Korean J Physiol Pharmacol.  2008 Jun;12(3):89-94. 10.4196/kjpp.2008.12.3.89.

White Matter Damage and Hippocampal Neurodegeneration Induced by Permanent Bilateral Occlusion of Common Carotid Artery in the Rat: Comparison between Wistar and Sprague-Dawley Strain

• Kim SK
• Cho KO
• Kim SY

• KMID: 2285348
• DOI: http://doi.org/10.4196/kjpp.2008.12.3.89

Abstract

In order to reproduce chronic cerebral hypoperfusion as it occurs in human aging and Alzheimer's disease, we introduced permanent, bilateral occlusion of the common carotid arteries (BCCAO) in rats (Farkas et al, 2007). Here, we induced BCCAO in two different rat strains in order to determine whether there was a strain difference in the pathogenic response to BCCAO. Male Wistar and Sprague-Dawley (SD) rats (250-270 g) were subjected to BCCAO for three weeks. Kluver-Barrera and cresyl violet staining were used to evaluate white matter and gray matter damage, respectively. Wistar rats had a considerably higher mortality rate (four of 14 rats) as compared to SD rats (one of 15 rats) following BCCAO. Complete loss of pupillary light reflex occurred in all Wistar rats that survived, but loss of pupillary light reflex did not occur at all in SD rats. Moreover, BCCAO induced marked vacuolation in the optic tract of Wistar rats as compared to SD rats. In contrast, SD rats showed fewer CA1 hippocampal neurons than Wistar rats following BCCAO. These results suggest that the neuropathological process induced by BCCAO takes place in a region-specific pattern that varies according to the strain of rat involved.

Keyword

Chronic cerebral hypoperfusion; Wistar strain; Sprague-Dawley strain; White matter damage; Hippocampal neurodegeneration; Rat

MeSH Terms

Aging
Alzheimer Disease
Animals
Benzoxazines
Carotid Artery, Common
Humans
Hypogonadism
Light
Male
Mitochondrial Diseases
Neurons
Ophthalmoplegia
Rats
Rats, Wistar
Reflex
Sprains and Strains
Viola
Visual Pathways
Benzoxazines
Hypogonadism
Mitochondrial Diseases
Ophthalmoplegia

Figure

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  Fig. 1. The difference in weight gain between Wistar and Sprague-Dawley (SD) rats after bilateral common carotid artery occlusion (BCCAO). Wistar rats failed to catch up to the weights of sham-operated animals during 21 days of BCCAO. Data reported are means ± SD. ∗p<0.05 by one-way ANOVA.

• 

  Fig. 2. Klüver-Barrera staining for white matter damage after 21 days of bilateral common carotid artery occlusion (BCCAO). Schematic representation of the rat optic tract (A). The rectangle identifies the section of the optic tract evaluated in this study (B-E). Sections were taken from (2.92 mm relative to bregma in the anteroposterior plane (adapted from Paxinos and Watson, 2007). Optic tract of Sprague-Dawley (SD) rats subjected to sham operation (B) or BCCAO (D). Optic tract of Wistar rats subjected to sham operation (C) or BCCAO (E). Note that BCCAO caused more serious white matter damage in the optic tract of Wistar rats than in that of SD rats. Scale bar=50μm.

• 

  Fig. 3. Cresyl violet staining of the hippocampal CA1 damage after 21 days of bilateral common carotid artery occlusion (BCCAO). Hippocampal CA1 lesion of Sprague-Dawley (SD) rats subjected to sham operation (A) or BCCAO (B). Hippocampal CA1 region of Wistar rats subjected to sham operation (C) or BCCAO (D). Schematic representation of the rat hippocampal CA1 region (E, adapted from Paxinos and Watson, 2007). The rectangle indicates the area of the brain that was examined in this study. The number of cells in the hippocampal CA1 region in SD and Wistar rats subjected to sham operation or BCCAO (F). Note that BCCAO induced significantly more pyramidal neuronal damage in CA1 subfield of the hippocampus of SD rats than in that of Wistar rats. There was no difference in the number of CA1 pyramidal neurons between sham-operated and BCCAO-induced Wistar rats. The data shown are the mean number of intact pyramidal neurons (± SD). Scale bar in A-D = 50μ m. ∗p<0.05 by one-way ANOVA.

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