Pre-Treatment with Laminarin Protects Hippocampal CA1 Pyramidal Neurons and Attenuates Reactive Gliosis Following Transient Forebrain Ischemia in Gerbils

Abstract

Transient brain ischemia triggers selective neuronal death/loss, especially in vulnerable regions of the brain including the hippocampus. Laminarin, a polysaccharide originating from brown seaweed, has various pharmaceutical properties including an antioxidant function. To the best of our knowledge, few studies have been conducted on the protective effects of laminarin against ischemic injury induced by ischemic insults. In this study, we histopathologically investigated the neuroprotective effects of laminarin in the Cornu Ammonis 1 (CA1) field of the hippocampus, which is very vulnerable to ischemia-reperfusion injury, following transient forebrain ischemia (TFI) for five minutes in gerbils. The neuroprotective effect was examined by cresyl violet staining, Fluoro-Jade B histofluorescence staining and immunohistochemistry for neuronal-specific nuclear protein. Additionally, to study gliosis (glial changes), we performed immunohistochemistry for glial fibrillary acidic protein to examine astrocytes, and ionized calcium-binding adaptor molecule 1 to examine microglia. Furthermore, we examined alterations in pro-inflammatory M1 microglia by using double immunofluorescence. Pretreatment with 10 mg/kg laminarin failed to protect neurons in the hippocampal CA1 field and did not attenuate reactive gliosis in the field following TFI. In contrast, pretreatment with 50 or 100 mg/kg laminarin protected neurons, attenuated reactive gliosis and reduced pro-inflammatory M1 microglia in the CA1 field following TFI. Based on these results, we firmly propose that 50 mg/kg laminarin can be strategically applied to develop a preventative against injuries following cerebral ischemic insults.

Effects of Recombinant Spidroin rS1/9 on Brain Neural Progenitors After Photothrombosis-Induced Ischemia

“…On the other hand, as a result of ischemic damage to the prefrontal cortex, the levels of GFAP increased, which may indicate the development of astrogliosis. Previously, remote cortical damage in the sensorimotor or prefrontal region has been shown to cause the proliferation of reactive astrocytes (Sandhir et al, 2008;Chin et al, 2013;Lee et al, 2020). Our results are also consistent with data from Gao and coauthors, who showed an increase in GFAP + cells in the granule cell layer and hilus zone (Gao et al, 2009) in a similar mouse line during TBI modeling.…”

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

“…Regarding the case of inflammation, Neyrinck et al (2007) showed that laminarin protected against LPS-induced hepatotoxicity in rats via a decrease in the serum monocyte number, nitrite, and TNFα. Additionally, we recently reported that laminarin pretreatment strongly attenuated activations of astrocytes and microglia in the hippocampal CA1 after brain IR in gerbils [28]. Thus, together with our and other previous studies, our current findings potentially suggest that alleviation of oxidative stress and neuroinflammation in the ischemic hippocampal CA1 of aged gerbils by pretreatment with laminarin contributes to neuroprotection against IR injury.…”

“…Pretreated fucoidan, for example, significantly reduces cerebral infarction size following transient focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO)in adult rats [25] and protects pyramidal neurons in the hippocampal CA1 from IR injury in an adult gerbil model of transient global forebrain ischemia [27]. Furthermore, we recently reported that laminarin pretreatment had a strong neuroprotection in the hippocampal CA1 against IR injury in an adult gerbil model of transient global forebrain ischemia [28]. However, the above-mentioned studies were done in adult animal models; these studies have a limitation in not addressing ischemic insults in the aged population with a higher risk of ischemic stroke.…”

“…The gerbils in the experimental groups were sacrificed at 1 day and 5 days after IR surgery. The dosage and duration of laminarin (Sigma-Aldrich, Poole, Dorset, UK) treatment were selected based on the results of our previous study [28]. The vehicle and laminarin were administered intraperitoneally once a day for 7 consecutive days before IR.…”

“…Fucoidan, for example, a type of polysaccharide extracted from various species of brown algae, shows strong neuroprotective effects against ischemic brain injury in animal models of brain ischemia [24][25][26][27]. Additionally, we recently reported that laminarin, a water-soluble polysaccharide derived from the brown algae Laminaria digitate, showed neuroprotection against IR brain injury in adult gerbils [28]. Laminarin exhibits biofunctional properties, such as anti-apoptotic [29], anti-oxidant [30], anti-inflammatory [31], and anti-cancer [32] activities.…”