA1 field at five days post-IR. Pretreatment with laminarin effectively protects the CA1 pyramidal neurons from IR injury. Regarding the laminarin-treated gerbils, production of superoxide anions, 4-hydroxy-2-nonenal expression and pro-inflammatory cytokines [interleukin(IL)-1β and tumor necrosis factor-α] expressions are significantly decreased in the CA1 pyramidal neurons after IR. Additionally, laminarin treatment significantly increases expressions of superoxide dismutase and anti-inflammatory cytokines (IL-4 and IL-13) in the CA1 pyramidal neurons before and after IR. Taken together, these findings indicate that laminarin can protect neurons from ischemic brain injury in an aged population by attenuating IR-induced oxidative stress and neuroinflammation.

Brain Factor-7® improves learning and memory deficits and attenuates ischemic brain damage by reduction of ROS generation in stroke in vivo and in vitro

“…For example, a previous study showed that aqueous extract from Scrophulariae Radix, which belongs to Scrophulariaceae family, ameliorated infarct lesion in the brain of a rat model of MCAO via regulation of mitogen-activated protein kinase pathway [ 28 ]. In addition, we reported that laminarin and fucoidan, which are brown algae-derived polysaccharides, exerted neuroprotective effects against 5-min transient forebrain ischemia in gerbils through their antioxidant efficacy [ 29 , 30 ]. To the best of our knowledge, even though various natural resources display neuroprotective effects, the neuroprotective effect of cocoon hydrate such as BF-7 against ischemic insults has been poorly investigated.…”

Laminarin Attenuates Ultraviolet-Induced Skin Damage by Reducing Superoxide Anion Levels and Increasing Endogenous Antioxidants in the Dorsal Skin of Mice

“…It has been reported that UVB exposure induces the production of reactive oxygen species (ROS), such as superoxide radical and hydroxyl, and upregulates the intracellular signaling pathways mediated by epidermal growth factor receptor (EGFR) and transcription factors (nuclear factors AP-1 and NF-κB), which activate MMPs, block collagen gene expression and activate keratinocyte proliferation [29]. In this study, we evaluated the production of ROS induced by UVB exposure via DHE histofluorescence staining, which is a useful indicator of the in situ generation of superoxide anion [30]. In our present study, we found a significant increase in superoxide anion production in the skin of the UVB group.…”

“…In rat muscles, LA treatment decreases lipid peroxidation in blood and increases antioxidant levels in the muscles after rigorous exercise in rats [35]. In gerbil hippocampus, after transient cerebral ischemia, LA treatment attenuated superoxide anion generation and lipid peroxidation by increasing the expression of SOD1 and SOD2 [30]. In a rat model of sepsis, LA treatment reduces lipid peroxidation in the lung by maintaining CAT and increasing SOD, GPx and CAT concentration [36].…”

“…To detect an intracellular superoxide anion, the tissues sections were stained with DHE (Sigma-Aldrich, St. Louis, MO, USA), which is a well-known fluorogenic probe. In short, according to previously published studies [30,45], the sections were equilibrated in Krebs-HEPES buffer (composed of 130 mM NaCl, 5.6 mM KCl, 2 mM CaCl 2 , 0.24 mM MgCl 2 , 8.3 mM HEPES, 11 mM glucose, pH 7.4, etc. ), for 40 min at 37 • C. Fresh buffer containing DHE (10 µmol/L) was applied on the sections for 2 h at 37 • C, and DHE was oxidized on reaction with superoxide to fluorescent molecule ethidium bromide, which binds DNA in nuclei.…”

“…Oxidative stress was analyzed based on the relative fluorescence intensity of DHE, briefly, as described previously by [30]. In brief, digital images of the stained sections were captured with a fluorescence microscope (BX53) (Olympus, Tokyo, Japan), equipped with the excitation wavelength of 520-540 nm.…”