A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Rattka, Marta; Krstić, Miloš; Asan, Esther; Volkmann, Jens

doi:10.3791/53951

Cited by 7 publications

(11 citation statements)

References 29 publications

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“…Whereas hand use is important to most human activities, rodents also use their hands for building nests, digging, walking, running, climbing, pulling strings, grooming, caring for young, and for feeding-essentially, for much of their behavior. A number of laboratory tests have been developed to assess skilled hand use in rodents, including having an animal reach into a tube or through a window to retrieve a food pellet or having an animal operate a manipulandum or pull on a string to obtain food [3][4][5][6][7][8][9][10][11]. In addition, skilled walking tasks assess rodent fore-and hind limb placement on a narrow beam or while crossing a horizontal ladder with regularly or irregularly spaced rungs [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Data-driven analyses of motor impairments in animal models of neurological disorders

et al. 2019

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Behavior provides important insights into neuronal processes. For example, analysis of reaching movements can give a reliable indication of the degree of impairment in neurological disorders such as stroke, Parkinson disease, or Huntington disease. The analysis of such movement abnormalities is notoriously difficult and requires a trained evaluator. Here, we show that a deep neural network is able to score behavioral impairments with expert accuracy in rodent models of stroke. The same network was also trained to successfully score movements in a variety of other behavioral tasks. The neural network also uncovered novel movement alterations related to stroke, which had higher predictive power of stroke volume than the movement components defined by human experts. Moreover, when the regression network was trained only on categorical information (control = 0; stroke = 1), it generated predictions with intermediate values between 0 and 1 that matched the human expert scores of stroke severity. The network thus offers a new data-driven approach to automatically derive ratings of motor impairments. Altogether, this network can provide a reliable neurological assessment and can assist the design of behavioral indices to diagnose and monitor neurological disorders.

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Section: Introductionmentioning

confidence: 99%

Data-driven analyses of motor impairments in animal models of neurological disorders

et al. 2019

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“…The device is designed to encourage animals to get food through confined spaces (40). The rats are generally food-deprived 3 days before the assessment, and trained for 2-3 weeks before this task (5 days per week, two 15-min trials a day with a 4-5 h duration) (64,81). Normal animals can usually collect pellets quickly (77).…”

Section: Staircase Testmentioning

confidence: 99%

“…The range of normal values is above nine pellets on each side in both mice and rats (64,80). This test has been proven to be sensitive to persistent defects in the detection of ischemic brain injury (40,81). Potential drawbacks of this test are that detailed behavior cannot always be well-quantified (40) and that long-term pre-training is needed (77).…”

Section: Staircase Testmentioning

confidence: 99%

“…Potential drawbacks of this test are that detailed behavior cannot always be well-quantified ( 40 ) and that long-term pre-training is needed ( 77 ). The video of detailed procedures for rats is available in reference ( 82 ).…”

Section: Common Behavioral Assessmentsmentioning

confidence: 99%

“…The video of detailed procedures for mice can be seen in reference ( 92 ). The video of detailed procedures for rats can be seen in reference ( 82 ). The cylinder test is low-costing and easy to perform.…”

Section: Common Behavioral Assessmentsmentioning

confidence: 99%

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Behavioral Assessment of Sensory, Motor, Emotion, and Cognition in Rodent Models of Intracerebral Hemorrhage

et al. 2021

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Intracerebral hemorrhage (ICH) is the second most common type of stroke and has one of the highest fatality rates of any disease. There are many clinical signs and symptoms after ICH due to brain cell injury and network disruption resulted from the rupture of a tiny artery and activation of inflammatory cells, such as motor dysfunction, sensory impairment, cognitive impairment, and emotional disturbance, etc. Thus, researchers have established many tests to evaluate behavioral changes in rodent ICH models, in order to achieve a better understanding and thus improvements in the prognosis for the clinical treatment of stroke. This review summarizes existing protocols that have been applied to assess neurologic function outcomes in the rodent ICH models such as pain, motor, cognition, and emotion tests. Pain tests include mechanical, hot, and cold pain tests; motor tests include the following 12 types: neurologic deficit scale test, staircase test, rotarod test, cylinder test, grid walk test, forelimb placing test, wire hanging test, modified neurologic severity score, beam walking test, horizontal ladder test, and adhesive removal test; learning and memory tests include Morris water maze, Y-maze, and novel object recognition test; emotion tests include elevated plus maze, sucrose preference test, tail suspension test, open field test, and forced swim test. This review discusses these assessments by examining their rationale, setup, duration, baseline, procedures as well as comparing their pros and cons, thus guiding researchers to select the most appropriate behavioral tests for preclinical ICH research.

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Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system

Apetz¹,

Paralikar²,

Neumaier³

et al. 2021

J. Neural Eng.

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Objective. This study aimed at investigating a novel fully implantable deep brain stimulation (DBS) system and its ability to modulate brain metabolism and behavior through subthalamic nucleus (STN) stimulation in a hemiparkinsonian rat model. Approach. Twelve male rats were unilaterally lesioned with 6-hydroxydopamine in the medial forebrain bundle and received a fully implantable DBS system aiming at the ipsilesional STN. Each rat underwent three cylinder tests to analyze front paw use: a PRE test before any surgical intervention, an OFF test after surgery but before stimulation onset and an ON test under DBS. To visualize brain glucose metabolism in the awake animal, two [18F]FDG scans were conducted in the OFF and ON condition. At least 4 weeks after surgery, an [18F]FDOPA scan was used to check for dopaminergic integrity. Main results. In general, STN DBS increased [18F]FDG uptake ipsilesionally and decreased it contralesionally. More specifically, bilateral orbitofrontal cortex, ipsilateral caudate putamen, sensorimotor cortex and nucleus accumbens showed significantly higher tracer uptake in ON compared to OFF condition. Contralateral cingulate and secondary motor cortex, caudate putamen, amygdala, hippocampus, retrosplenial granular cortex, superior colliculus, and parts of the cerebellum exhibited significantly higher [18F]FDG uptake in the OFF condition. On the behavioral level, stimulation was able improve use of the contralesional affected front paw suggesting an effective stimulation produced by the implanted system. Significance. The fully implantable stimulation system developed by us and presented here offers the output of arbitrary user-defined waveforms, patterns and stimulation settings and allows tracer accumulation in freely moving animals. It is therefore a suitable device for implementing behavioral PET studies. It contributes immensely to the possibilities to characterize and unveil the effects and mechanisms of DBS offering valuable clues for future improvements of this therapy.

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A Novel Approach to Assess Motor Outcome of Deep Brain Stimulation Effects in the Hemiparkinsonian Rat: Staircase and Cylinder Test

Cited by 7 publications

References 29 publications

Data-driven analyses of motor impairments in animal models of neurological disorders

Data-driven analyses of motor impairments in animal models of neurological disorders

Behavioral Assessment of Sensory, Motor, Emotion, and Cognition in Rodent Models of Intracerebral Hemorrhage

Towards chronic deep brain stimulation in freely moving hemiparkinsonian rats: applicability and functionality of a fully implantable stimulation system

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