J Vet Sci.  2018 Jul;19(4):505-511. 10.4142/jvs.2018.19.4.505.

Transient forebrain ischemia induces impairment in cognitive performance prior to extensive neuronal cell death in Mongolian gerbil (Meriones unguiculatus)

• Kondo T
• Yoshida S
• Nagai H
• Takeshita
• Mino M
• Morioka H
• Nakajima T
• Kusakabe K
• Okada T

• KMID: 2417565
• DOI: http://doi.org/10.4142/jvs.2018.19.4.505

Abstract

In Mongolian gerbils, bilateral common carotid artery occlusion (BCCAO) for several minutes induces ischemia, due to an incomplete circle of Willis, resulting in delayed neuronal cell death in the Cornet d'Ammon 1 (CA1) region of the hippocampus. Neuronal cell death in the hippocampus and changes in behavior were examined after BCCAO was performed for 5 min in the gerbils. One day after BCCAO, the pyramidal neurons of the CA1 region of the hippocampus showed degenerative changes (clumped chromatin in nuclei). At 5 and 10 days after BCCAO, extensive neuronal cell death was observed in the hippocampal CA1 region. Cognitive performance was evaluated by using the radial maze and passive avoidance tests. In the radial maze test, which examines win-stay performance, the number of errors was significantly higher in ischemic gerbils than in sham-operated gerbils on days 1 and 2 post-operation. In the passive avoidance test, the latency and freezing times were significantly shorter in ischemic gerbils than in sham-operated gerbils on the days 1, 2, and 4-6 post-operation. These results indicate that transient forebrain ischemia impairs cognitive performance, even immediately after the ischemic insult when there are only subtle signs of neuronal cell death.

Keyword

behavioral analysis; delayed neuronal cell death; forebrain ischemia; passive avoidance test; win-stay strategy

MeSH Terms

CA1 Region, Hippocampal
Carotid Artery, Common
Cell Death*
Chromatin
Circle of Willis
Freezing
Gerbillinae*
Hippocampus
Ischemia*
Neurons*
Prosencephalon*
Pyramidal Cells
Chromatin

Figure

• 

  Fig. 1 A schematic (A) and H&E-stained sections (B–F) of the hippocampus of gerbils. (A) Schematic of the hippocampus. The pyramidal cell layer of the CA1 (CA1) to CA3–CA4 (CA3–4) regions and the granular cell layer of the dentate gyrus (DG) are illustrated. (B) The CA1 region of a sham-operated gerbil in which pyramidal cells are densely distributed. (C) The CA1 region at 1 day after transient ischemia. Pale cytoplasm (white arrow), clumped chromatin (black arrows), and condensed nuclei (arrowhead) of pyramidal cells are present, and the inter-cell spaces are wider than those in the sham-operated group (panel B in Fig. 1). (D) The CA1 region at 3 days after ischemia. Pale cytoplasm (white arrows), clumped chromatin (black arrows), and condensed nuclei (arrowheads) of pyramidal cells are more frequent than at 1 day after transient ischemia (panel C in Fig. 1). (E) The CA1 region 5 days after ischemia. Condensed nuclei of pyramidal cells are more frequently seen than at 3 days after transient ischemia (panel D in Fig. 1). (F) The CA1 region 10 days after transient ischemia. Most of the cells in the pyramidal cell layer have condensed nuclei. CA1, Cornet d'Ammon 1. Scale bars = 50 µm (B–F).

• 

  Fig. 2 The number of errors made by bilateral common carotid artery occlusion-operated ischemic gerbils (▲) and sham-operated gerbils (●) in the radial maze test. *Significantly different from sham-operated gerbils (p < 0.05).

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