Motor Effects of Minimal Traumatic Brain Injury in Mice

Namdar, I.; Feldman, Ron J.; Glazer, Sandra; Meningher, Inbar; Shlobin, Nathan A.; Rubovitch, Vardit; Bikovski, Lior; Been, Ella; Pick, Chaim G.

doi:10.1007/s12031-019-01422-9

Cited by 15 publications

(29 citation statements)

References 66 publications

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“…Following TBI, changes to overall activity [ 45 ] and sleep disturbances [ 46 ] are commonly experienced in mice and/or humans. Traditional TBI studies often measure locomotion through assays like open field and activity monitoring to determine whether mice are less active following injury, and because we produced an injury to the visual system, we reasoned that activity monitoring could also be used to determine whether circadian rhythms were disrupted in our mice following TBI with 24/7 recording after injury.…”

Section: Resultsmentioning

confidence: 99%

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Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice

Hetzer

Guilhaume-Corrêa

Day

et al. 2021

Cells

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Traumatic brain injury (TBI) results in a number of impairments, often including visual symptoms. In some cases, visual impairments after head trauma are mediated by traumatic injury to the optic nerve, termed traumatic optic neuropathy (TON), which has few effective options for treatment. Using a murine closed-head weight-drop model of head trauma, we previously reported in adult mice that there is relatively selective injury to the optic tract and thalamic/brainstem projections of the visual system. In the current study, we performed blunt head trauma on adolescent C57BL/6 mice and investigated visual impairment in the primary visual system, now including the retina and using behavioral and histologic methods at new time points. After injury, mice displayed evidence of decreased optomotor responses illustrated by decreased optokinetic nystagmus. There did not appear to be a significant change in circadian locomotor behavior patterns, although there was an overall decrease in locomotor behavior in mice with head injury. There was evidence of axonal degeneration of optic nerve fibers with associated retinal ganglion cell death. There was also evidence of astrogliosis and microgliosis in major central targets of optic nerve projections. Further, there was elevated expression of endoplasmic reticulum (ER) stress markers in retinas of injured mice. Visual impairment, histologic markers of gliosis and neurodegeneration, and elevated ER stress marker expression persisted for at least 30 days after injury. The current results extend our previous findings in adult mice into adolescent mice, provide direct evidence of retinal ganglion cell injury after head trauma and suggest that axonal degeneration is associated with elevated ER stress in this model of TON.

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Section: Resultsmentioning

confidence: 99%

“…Following TBI, changes to overall activity [45] and sleep disturbances [46] are commonly experienced in mice and/or humans. Traditional TBI studies often measure loco-…”

Section: Activity But Not Circadian Rhythm Is Affected In This Model Of Traumatic Optic Neuropathymentioning

confidence: 99%

Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice

Hetzer

Guilhaume-Corrêa

Day

et al. 2021

Cells

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“…Our previous study reported no significant motor deficits following a single injury 76 . Even in more mild injuries, motor dysfunction is sometimes detected [77][78][79][80][81][82][83] .…”

Section: Discussionmentioning

confidence: 99%

Repeated mild traumatic brain injuries impair visual discrimination learning in adolescent mice

Pinkowski

Guerin

Zhang

et al. 2020

Neurobiology of Learning and Memory

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“…Longitudinal phenotyping can investigate behavioral changes in a circadian-dependent manner. Namdar et al (2020) showed that mTBI affects mice activity. They measured daily activity by means of the home-cage running wheel, and showed that activity was lower during the active time period (i.e., during the dark cycle) and higher during the resting time period (i.e., during the light cycle) compared with control subjects.…”

Section: Prolonged Observation Of Behaviormentioning

confidence: 99%

Measuring Behavior in the Home Cage: Study Design, Applications, Challenges, and Perspectives

Grieco

Bernstein

Biemans

et al. 2021

Front. Behav. Neurosci.

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The reproducibility crisis (or replication crisis) in biomedical research is a particularly existential and under-addressed issue in the field of behavioral neuroscience, where, in spite of efforts to standardize testing and assay protocols, several known and unknown sources of confounding environmental factors add to variance. Human interference is a major contributor to variability both within and across laboratories, as well as novelty-induced anxiety. Attempts to reduce human interference and to measure more "natural" behaviors in subjects has led to the development of automated home-cage monitoring systems. These systems enable prolonged and longitudinal recordings, and provide large continuous measures of spontaneous behavior that can be analyzed across multiple time scales. In this review, a diverse team of neuroscientists and product developers share their experiences using such an automated monitoring system that combines Noldus PhenoTyper® home-cages and the video-based tracking software, EthoVision® XT, to extract digital biomarkers of motor, emotional, social and cognitive behavior. After presenting our working definition of a “home-cage”, we compare home-cage testing with more conventional out-of-cage tests (e.g., the open field) and outline the various advantages of the former, including opportunities for within-subject analyses and assessments of circadian and ultradian activity. Next, we address technical issues pertaining to the acquisition of behavioral data, such as the fine-tuning of the tracking software and the potential for integration with biotelemetry and optogenetics. Finally, we provide guidance on which behavioral measures to emphasize, how to filter, segment, and analyze behavior, and how to use analysis scripts. We summarize how the PhenoTyper has applications to study neuropharmacology as well as animal models of neurodegenerative and neuropsychiatric illness. Looking forward, we examine current challenges and the impact of new developments. Examples include the automated recognition of specific behaviors, unambiguous tracking of individuals in a social context, the development of more animal-centered measures of behavior and ways of dealing with large datasets. Together, we advocate that by embracing standardized home-cage monitoring platforms like the PhenoTyper, we are poised to directly assess issues pertaining to reproducibility, and more importantly, measure features of rodent behavior under more ethologically relevant scenarios.

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Motor Effects of Minimal Traumatic Brain Injury in Mice

Cited by 15 publications

References 66 publications

Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice

Traumatic Optic Neuropathy Is Associated with Visual Impairment, Neurodegeneration, and Endoplasmic Reticulum Stress in Adolescent Mice

Repeated mild traumatic brain injuries impair visual discrimination learning in adolescent mice

Measuring Behavior in the Home Cage: Study Design, Applications, Challenges, and Perspectives

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