Automated Gait Analysis to Assess Functional Recovery in Rodents with Peripheral Nerve or Spinal Cord Contusion Injury

Heinzel, Johannes; Swiadek, Nicole Victoria; Ashmwe, Mohamed; Rührnößl, Alexander; Oberhauser, Viola; Kolbenschlag, Jonas; Hercher, David

doi:10.3791/61852

Cited by 9 publications

(5 citation statements)

References 6 publications

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“…It should be noted that while the primary focus of this work has been gait analysis in pre-clinical mouse models of human diseases, extension to rat models is theoretically plausible. For example, comparable effects on stand time and print area following peripheral nerve injury have been previously reported in both mice and rats ( Heinzel et al, 2020b ). In addition, a significant decrease in swing speed, duty cycle, and paw print intensity have been observed in both mouse and rat stroke models ( Encarnacion et al, 2011 ; Hetze et al, 2012 ).…”

Section: Discussionsupporting

confidence: 63%

CatWalk XT gait parameters: a review of reported parameters in pre-clinical studies of multiple central nervous system and peripheral nervous system disease models

Timotius¹,

Roelofs²,

Richmond-Hacham³

et al. 2023

Front. Behav. Neurosci.

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Automated gait assessment tests are used in studies of disorders characterized by gait impairment. CatWalk XT is one of the first commercially available automated systems for analyzing the gait of rodents and is currently the most used system in peer-reviewed publications. This automated gait analysis system can generate a large number of gait parameters. However, this creates a new challenge in selecting relevant parameters that describe the changes within a particular disease model. Here, for the first time, we performed a multi-disorder review on published CatWalk XT data. We identify commonly reported CatWalk XT gait parameters derived from 91 peer-reviewed experimental studies in mice, covering six disorders of the central nervous system (CNS) and peripheral nervous system (PNS). The disorders modeled in mice were traumatic brain injury (TBI), stroke, sciatic nerve injury (SNI), spinal cord injury (SCI), Parkinson’s disease (PD), and ataxia. Our review consisted of parameter selection, clustering, categorization, statistical evaluation, and data visualization. It suggests that certain gait parameters serve as potential indicators of gait dysfunction across multiple disease models, while others are specific to particular models. The findings also suggest that the more site-specific the injury is, the fewer parameters are reported to characterize its gait abnormalities. This study strives to present a clearly organized picture of gait parameters used in each one of the different mouse models, potentially helping novel CatWalk XT users to apply this information to similar or related mouse models they are working on.

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Section: Discussionsupporting

confidence: 63%

CatWalk XT gait parameters: a review of reported parameters in pre-clinical studies of multiple central nervous system and peripheral nervous system disease models

Timotius¹,

Roelofs²,

Richmond-Hacham³

et al. 2023

Front. Behav. Neurosci.

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“…This would require more advanced tools capable of testing the temporospatial alteration of the movements, such as the multifactorial motor behavior assessment system to analyze limb kinematics, kinetics, and multi-directional forces, and electrophysiological metrics to decipher the motor problems in this model [64]. For gait analysis, automatic gait analysis devices such as DigiGait (MouseSpecifics, Inc.) and CatWalk XT (Noldus) can be used [65]. These devices analyze gait in different dimensions and, consequently, subtle motor deficits can be detected and analyzed.…”

Section: Discussionmentioning

confidence: 99%

The Development of Hindlimb Postural Asymmetry Induced by Focal Traumatic Brain Injury Is Not Related to Serotonin 2A/C Receptor Expression in the Spinal Cord

Andersen

Güler

Larsen

et al. 2022

IJMS

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Brain injury and stroke are leading causes of adult disability. Motor deficits are common problems, and their underlying pathological mechanisms remain poorly understood. The serotoninergic system is implicated in both functional recovery from and the occurrence of spasticity after injuries to the central nervous system. This study, which was conducted on rats, investigated the development of limb postural changes and their relationship to the expression of serotonin (5-HT) 2A and 2C receptors in the spinal cord in the 4 weeks after focal traumatic brain injury (TBI) to the right hindlimb sensorimotor cortex. The limb motor deficits were assessed by measuring gait pattern changes during walking and hindlimb postural asymmetry at different time intervals (3–28 days) after surgery. The expressions of the 5-HT2A and 2C receptors in the lumbar spinal cord were investigated using immunohistochemistry. The results showed that all the rats with TBI, independently of the duration of the interval, displayed postural asymmetry with flexion on the contralateral (left) side (>2 mm), while the sham-operated rats showed no apparent postural asymmetry. The TBI rats also had longer stride lengths during walking in both their hindlimbs and their forelimbs compared with the sham rats. For both the TBI and the sham rats, the hind-paw placement angles were larger on the contralateral side in some of the groups. Compared to the sham-operated rats, the 5-HT2A and 2C receptor expression did not significantly change on either side of the lumbar spinal cords of the TBI rats in any of the groups. These results suggest that focal TBI can induce motor deficits lasting a relatively long time, and that these deficits are not related to the expression of the 5-HT2A and 2C receptors in the spinal cord.

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“…Nevertheless, Camsap3-cKO mice did show slightly altered gaits in their paw area at peak stance and maximum dA/dt. Assessment of paw placement during walking is often used to evaluate pain (Griffioen et al, 2015;Deuis et al, 2017), pain-killer medicines (Brings et al, 2021), diseases (Bernardes and Oliveira, 2017), and recovery of injuries including both peripheral and central nerve injury (Neumann et al, 2009;Heinzel et al, 2020). Mice with numbers of disorders decrease their paw area to form "tip-toe walking" patterns (Furusawa et al, 1996;Moskovitz et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Vestibular Hair Cells Require CAMSAP3, a Microtubule Minus-End Regulator, for Formation of Normal Kinocilia

O’Donnell

Zheng²

2022

Front. Cell. Neurosci.

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Kinocilia are exceptionally long primary sensory cilia located on vestibular hair cells, which are essential for transmitting key signals that contribute to mammalian balance and overall vestibular system function. Kinocilia have a “9+2” microtubule (MT) configuration with nine doublet MTs surrounding two central singlet MTs. This is uncommon as most mammalian primary sensory cilia have a “9+0” configuration, in which the central MT pair is absent. It has yet to be determined what the function of the central MT pair is in kinocilia. Calmodulin-regulated spectrin-associated protein 3 (CAMSAP3) regulates the minus end of MTs and is essential for forming the central MT pair in motile cilia, which have the “9+2” configuration. To explore the role of the central MT pair in kinocilia, we created a conditional knockout model (cKO), Camsap3-cKO, which intended to eliminate CAMSAP3 in limited organs including the inner ear, olfactory bulb, and kidneys. Immunofluorescent staining of vestibular organs demonstrated that CAMSAP3 proteins were significantly reduced in Camsap3-cKO mice and that aged Camsap3-cKO mice had significantly shorter kinocilia than their wildtype littermates. Transmission electron microscopy showed that aged Camsap3-cKO mice were in fact missing that the central MT pair in kinocilia more often than their wildtype counterparts. In the examination of behavior, wildtype and Camsap3-cKO mice performed equally well on a swim assessment, right-reflex test, and evaluation of balance on a rotarod. However, Camsap3-cKO mice showed slightly altered gaits including reduced maximal rate of change of paw area and a smaller paw area in contact with the surface. Although Camsap3-cKO mice had no differences in olfaction from their wildtype counterparts, Camsap3-cKO mice did have kidney dysfunction that deteriorated their health. Thus, CAMSAP3 is important for establishing and/or maintaining the normal structure of kinocilia and kidney function but is not essential for normal olfaction. Our data supports our hypothesis that CAMSAP3 is critical for construction of the central MT pair in kinocilia, and that the central MT pair may be important for building long and stable axonemes in these kinocilia. Whether shorter kinocilia might lead to abnormal vestibular function and altered gaits in older Camsap3-cKO mice requires further investigation.

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Automated Gait Analysis to Assess Functional Recovery in Rodents with Peripheral Nerve or Spinal Cord Contusion Injury

Cited by 9 publications

References 6 publications

CatWalk XT gait parameters: a review of reported parameters in pre-clinical studies of multiple central nervous system and peripheral nervous system disease models

CatWalk XT gait parameters: a review of reported parameters in pre-clinical studies of multiple central nervous system and peripheral nervous system disease models

The Development of Hindlimb Postural Asymmetry Induced by Focal Traumatic Brain Injury Is Not Related to Serotonin 2A/C Receptor Expression in the Spinal Cord

Vestibular Hair Cells Require CAMSAP3, a Microtubule Minus-End Regulator, for Formation of Normal Kinocilia

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