The effects of mild closed head injuries on tauopathy and cognitive deficits in rodents: Primary results in wild type and rTg4510 mice, and a systematic review

Bachstetter, Adam D.; Morganti, Josh M.; Bodnar, Colleen N.; Webster, Scott J.; Higgins, Emma K.; Roberts, Kelly N.; Snider, Henry C.; Meier, Shelby E.; Nation, Grant K.; Goulding, Danielle S.; Hamm, Matthew; Powell, David K.; Vandsburger, Moriel; Eldik, Linda J. Van; Abisambra, Jose F.

doi:10.1016/j.expneurol.2020.113180

Cited by 22 publications

(23 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A major finding of our study was that the reduction in the number of trials significantly separates the acquisition curves of CHI and SHAM mice and the sex of the mice had no effect on results. Previously, we demonstrated that mice had memory impairment in a 6-arm RAWM at 2 week post-CHI in a 4-day protocol and 15-trial per day [30] or in 2-day protocol and 15-trial per day [27,36]. In the current study we did not attempt to replicate our prior RAWM protocols for a direct experimental comparison of effect size.…”

Section: Discussionmentioning

confidence: 81%

“…The current study is not the first to use RAWM in rodent models of TBI. In addition to our studies using RAWM in CHI models of TBI [27,28,30,36], the RAWM has also been used in models of TBI caused by a controlled cortical impact (CCI) and fluid percussion injury (FPI) of varying injury severities. For instance, TBI-induced deficits have been reported following a CCI using a two-day RAWM protocol [40,41], and three-day RAWM protocol [42].…”

Section: Discussionmentioning

confidence: 99%

“…In this experiment, we evaluated whether our 7-trial protocol was able to detect memory deficits in a mTBI model. In the past, it has been shown that the same animal model of CHI was memory impaired in a 6-arm RAWM when a 15-trial protocol and 2-day test [27,36] and a 15-trial protocol and 4-day test [30] protocol were used. To compare differences between SHAM and CHI mice, we used the median of errors made during the 4-day test ( Fig 5A).…”

Section: Experiments 3: Chi Impairs Rawm Performance 2-week Post-injurymentioning

confidence: 99%

See 2 more Smart Citations

Optimization and validation of a modified radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

et al. 2020

Self Cite

View full text Add to dashboard Cite

Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues influences learning and memory performance. C57BL/6 mice were tested in an 8-arm RAWM using a four-day protocol. We demonstrated that two days of training, exposing the mice to extra-maze cues and a visible platform, influenced learning and memory performance. Mice that did not receive training performed poorer compared to mice trained. To further validate our RAWM protocol, we used scopolamine. We, also, demonstrated that a single mild closed head injury (CHI) caused deficits in this task at two weeks post-CHI. Our data supported the use of 7 trials per day and a spaced training protocol as key factor to unmask memory impairment following CHI. Here, we provide a detailed standard operating procedure for RAWM test, which can be applied to a variety of mouse models including neurodegenerative diseases and pathology, as well as when pharmacological approaches are used.

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Experiments 3: Chi Impairs Rawm Performance 2-week Post-injurymentioning

confidence: 99%

See 1 more Smart Citation

Optimization and validation of a modified radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…In this experiment, we evaluated whether our 7-trial protocol was able to detect memory deficits in a mTBI model. In the past, it has been shown that the same animal model of CHI was memory impaired in a 6-arm RAWM when a 15-trial protocol and 2-day test [27, 36] and a 15-trial protocol and 4-day test [30] protocol were used. To compare differences between SHAM and CHI mice, we used the median of errors made during the 4-day test (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…A major finding of our study was that the reduction of number of trials significantly separates the acquisition curves of CHI and SHAM mice and the sex had no effect on results. Previously, we demonstrated that CHI mice had memory impairment in a 6-arm RAWM at 2 week post-CHI in a 4-day protocol and 15-trial per day [30] or in 2-day protocol and 15-trial per day [27, 36]. However, due to the knowledge that training schedule and spacing of training sessions can impact learning ability [10–13, 24, 25], we sought to determine if reduction of training increased the learning separation between mice affected by mTBI and controls.…”

Section: Discussionmentioning

confidence: 99%

Validation and standardization of a new radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

Macheda

Roberts

Bachstetter

2020

Preprint

Self Cite

View full text Add to dashboard Cite

31 Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions 32 worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better 33 understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced 34 impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to 35 screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for 36 use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the 37 presence of extra-maze cues influences learning and memory performance. C57BL/6 mice were tested in an 38 8-arm RAWM using a four-day protocol. We demonstrated that two days of training, exposing the mice to 39 extra-maze cues and a visible platform, influenced learning and memory performance. Mice that did not 40 receive training performed poorer compared to mice trained. To further validate our RAWM protocol, we used 41 scopolamine. We, also, demonstrated that a single mild closed head injury (CHI) caused deficits in this task at 42 two weeks post-CHI. Our data supported the use of 7 trials per day and a spaced training protocol as key 43 factor to unmask memory impairment following CHI. Here, we provide a detailed standard operating procedure 44 for RAWM test, which can be applied to a variety of mouse models including neurodegenerative diseases and 45 pathology, as well as when pharmacological approaches are used. 46 47 Keywords: traumatic brain injury, mouse, RAWM, TBI, learning and memory, behavioral testing 48 49 50 51 52 53 54 55 56 3 57 Introduction 58 Traumatic brain injury (TBI) is a major public health problem worldwide and leads to temporary or 59 permanent physical and cognitive impairments. In particular, people with a history of TBI have an increase risk 60 to develop dementia and neurodegenerative disease [1, 2]. 61Mechanisms of selective vulnerability to cognitive deficits following a mild TBI are still not well 62 understood, and the use of animal models accelerate a better understanding of the pathological and behavioral 63 outcome associated with a mild TBI. Novel object recognition (NOR) and Morris water maze (MWM) test are 64 the two most popular assays used to evaluate cognitive function after mild TBI [3]. While the radial arm water 65 maze (RAWM) task is becoming a standard tool to assess memory in rodents, only a few studies have used it 66 as tool to evaluate memory in mice after mild TBI [3], and no study has validated optimal methods for the 67 behavior following a mild TBI. 68In 1984, Buresova et al. described a "radial maze in the water tank", making this the first time that water 69 was used as an aversive stimulus in a radial maze [4]. A significant advantage of RAWM is that food 70 deprivation is not required, and odors that could be used by the animal as cues are eliminated. A few years 71 later, Hyde et al. [5] tested three i...

show abstract

Neuronal tau pathology worsens late-phase white matter degeneration after traumatic brain injury in transgenic mice

Iacono

Perl

et al. 2023

Acta Neuropathol

View full text Add to dashboard Cite

Traumatic brain injury (TBI) causes diffuse axonal injury which can produce chronic white matter pathology and subsequent post-traumatic neurodegeneration with poor patient outcomes. Tau modulates axon cytoskeletal functions and undergoes phosphorylation and mis-localization in neurodegenerative disorders. The effects of tau pathology on neurodegeneration after TBI are unclear. We used mice with neuronal expression of human mutant tau to examine effects of pathological tau on white matter pathology after TBI. Adult male and female hTau.P301S (Tg2541) transgenic and wild-type (Wt) mice received either moderate single TBI (s-TBI) or repetitive mild TBI (r-mTBI; once daily × 5), or sham procedures. Acutely, s-TBI produced more extensive axon damage in the corpus callosum (CC) as compared to r-mTBI. After s-TBI, significant CC thinning was present at 6 weeks and 4 months post-injury in Wt and transgenic mice, with homozygous tau expression producing additional pathology of late demyelination. In contrast, r-mTBI did not produce significant CC thinning except at the chronic time point of 4 months in homozygous mice, which exhibited significant CC atrophy (− 29.7%) with increased microgliosis. Serum neurofilament light quantification detected traumatic axonal injury at 1 day post-TBI in Wt and homozygous mice. At 4 months, high tau and neurofilament in homozygous mice implicated tau in chronic axon pathology. These findings did not have sex differences detected. Conclusions: Neuronal tau pathology differentially exacerbated CC pathology based on injury severity and chronicity. Ongoing CC atrophy from s-TBI became accompanied by late demyelination. Pathological tau significantly worsened CC atrophy during the chronic phase after r-mTBI.

show abstract

The effects of mild closed head injuries on tauopathy and cognitive deficits in rodents: Primary results in wild type and rTg4510 mice, and a systematic review

Cited by 22 publications

References 54 publications

Optimization and validation of a modified radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

Optimization and validation of a modified radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

Validation and standardization of a new radial-arm water maze protocol using a murine model of mild closed head traumatic brain injury

Neuronal tau pathology worsens late-phase white matter degeneration after traumatic brain injury in transgenic mice

Contact Info

Product

Resources

About