Gait analysis as a method for assessing neurological outcome in a mouse model of stroke

Hetze, Susann; Römer, Christine; Teufelhart, Carena; Meisel, Andreas; Engel, Odilo

doi:10.1016/j.jneumeth.2012.02.001

Cited by 67 publications

(75 citation statements)

References 32 publications

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“…Additionally to applying modified EAE score, gait parameters were assessed using the semiautomated CatWalk gait analysis system. Previously, we have identified sensitive gait parameters typically affected by stroke in male C57BL/6J mice (Hetze et al, 2012). Here, stroke mice from vehicle and SNS/HPA block groups displayed typical alterations in spatial and kinetic characteristics of gait without significant differences between the groups (Table 1).…”

Section: Blocking Sids Did Not Augment Eae-like Symptoms and Locomotomentioning

confidence: 73%

“…Gait impairments after stroke were assessed using CatWalk (Noldus Information Technology) automated computerassisted method as described in detail previously (Hetze et al, 2012). Before the acquisition of baseline values, mice were trained on the CatWalk system in three sessions (three runs each) on 3 consecutive days.…”

Section: Methodsmentioning

confidence: 99%

“…Poststroke acquisitions were performed 10 and 30 d after MCAo. Stroke-sensitive individual paw and gait parameters were selected based on a previously published model (Hetze et al, 2012). Swing speed was normalized to overcome bias from individual run speed.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Blocking Stroke-Induced Immunodeficiency Increases CNS Antigen-Specific Autoreactivity But Does Not Worsen Functional Outcome after Experimental Stroke

Römer¹,

Engel²,

Winek³

et al. 2015

J. Neurosci.

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Stroke-induced immunodepression (SIDS) is an essential cause of poststroke infections. Pharmacological inhibition of SIDS appearspromising in preventing life-threatening infections in stroke patients. However, SIDS might represent an adaptive mechanism preventing autoreactive immune responses after stroke. To address this, we used myelin oligodendrocyte glycoprotein (MOG) T-cell receptor transgenic (2D2) mice where Ͼ80% of peripheral CD4 ϩ T cells express a functional receptor for MOG. We investigated in a murine model of middle cerebral artery occlusion the effect of blocking SIDS by inhibiting body's main stress axes, the sympathetic nervous system (SNS) with propranolol and the hypothalamic-pituitary-adrenal axis (HPA) with mifepristone. Blockade of both stress axes robustly reduced infarct volumes, decreased infection rate, and increased long-term survival of 2D2 and C57BL/6J wild-type mice. Despite these protective effects, blockade of SIDS increased CNS antigen-specific Type1 T helper cell (Th1) responses in the brains of 2D2 mice 14 d after middle cerebral artery occlusion. One month after experimental stroke, 2D2 mice developed signs of polyradiculitis, which were diminished by SIDS blockade. Adoptive transfer of CD4 ϩ T cells, isolated from 2D2 mice, into lymphocyte-deficient Rag-1KO mice did not reveal differences between SIDS blockade and vehicle treatment in functional long-term outcome after stroke. In conclusion, inhibiting SIDS by pharmacological blockade of body's stress axes increases autoreactive CNS antigen-specific T-cell responses in the brain but does not worsen functional long-term outcome after experimental stroke, even in a mouse model where CNS antigen-specific autoreactive T-cell responses are boosted.

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Section: Blocking Sids Did Not Augment Eae-like Symptoms and Locomotomentioning

confidence: 73%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Blocking Stroke-Induced Immunodeficiency Increases CNS Antigen-Specific Autoreactivity But Does Not Worsen Functional Outcome after Experimental Stroke

Römer¹,

Engel²,

Winek³

et al. 2015

J. Neurosci.

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show abstract

“…The required number of animals per group was calculated with respect to functional outcome in gait analysis (primary endpoint), and 50% improvement in outcome parameters was considered as a relevant effect. 25 Four gait parameters were included as independent measures in the power calculation, and calculations were performed using statistical tables and self-written macros in Microsoft Excel. For power calculation, we have chosen a power of 80%.…”

Section: Discussionmentioning

confidence: 99%

“…Neurologic outcome was determined by assessing characteristic strokeinduced changes in gait parameters as described elsewhere 25 using an automated computer-assisted method (CatWalk, Noldus Information Technology, Wageningen, the Netherlands) according to manufacturer instructions and published procedures. In brief, the system consists of an elevated 1.3-m-long glass plate illuminated with fluorescent light.…”

Section: Neurologic Outcome Measurement With Gait Analysismentioning

confidence: 99%

Superiority of Preventive Antibiotic Treatment Compared with Standard Treatment of Poststroke Pneumonia in Experimental Stroke: A Bed to Bench Approach

Hetze

Engel

Römer

et al. 2013

J Cereb Blood Flow Metab

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Stroke patients are prone to life-threatening bacterial pneumonia. Previous experimental stroke studies have demonstrated that preventive antibiotic treatment (PAT) improves outcome compared with placebo treatment, which however does not model the clinical setting properly. Here we investigate whether PAT is superior to the current clinical 'gold standard' for treating poststroke infections. Therefore, we modeled stroke care according to the current stroke guidelines recommending early antibiotic treatment after diagnosing infections. To reliably diagnose pneumonia in living mice, we established a general health score and a magnetic resonance imaging protocol for radiologic confirmation. Compared with standard treatment after diagnosis by these methods, PAT not only abolished pneumonia successfully but also improved general medical outcome. Both, preventive and standard antibiotic treatment using enrofloxacin improved survival in a similar way compared with placebo treatment. However, in contrast to standard treatment, only PAT improved functional outcome assessed by gait analysis. In conclusion, standard and preventive treatment approach reduced poststroke mortality, however at the cost of a worse neurologic outcome compared with preventive approach. These data support the concept of PAT for treating patients at risk for poststroke infections and warrant phase III trials to prove this concept in clinical setting.

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The Need for Speed in Rodent Locomotion Analyses

Batka

Brown

McMillan

et al. 2014

The Anatomical Record

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Locomotion analysis is now widely used across many animal species to understand the motor defects in disease, functional recovery following neural injury, and the effectiveness of various treatments. More recently, rodent locomotion analysis has become an increasingly popular method in a diverse range of research. Speed is an inseparable aspect of locomotion that is still not fully understood, and its effects are often not properly incorporated while analyzing data. In this hybrid manuscript, we accomplish three things: (1) review the interaction between speed and locomotion variables in rodent studies, (2) comprehensively analyze the relationship between speed and 162 locomotion variables in a group of 16 wild-type mice using the CatWalk gait analysis system, and (3) develop and test a statistical method in which locomotion variables are analyzed and reported in the context of speed. Notable results include the following: (1) over 90% of variables, reported by CatWalk, were dependent on speed with an average R2 value of 0.624, (2) most variables were related to speed in a nonlinear manner, (3) current methods of controlling for speed are insufficient, and (4) the linear mixed model is an appropriate and effective statistical method for locomotion analyses that is inclusive of speed-dependent relationships. Given the pervasive dependency of locomotion variables on speed, we maintain that valid conclusions from locomotion analyses cannot be made unless they are analyzed and reported within the context of speed.

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Gait analysis as a method for assessing neurological outcome in a mouse model of stroke

Cited by 67 publications

References 32 publications

Blocking Stroke-Induced Immunodeficiency Increases CNS Antigen-Specific Autoreactivity But Does Not Worsen Functional Outcome after Experimental Stroke

Blocking Stroke-Induced Immunodeficiency Increases CNS Antigen-Specific Autoreactivity But Does Not Worsen Functional Outcome after Experimental Stroke

Superiority of Preventive Antibiotic Treatment Compared with Standard Treatment of Poststroke Pneumonia in Experimental Stroke: A Bed to Bench Approach

The Need for Speed in Rodent Locomotion Analyses

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