TY  - JOUR
AU  - Skrobot, Matej
AU  - Sa, Rafael De
AU  - Walter, Josefine
AU  - Vogt, Arend
AU  - Paulat, Raik
AU  - Lips, Janet
AU  - Mosch, Larissa
AU  - Mueller, Susanne
AU  - Dominiak, Sina
AU  - Sachdev, Robert
AU  - Boehm-Sturm, Philipp
AU  - Dirnagl, Ulrich
AU  - Endres, Matthias
AU  - Harms, Christoph
AU  - Wenger, Nikolaus
TI  - Refined movement analysis in the staircase test reveals differential motor deficits in mouse models of stroke.
JO  - Journal of cerebral blood flow & metabolism
VL  - 44
IS  - 9
SN  - 0271-678X
CY  - London
PB  - Sage
M1  - DZNE-2024-01114
SP  - 1551 - 1564
PY  - 2024
AB  - Accurate assessment of post-stroke deficits is crucial in translational research. Recent advances in machine learning offer precise quantification of rodent motor behavior post-stroke, yet detecting lesion-specific upper extremity deficits remains unclear. Employing proximal middle cerebral artery occlusion (MCAO) and cortical photothrombosis (PT) in mice, we assessed post-stroke impairments via the Staircase test. Lesion locations were identified using 7 T-MRI. Machine learning was applied to reconstruct forepaw kinematic trajectories and feature analysis was achieved with MouseReach, a new data-processing toolbox. Lesion reconstructions pinpointed ischemic centers in the striatum (MCAO) and sensorimotor cortex (PT). Pellet retrieval alterations were observed, but were unrelated to overall stroke volume. Instead, forepaw slips and relative reaching success correlated with increasing cortical lesion size in both models. Striatal lesion size after MCAO was associated with prolonged reach durations that occurred with delayed symptom onset. Further analysis on the impact of selective serotonin reuptake inhibitors in the PT model revealed no clear treatment effects but replicated strong effect sizes of slips for post-stroke deficit detection. In summary, refined movement analysis unveiled specific deficits in two widely-used mouse stroke models, emphasizing the value of deep behavioral profiling in preclinical stroke research to enhance model validity for clinical translation.
KW  - Animals
KW  - Mice
KW  - Disease Models, Animal
KW  - Male
KW  - Infarction, Middle Cerebral Artery: diagnostic imaging
KW  - Infarction, Middle Cerebral Artery: physiopathology
KW  - Infarction, Middle Cerebral Artery: complications
KW  - Stroke: physiopathology
KW  - Stroke: diagnostic imaging
KW  - Stroke: complications
KW  - Mice, Inbred C57BL
KW  - Magnetic Resonance Imaging: methods
KW  - Machine Learning
KW  - Movement: physiology
KW  - Machine learning (Other)
KW  - motor deficits (Other)
KW  - rodent models (Other)
KW  - stroke (Other)
KW  - translational research (Other)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11418716
C6  - pmid:39234984
DO  - DOI:10.1177/0271678X241254718
UR  - https://pub.dzne.de/record/271972
ER  -