The CatWalk XT® is a valid tool for objective assessment of motor function in the acute phase after controlled cortical impact in mice

Walter, Johannes; Kovalenko, Olga; Younsi, Alexander; Grutza, Martin; Unterberg, Andreas; Zweckberger, Klaus

doi:10.1016/j.bbr.2020.112680

Cited by 23 publications

(14 citation statements)

References 48 publications

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“…In the current study we could show that CCI with the chosen parameters leads to diffuse bilateral impairments of static as well as dynamic CatWalk XT ® parameters in the acute phase after CCI in mice (Figs 4 – 7 ). This is well in line with multiple previous studies and might in part be explained by the fact, that many lesions extended to the corpus callosum in our current experiments [ 16 , 34 – 36 ]. However, impairments of many static parameters including paw prints and paw intensities nearly completely resolved within the first week after trauma induction and were no longer detectable at two and four weeks after CCI (Figs 4 and 5 ).…”

Section: Discussionsupporting

confidence: 94%

“…While the CatWalkXT ® ’s value in gait assessment in experimental models of spinal cord injury and peripheral nerve injury has been well documented, it’s value in the context of gait assessment in preclinical TBI in rodents remained unclear. However, in a previous study, we recently validated the CatWalkXT ® as an excellent rater independent automated test of gait and motor function in the acute phase after CCI in mice, identifying it as an excellent tool for testing these domains of neurobehavioral function specifically in the CCI model in rodents [ 16 ]. Yet, it remains unclear if there is a robust correlation between structural damage and gait and motor function after experimental TBI in mice and thus, if the effects of a treatment can be thoroughly evaluated focusing on histological outcome parameters or if more focus should be directed towards neurobehavioral testing in preclinical TBI studies.…”

Section: Introductionmentioning

confidence: 99%

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Focal lesion size poorly correlates with motor function after experimental traumatic brain injury in mice

et al. 2022

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Background It remains unclear whether neurobehavioral testing adds significant information to histologic assessment of experimental traumatic brain injury (TBI) and if automated gait assessment using the CatWalk XT®, while shown to be effective in in the acute phase, is also effective in the chronic phase after experimental TBI. Therefore, we evaluated the correlation of CatWalk XT® parameters with histologic lesion volume and analyzed their temporal and spatial patterns over four weeks after trauma induction. Methods C57Bl/6 mice were subjected to controlled cortical impact (CCI). CatWalk XT® analysis was performed one day prior to surgery and together with the histological evaluation of lesion volume on postoperative days one, three, seven, 14 and 28. Temporal and spatial profiles of gait impairment were analyzed and a total of 100 CatWalk XT® parameters were correlated to lesion size. Results While in the first week after CCI, there was significant impairment of nearly all CatWalk XT® parameters, impairment of paw prints, intensities and dynamic movement parameters resolved thereafter; however, impairment of dynamic single paw parameters persisted up to four weeks. Correlation of the CatWalk XT® parameters with lesion volume was poor at all timepoints. Conclusion As CatWalk XT® parameters do not correlate with focal lesion size after CCI, gait assessment using the CatWalk XT® might add valuable information to solitary histologic evaluation of the injury site. While all CatWalk XT® parameters can be used for gait assessments in the first week after CCI, dynamic single paw parameters might be more relevant in the chronic phase after experimental TBI.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Focal lesion size poorly correlates with motor function after experimental traumatic brain injury in mice

et al. 2022

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“…Additionally, these assays are a quantifiable measure of the effectiveness of various therapeutic strategies. However, these motor tests share the limitation of being mainly observer dependent and of detecting only gross deficits in coordination and motor function 12 . For gait analysis, observational scoring as a simple low-technology tool was widely performed 20 years ago.…”

Section: Introductionmentioning

confidence: 99%

“…The system provides a deeper understanding of functional motor impairment by the automatic analysis of several different parameters. This method has previously been used in rodent models of spinal cord injury 20 – 22 , pain 23 – 25 , sciatic nerve injury 26 , 27 , traumatic brain injury 12 , and for the behavioral characterization of rodent models of CNS-based movement disorders 28 – 32 .…”

Section: Introductionmentioning

confidence: 99%

Gait performance of adolescent mice assessed by the CatWalk XT depends on age, strain and sex and correlates with speed and body weight

Pitzer

Kurpiers

Eltokhi

2021

Sci Rep

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The automatization of behavioral tests assessing motor activity in rodent models is important for providing robust and reproducible results and evaluating new therapeutics. The CatWalk system is an observer-independent, automated and computerized technique for the assessment of gait performance in rodents. This method has previously been used in adult rodent models of CNS-based movement disorders such as Parkinson’s and Huntington’s diseases. As motor and gait abnormalities in neuropsychiatric disorders are observed during infancy and adolescence, it became important to validate the CatWalk XT in the gait analysis of adolescent mice and unravel factors that may cause variations in gait performance. Three adolescent wild-type inbred mouse strains, C57BL/6N, DBA/2 and FVB/N, were tested using the CatWalk XT (Version 10.6) for suitable detection settings to characterize several gait parameters at P32 and P42. The same detection settings being suitable for C57BL/6N and DBA/2 mice allowed a direct comparison between the two strains. On the other hand, due to their increased body weight and size, FVB/N mice required different detection settings. The CatWalk XT reliably measured the temporal, spatial, and interlimb coordination parameters in the investigated strains during adolescence. Additionally, significant effects of sex, development, speed and body weight within each strain confirmed the sensitivity of motor and gait functions to these factors. The CatWalk gait analysis of rodents during adolescence, taking the effect of age, strain, sex, speed and body weight into consideration, will decrease intra-laboratory discrepancies and increase the face validity of rodent models of neuropsychiatric disorders.

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“…The mouse was placed on the open end of an enclosed glass platform and walked across the glass floor voluntarily, during which a high-speed camera underneath the device captured images of each paw and transmitted the data to gait analysis software (CatWalk XT, version 10.6; Noldus) [ 46 , 88 ]. In this study, eight available parameters were identified to assess the dynamic behaviors relevant to NP [ 88 , 89 ]: (1) regularity index as the degree of inter-limb coordination as a percentage of complete coordination; (2) stand as the duration of a paw touching the glass plate; (3) body speed is calculated by counting the distance of the mouse's body (paws) from the initial contact with the glass plate to the next contact divided by the time required to move this distance; (4) standing on three as the percentage of time spent walking with three paws; (5) print length as the length of the paw print (horizontal direction); (6) print width as the width of the complete paw print (vertical direction); (7) max contact area as the maximum print area during paw contact; and (8) max contact mean intensity as the mean intensity at maximum paw contact.…”

Section: Methodsmentioning

confidence: 99%

Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission

Zhang

et al. 2022

Redox Biology

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Mitochondria play an essential role in pathophysiology of both inflammatory and neuropathic pain (NP), but the mechanisms are not yet clear. Dynamin-related protein 1 (Drp1) is broadly expressed in the central nervous system and plays a role in the induction of mitochondrial fission process. Spared nerve injury (SNI), due to the dysfunction of the neurons within the spinal dorsal horn (SDH), is the most common NP model. We explored the neuroprotective role of Drp1 within SDH in SNI. SNI mice showed pain behavior and anxiety-like behavior, which was associated with elevation of Drp1, as well as increased density of mitochondria in SDH. Ultrastructural analysis showed SNI induced damaged mitochondria into smaller perimeter and area, tending to be circular. Characteristics of vacuole in the mitochondria further showed SNI induced the increased number of vacuole, widened vac-perimeter and vac-area. Stable overexpression of Drp1 via AAV under the control of the Drp1 promoter by intraspinal injection (Drp1 OE) attenuated abnormal gait and alleviated pain hypersensitivity of SNI mice. Mitochondrial ultrastructure analysis showed that the increased density of mitochondria induced by SNI was recovered by Drp1 OE which, however, did not change mitochondrial morphology and vacuole parameters within SDH. Contrary to Drp1 OE, down-regulation of Drp1 in the SDH by AAV-Drp1 shRNA (Drp1 RNAi) did not alter painful behavior induced by SNI. Ultrastructural analysis showed the treatment by combination of SNI and Drp1 RNAi (SNI + Drp1 RNAi) amplified the damages of mitochondria with the decreased distribution density, increased perimeter and area, as well as larger circularity tending to be more circular. Vacuole data showed SNI + Drp1 RNAi increased vacuole density, perimeter and area within the SDH mitochondria. Our results illustrate that mitochondria within the SDH are sensitive to NP, and targeted mitochondrial Drp1 overexpression attenuates pain hypersensitivity. Drp1 offers a novel therapeutic target for pain treatment.

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The CatWalk XT® is a valid tool for objective assessment of motor function in the acute phase after controlled cortical impact in mice

Cited by 23 publications

References 48 publications

Focal lesion size poorly correlates with motor function after experimental traumatic brain injury in mice

Focal lesion size poorly correlates with motor function after experimental traumatic brain injury in mice

Gait performance of adolescent mice assessed by the CatWalk XT depends on age, strain and sex and correlates with speed and body weight

Targeted up-regulation of Drp1 in dorsal horn attenuates neuropathic pain hypersensitivity by increasing mitochondrial fission

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