Nutr Res Pract.  2017 Oct;11(5):381-387. 10.4162/nrp.2017.11.5.381.

Protection of the brain through supplementation with larch arabinogalactan in a rat model of vascular dementia

• Lim SH
• Lee J

• KMID: 2390130
• DOI: http://doi.org/10.4162/nrp.2017.11.5.381

Abstract

BACKGROUND/OBJECTIVES
Vascular dementia (VaD) caused by reduced blood supply to the brain manifests as white matter lesions accompanying demyelination and glial activation. We previously showed that arabinoxylan consisting of arabinose and xylose, and arabinose itself attenuated white matter injury in a rat model of VaD. Here, we investigated whether larch arabinogalactan (LAG) consisting of arabinose and galactose could also reduce white matter injury.
MATERIALS/METHODS
We used a rat model of bilateral common carotid artery occlusion (BCCAO), in which the bilateral common carotid arteries were exposed and ligated permanently with silk sutures. The rats were fed a modified AIN-93G diet supplemented with LAG (100 mg/kg/day) for 5 days before and 4 weeks after being subjected to BCCAO. Four weeks after BCCAO, the pupillary light reflex (PLR) was measured to assess functional consequences of injury in the corpus callosum (cc). Additionally, Luxol fast blue staining and immunohistochemical staining were conducted to assess white matter injury, and astrocytic and microglial activation, respectively.
RESULTS
We showed that white matter injury in the the cc and optic tract (opt) was attenuated in rats fed diet supplemented with LAG. Functional consequences of injury reduction in the opt manifested as improved PLR. Overall, these findings indicate that LAG intake protects against white matter injury through inhibition of glial activation.
CONCLUSIONS
The results of this study support our hypothesis that cell wall polysaccharides consisting of arabinose are effective at protecting white matter injury, regardless of their origin. Moreover, LAG has the potential for development as a functional food to prevent vascular dementia.

Keyword

Larix; hypoxia; carotid artery; white matter; functional food

MeSH Terms

Animals
Anoxia
Arabinose
Brain*
Carotid Arteries
Carotid Artery, Common
Cell Wall
Corpus Callosum
Dementia, Vascular*
Demyelinating Diseases
Diet
Functional Food
Galactose
Larix*
Models, Animal*
Optic Tract
Polysaccharides
Rats*
Reflex
Silk
Sutures
White Matter
Xylose
Arabinose
Galactose
Polysaccharides
Silk
Xylose

Figure

• 

  Fig. 1 A schematic diagram of the visual and pupillary light reflex (PLR) pathways. In the visual pathway, visual information reaching the retina passes through the optic nerve, optic tract (opt), and lateral geniculate nucleus (LGN) to the primary visual cortex (V1). In the PLR pathway, information for light intensity is mediated from the retina through the optic nerve, opt, pretectal nucleus, and oculomotor nerve to the pupillae muscle [22]. opt, optic tract.

• 

  Fig. 2 Luxol fast blue staining of myelin. (A). Experimental Scheme. LAG (100 mg/kg/day) was supplemented for 5 days before the rats underwent BCCAO surgery, and supplementation continued for another 4 weeks after surgery. In BCCAO surgery, the bilateral common carotid arteries in the control and LAG-treated groups were exposed and ligated permanently with silk sutures. The rats in the sham group underwent the same experimental procedure without ligation. The rats were then anesthetized again via isoflurane inhalation, after which their brains were harvested for Luxol fast blue staining and immunohistochemical staining. (B). Representative photomicrographs of selected white matter regions stained with Luxol fast blue (200×): (a), (d) sham group; (b), (e) control group; (c), (f) LAG-treated group; (a)–(c) and (d)–(f) were taken from the cc and opt, respectively. (C). Quantitative analysis of white matter injury. The extent of white matter injury in the cc and opt were graded as normal (Grade 0), disarrangement of nerve fibers (Grade 1), formation of marked vacuoles (Grade 2), and loss of myelinated fibers (Grade 3). The numbers of rats used in the sham, control and LAG-treated groups were 6, 6 and 6, respectively. ***P < 0.001, **P < 0.01 vs. control group. LAG, larch arabinogalactan; BCCAO, bilateral common carotid artery occlusion; cc, corpus callosum; opt, optic tract.

• 

  Fig. 3 Immunochemical staining of astrocytes. (A). Representative photomicrographs of astrocytes stained against GFAP with immunochemical techniques (100×): (a), (d) sham group; (b), (e) control group; (c), (f) LAG-treated group; (a)–(c) and (d)–(f) were taken from the cc and opt, respectively. (B). Quantitative analysis of GFAP-positive cells. The relative areas of GFAP-positive cells in the cc and opt were presented by setting the area of GFAP-positive cells for the sham group to 100%. The numbers of rats used in the sham, control and LAG-treated groups were 6, 6 and 6, respectively. **P < 0.01, *P < 0.05 vs. control group. GFAP, glial fibrillary acidic protein; LAG, larch arabinogalactan.

• 

  Fig. 4 Immunochemical staining of microglia. (A). Representative photomicrographs of microglia stained against Iba1 with immunochemical techniques (200×): (a) sham group; (b) control group; (c) LAG-treated group; (a)–(c) were taken from the opt. (B). Quantitative analysis of Iba1-positive cells. The relative numbers of Iba1-positive cells in the opt were presented by setting the number of Iba1-positive cells for the sham group at 100%. The numbers of rats used in the sham, control and LAG-treated groups were 6, 6 and 6, respectively. ***P < 0.001, **P < 0.01 vs. control group. LAG, larch arabinogalactan; opt, optic tract.

• 

  Fig. 5 A proposed pathway showing arabinose efficacy. When LAG is ingested, ara can be generated through acid hydrolysis in the stomach and through enzyme hydrolysis by microorganisms inhabiting the large intestine. The ara generated can then be absorbed into the body and penetrate across the BBB. Finally, ara in the brain reduces white matter injury in a rat BCCAO model. Modified from Ref. 16. LAG, larch arabinogalactan; ara, arabinose; BBB, blood-brain barrier; BCCAO, bilateral common carotid artery occlusion.

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