Nest‐building activity as a reproducible and long‐term stroke deficit test in a mouse model of stroke

INTRODUCTION: Neuroprotective therapeutics achieved from animal studies have not been able to translate into clinical stroke therapies. A major reason may be that the functional tests and outcomes between animal stroke studies and clinical trials are significantly different. Ultimately, functional recovery is most important for stroke patients, but it remains challenging to identify animal functional tests that reflect human stroke deficits. This study aimed to explore whether the nest‐building activity can be used as a functional test of mouse stroke deficit. METHODS: Forty‐one C57B6 male mice were randomly assigned into a sham‐operated control group and 20‐, 40‐ and 60‐min middle cerebral artery occlusion (MCAO) groups. Mice were perfusion‐fixed at 21 days following sham surgery or MCAO. Infarct volumes were assessed under the light microscopy. The nest‐building activity was characterized and quantitatively evaluated. RESULTS: The results show that only a small portion of striatum was damaged after 20‐min MCAO. The brain damage areas were expanded from striatum to the neocortex and hippocampus proportionally after 40‐min and 60‐min MCAO, respectively. Consistently, relative to that of the sham‐operated mice, the nest‐building activity was insignificantly altered after 20‐min MCAO, but dramatically and significantly reduced proportionally following 40‐min and 60‐min MCAO, respectively. The nest‐building deficit was a long‐lasting event and could be seen for as long as 14‐21 days of recovery, the longest endpoint of this study. CONCLUSIONS: The results suggest that the nest‐building activity may be a novel, objective, easy to use, highly sensitive, and long‐lasting test that may reflect the multifaceted sensorimotor and cognitive deficits after stroke in humans. Our findings may provide a novel multifaceted test for bridging the gap between animal stroke studies and clinical trials.