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

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.

Estradiol Protects White Matter of Male C57BL6J Mice against Experimental Chronic Cerebral Hypoperfusion

“…As expected, our BCAS mice exhibited increased white matter injury and deficits in NOR testing when compared to their sham-operated counterparts (13, 76). Oral estradiol administration resulted in decreased white matter damage and fewer neurobehavioral deficits in the BCAS cohort, supporting a protective effect of estradiol.…”

Modelling physical resilience in ageing mice

“…Working memory deficits can be detected with the 8-arm radial maze test and Y maze test, at one to several months after BCAS establishment (Coltman et al, 2011; Maki et al, 2011). Deficits in recognition memory have also been reported (Patel et al, 2017). The most used coils of 0.18 mm decrease blood flow to 70% at two hours and it is partially recovered to 80% after one to three months.…”

Gradual common carotid artery occlusion as a novel model for cerebrovascular Hypoperfusion

“…Essentially all of the current paradigms involve the occlusion of two (Bottiger et al, 1998; Bottiger et al, 1999), three (Carmichael, 2005; Thal et al, 2010; Onken et al, 2012) or four (Pulsinelli and Buchan, 1988; Traystman, 2003) vessels. These paradigms include, bilateral common carotid artery stenosis (Shibata et al, 2007; Matin et al, 2016; Patel et al, 2017), permanent carotid artery ligation (Ohta et al, 1997) and sequential common carotid artery occlusion (Cechetti et al, 2010). Limitations of other procedures used to induce hypoperfusion in mice include a high mortality rate (Longa et al, 1989; Connolly et al, 1996; Kitagawa et al, 1998) and inconsistency in the severity and localization of cerebral damage (Connolly et al, 1996; Clark et al, 1997; Ohta et al, 1997; Takano et al, 1997; Matin et al, 2016; Patel et al, 2017).…”

“…These paradigms include, bilateral common carotid artery stenosis (Shibata et al, 2007; Matin et al, 2016; Patel et al, 2017), permanent carotid artery ligation (Ohta et al, 1997) and sequential common carotid artery occlusion (Cechetti et al, 2010). Limitations of other procedures used to induce hypoperfusion in mice include a high mortality rate (Longa et al, 1989; Connolly et al, 1996; Kitagawa et al, 1998) and inconsistency in the severity and localization of cerebral damage (Connolly et al, 1996; Clark et al, 1997; Ohta et al, 1997; Takano et al, 1997; Matin et al, 2016; Patel et al, 2017). Using the present paradigm, we were able to induce a consistent time-dependent reduction of cerebral blood flow that resulted in limited mortality and relatively conserved damage severity and localization.…”