Behavioral deficits after distal focal cerebral ischemia in mice: Usefulness of adhesive removal test.

Abstract

Distal occlusion of the middle cerebral artery (dMCAo), which closely mimics human stroke, is one of the most used animal models. However, although assessment of histological and functional outcome is increasingly recommended for preclinical studies, the latter is often excluded because of the high difficulties to estimate, especially in mice, behavioral impairments. The aim of our study was to deeply screen functional consequences of distal permanent MCAo in mice to target relevant behaviors for future studies. A set of sensorimotor and cognitive tests were performed during 3 weeks postsurgery in 2 groups of mice. Afterward, brain infarctions were estimated by histological staining or magnetic resonance imaging. Overall, while no long-term functional impairments could be detected, the adhesive removal was the only test showing a deficit. Interestingly, this sensorimotor impairment was correlated to cortical damage 3 weeks after surgery. In conclusion, despite the fact that dMCAo-induced deficits could not be evidenced by most of our behavioral tests, the authors showed that the adhesive removal test was the only one, sensitive enough, to highlight a long-term deficit. This result suggests therefore that this mouse model of ischemia is relevant to efficiently assess therapeutic strategies with histological but also behavioral analysis, provided that relevant tests are used.

Cortical Selective Neuronal Loss, Impaired Behavior, and Normal Magnetic Resonance Imaging in a New Rat Model of True Transient Ischemic Attacks

“…Among several tests, only the SLT was affected in mice subjected to permanent distal MCAo. 32 Sensorimotor deficits after proximal MCAo more specifically reflect cortical relative to striatal damage. 12 This differential effect probably explains why in Sicard's 20 min proximal MCAo study, 8 where only marginal cortical SNL was present, impaired SLT had fully recovered before day 21, as compared with still recovering at day 28 here.…”

A Master Key to Assess Stroke Consequences Across Species: The Adhesive Removal Test

“…Additionally, sticking the adhesive tape on the forepaws of the animals will drive it to naturally remove the adhesive for its grooming. The same holds true for mice, in which adhesive test has been first described with positioning on the snout (Fleming et al, 2004), and then on forepaws Bouet et al, 2010;Bouet et al, 2007;Freret et al, 2009;Starkey et al, 2005), alike rats. In gerbils, and also in most of the studies performed in rats, the adhesive is placed on the wrist (Ishibashi et al, 2003).…”

“…Thus, beyond its effectiveness to highlight long term, and consequently tiny, sensory and motor deficit, the adhesive removal test is adaptable to several animal models, which is a fundamental advantage to translate animal research to clinical application. Convinced that this test could offer even more than it has already did, we will along this chapter give an overlook of the way it has to be performed and the results you may obtained in several animal models of stroke: mice, rats, and marmosets Bouet et al, 2010;Bouet et al, 2007;Freret et al, 2009;Freret et al, 2008;, i.e. the most used species in neuroscience research.…”

Improvements of the Stroke Model Guidelines Animal body weight and long-term functional concerns

“…neurological score (Bederson et al 1986), limb placing test (De Ryck et al 1989), chimney test, cylinder test (Bouet et al 2007)) -those tests would be mostly useful to assess acute phase after stroke, basically from 1 to 7 days) to more complex ones assessing both sensory and motor functions (i.e. adhesive removal , rotarod or staircase (Bouet et al 2007;Freret et al 2009;Freret et al 2006;Grabowski et al 1993;Modo et al 2000;Rogers et al 1997), which are conversely more relevant for long-term phase). Similarly, the memory tests have been developed to investigate cognitive functions (i.e.…”

“…Similarly, the memory tests have been developed to investigate cognitive functions (i.e. passive avoidance test, learning strategies -Morris water maze (Borlongan et al 1995;Bouet et al 2007;Freret et al 2009;Winter et al 2005) and would be preferentially used for later time points since they require minimal motor function). Stroke-induced functional impairments can be divided into acute (where the effect of drugs on the rate of recovery could be pointed out) and long-termed (where the effects of treatments on the extent of recovery could be appreciated).…”