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

Tae-Kyeong Lee,Myoung Cheol Shin,Il-Jun Kang,Young Eun Park,Jun Hwi Cho,Moo-Ho Won,Bora Kim,Jae-Chul Lee,Go Eun Yang,Cheol Woo Park,Joon Ha Park,Ji Hyeon Ahn

doi:10.3390/md18010052

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.

Highlights

A transient brain ischemic insult, caused by temporary insufficiency of blood supply to the brain, inflicts ischemia-reperfusion injury to the brain [1,2]
In the vehicle/sham group, all hippocampal subfields were well stained by Cresyl Violet (CV) and pyramidal cells, which are located in the stratum pyramidale, were clearly detected by CV staining (Figure 1A,a)
In the vehicle/ischemia group, the distribution pattern of CV-stained cells was altered compared to the vehicle/sham group (Figure 1A,B)

Summary

Introduction

A transient brain ischemic insult, caused by temporary insufficiency of blood supply to the brain, inflicts ischemia-reperfusion injury to the brain [1,2]. Among these ischemic insults, transient forebrain ischemia (TFI) occurs due to the occlusion of both common carotid arteries and triggers selective neuronal death/loss in vulnerable subregions of the forebrain including the striatum, neocortex and hippocampus [3,4]. In response to the delayed neuronal death following TFI, glial cells (astrocytes and microglia) proliferate or undergo hypertrophy; this is known as “reactive gliosis” [3,7]. LA improves immune responses via promoting T- and B-cell and macrophage populations in leukemic mice [10]

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