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. 2017 Oct;39(10):910-917.
doi: 10.1080/01616412.2017.1355423. Epub 2017 Aug 22.

Chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis causes selective recognition impairment in adult mice

Arati Patel  1   2 , Alimohammad Moalem  1 , Hank Cheng  2 , Robin M Babadjouni  1   2 , Kaleena Patel  1 , Drew M Hodis  2 , Deep Chandegara  1 , Steven Cen  1   3 , Shuhan He  1 , Qinghai Liu  2 , William J Mack  1   2   4
Affiliations

Chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis causes selective recognition impairment in adult mice

Arati Patel et al. Neurol Res. 2017 Oct.

Abstract

Objectives: Chronic cerebral hypoperfusion (CCH) can result in vascular dementia and small vessel white matter ischemic injury. These findings have previously been demonstrated in a murine experimental model of CCH secondary to bilateral common carotid artery stenosis (BCAS). This study sought to elucidate the effects of CCH on recognition memory as assessed by the novel object recognition (NOR) test and histological analysis of the hippocampus and perirhinal cortex.

Methods: Studies were performed on ten-week-old male mice using bilateral 0.18 mm microcoils to narrow the carotid arteries in accordance with prior publications. Following surgery, BCAS (n = 6) and sham (n = 6) mice were evaluated using NOR and 8-arm radial maze testing paradigms. Tissue damage was assessed using H&E staining on a parallel cohort of mice (n = 6 BCAS, n = 7 sham).

Results: In the NOR paradigm, BCAS mice demonstrated significant deficits in short-term memory. Consistent with prior studies, BCAS mice also performed significantly worse on 8-arm radial maze testing. BCAS mice exhibited significantly more neuronal injury in the perirhinal cortex when compared to sham-operated mice. However, no significant differences in neuronal damage were observed in the CA1 region of the hippocampus.

Discussion: Experimental CCH secondary to BCAS results in recognition memory deficits on NOR testing. Damage to the perirhinal cortex, rather than to the hippocampus, may underlie this impairment.

Keywords: Ischemia; hypoperfusion; novel object recognition; perirhinal cortex; short-term memory.

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Conflict of interest statement

Disclosure statement

No potential conflict of interest was reported by the authors.

Figures

Figure 1
Figure 1
Eight-Arm Radial Maze Performance. (a) Pictorial representation of mice performance on the 8-arm radial maze during the first blocked trial. Left: Sham, Right: BCAS. (b) Pictorial representation of mice performance on the 8-arm radial maze during the eighth blocked final trial. Left: Sham, Right: BCAS. (c) BCAS mice did not have significantly different maze completion times compared to shams (p > 0.05). Both BCAS and sham mice significantly reduced their time to complete the maze over time (p < 0.001). (d) BCAS mice committed significantly more re-entry errors compared to the sham (F(1,10) = 18.285; p < 0.01). Both groups made significantly fewer errors over the course of training (p < 0.001). (e) Within the first 8-arm choices, BCAS mice selected significantly fewer novel entries compared to shams (F(1,10) = 4.976; p < 0.05). Sham mice exhibited a linear trend of improvement in novel entries as trials progressed, however BCAS mice exhibited a diminished learning effect as the trials progressed (p < 0.05).
Figure 2
Figure 2
Assessment of long-term and short-term memory performance on novel object recognition test. (a) The discrimination index for NOR short-term memory test was significantly lower in BCAS mice compared to shams. The total object exploration time of the novel object (Nov) was significantly longer than the familiar object (Fam) in both groups. BCAS mice explored the novel object less frequently that the sham mice, although was not significant using the interaction test (p = 0.11) (b) The discrimination index for NOR long-term memory test did not differ between BCAS and sham mice. Notes: Sham mice explored the novel object significantly longer than the familiar object. However, BCAS mice did not explore the novel object longer than the familiar object. n = 6 mice/group, *Signifies p < 0.05, **Signifies p < 0.001, ***Signifies p < 0.0001.
Figure 3
Figure 3
Histology scores for neuronal damage in perirhinal cortex and CA1 hippocampus. (a) Representative H&E staining for ischemic damage on the perirhinal cortex. Left: Sham, Right: BCAS (b) Perirhinal cortex from BCAS mice showed significantly more neuronal damage compared to sham. Notes: CA1 region of the hippocampus showed no differences between BCAS and sham mice. *Signifies p < 0.05. Scale bar = 30 μm. n = 7 sham mice, 6 BCAS mice.
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