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

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.

Freret T ，Bouet V ，Leconte C ，Roussel S ，Chazalviel L ，Divoux D ，Schumann-Bard P ，Boulouard M ... -  《BEHAVIORAL NEUROSCIENCE》

Sensorimotor and cognitive deficits after transient middle cerebral artery occlusion in the mouse.

Bouët V ，Freret T ，Toutain J ，Divoux D ，Boulouard M ，Schumann-Bard P ... -  《EXPERIMENTAL NEUROLOGY》

Long-term functional outcome following transient middle cerebral artery occlusion in the rat: correlation between brain damage and behavioral impairment.

The assessment of both histological and functional long-term outcomes after cerebral ischemia is increasingly recommended for preclinical studies. Whereas correlations between behavioral impairments and primary ischemic lesion are documented, little is known about their relationships with remote nonischemic regions that undergo secondary degeneration, such as the thalamus. Anesthetized rats were subjected to mild (30 min) or severe (60 min) occlusion of the middle cerebral artery. Two months after ischemia, sensorimotor behavior was assessed according to the neurological score, limb-placing, adhesive-removal, and staircase tests; the final histological lesion was measured after this assessment. Cortical damage was correlated to all transient and long-lasting sensorimotor deficits, whereas striatal lesion was more consistently reflected by the forelimb-placing reflexes and adhesive-removal motor deficits. By contrast, the thalamic atrophy was not correlated to early neurological impairment, but rather to the late sensory deficit at the adhesive-removal test and to the skilled forepaw reaching alteration at the staircase test. This suggests that thalamus contributes, albeit moderately, to the ischemia-induced long-lasting sensorimotor deficits, some of which represent relevant targets for therapeutic interventions.

Freret T ，Chazalviel L ，Roussel S ，Bernaudin M ，Schumann-Bard P ，Boulouard M ... -  《BEHAVIORAL NEUROSCIENCE》

Human umbilical cord blood cells do not improve sensorimotor or cognitive outcome following transient middle cerebral artery occlusion in rats.

Mäkinen S ，Kekarainen T ，Nystedt J ，Liimatainen T ，Huhtala T ，Närvänen A ，Laine J ，Jolkkonen J ... -  《BRAIN RESEARCH》

Deficits in auditory, cognitive, and motor processing following reversible middle cerebral artery occlusion in mice.

Middle cerebral artery occlusion(1) (MCAO) is a widely used experimental technique in rodents to model both the short-term pathological events and longer term neuroanatomical and functional damage associated with focal ischemia. Various neurobehavioral tasks have been developed to assess the motor and cognitive dysfunctions associated with MCAO in rodents, and these studies have revealed deficits related to long-term sensorimotor function, as well as retention of spatial memory. Assessment of auditory processing in a MCAO model has not been undertaken, despite findings suggesting an auditory processing deficit in humans with stroke induced-aphasia, a common post-stroke deficit. Using a modified pre-pulse inhibition paradigm, and other behavioral tasks thought to tap "language-related processing", adult male C57Bl/6 mice were subjected to 60 minute MCAO or Sham surgery and were behaviorally assessed from P58 to P124 (2 to 65 days post-surgery). Tasks were selected based on evidence that rapid auditory processing(2) (RAP) skills are associated with language processing indices in clinical populations. Cognitive and sensorimotor ability was evaluated using the Morris water maze, non-spatial water maze, and a post-injury rotarod task administered over multiple days (motor learning). Combined behavioral results from post-MCAO mice provide evidence of a RAP deficit as well as deficits in spatial, non-spatial, and motor learning. Overall results support a fuller characterization of behavioral deficits in auditory processing after MCAO.

Truong DT ，Venna VR ，McCullough LD ，Fitch RH ... -  《-》