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

Pinkowski, Natalie J.; Guerin, Juliana; Zhang, Haikun; Carpentier, Sydney; McCurdy, Kathryn E.; Pacheco, Johann M.; Mehos, Carissa J.; Brigman, Jonathan L.; Morton, Russell A.

doi:10.1016/j.nlm.2020.107315

Cited by 8 publications

(3 citation statements)

References 99 publications

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“…The OFT results support a previous report that repeated CCI‐induced mTBI did not reduce overall locomotor activity, but increase anxiety in C57BL/6J mice during OFT (Broussard et al, 2018). For the general effects of rmTBI on locomotion, our results agree with two recent rmTBI studies in mice (Pinkowski et al, 2020) and in rats (Feng et al, 2021). In the study of Pinkowski et al, four CHIs (24‐h intervals) were applied over the cingulate gyrus, the mildly injured mice did not show gross motor dysfunction.…”

Section: Discussionsupporting

confidence: 92%

“…In the study of Pinkowski et al, four CHIs (24‐h intervals) were applied over the cingulate gyrus, the mildly injured mice did not show gross motor dysfunction. However, the distance mice traveled in central zones and the total distance traveled in OFT was either slightly reduced or increased, respectively (Pinkowski et al, 2020), at 5 DPI. While in the study of Feng et al, four impacts were delivered with 1‐min intervals on the first day and repeated 48 h later around bregma region; rmTBI rats did not show general locomotor deficits as determined by the total distance traveled and average move velocity.…”

Section: Discussionmentioning

confidence: 99%

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Modified mouse model of repeated mild traumatic brain injury through a thinned‐skull window and fluid percussion

Liu

Fan

Wang

et al. 2023

J of Neuroscience Research

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Mild traumatic brain injury (mTBI) is a clinically highly heterogeneous neurological disorder, none of the existing animal models can replicate the entire sequelae. This study aimed to develop a modified closed head injury (CHI) model of repeated mTBI (rmTBI) for investigating Ca2+ fluctuations of the affected neural network, the alternations of electrophysiology, and behavioral dysfunctions. The transcranial Ca2+ study protocol includes AAV‐GCaMP6s infection in the right motor cortex, thinned‐skull preparation, and two‐photon laser scanning microscopy (TPLSM) imaging. The CHI rmTBI model is fabricated using the thinned‐skull site and applying 2.0 atm fluid percussion with 48‐h interval. The neurological dysfunction, minor motor performance, evident mood, spatial working, and reference deficits we found in this study mimic the clinically relevant syndromes after mTBI. Besides, our study revealed that there was a trend of transition from Ca2+ singlepeak to multipeak and plateau, and the total Ca2+ activities of multipeaks and plateaus (p < .001 vs. pre‐rmTBI value) were significantly increased in ipsilateral layer 2/3 motor neurons after rm TBI. In parallel, there is a low‐frequency power shift from delta to theta band (p < .01 vs. control) in the ipsilateral layer 2/3 of motor cortex of the rmTBI mice, and the overall firing rates significantly increased (p < .01 vs. control). Moreover, rmTBI causes slight cortical and hippocampal neuron damage and possibly induces neurogenesis in the dentate gyrus (DG). The alternations of Ca2+ and electrophysiological characteristics in layer 2/3 neuronal network, histopathological changes, and possible neurogenesis may play concertedly and partially contribute to the functional outcome post‐rmTBI.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Modified mouse model of repeated mild traumatic brain injury through a thinned‐skull window and fluid percussion

Liu

Fan

Wang

et al. 2023

J of Neuroscience Research

View full text Add to dashboard Cite

show abstract

“…Morriss et al 2021 demonstrated that rmTBI, albeit closed head injury in mice, resulted in impaired visual acuity and reduced optic nerve diameter and concluded that visual dysfunction was the main determinant of poor MWM performance [ 17 ]. In another mouse model of closed head rmTBI, Pinkowski et al 2020 reported impairment of visual discrimination learning [ 18 ]. Therefore, the significantly higher latency to the platform observed specifically when starting the test from the NE zone could be vision-related, in addition to an impairment in spatial memory and learning.…”

Section: Discussionmentioning

confidence: 99%

Effects of repetitive mild traumatic brain injury on weight gain and chronic behavioral outcomes in male rats

Graham,

Juzang,

White

2023

PLoS ONE

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To assess the long-term behavioral effects of repetitive mild traumatic brain injury (rmTBI), we employed a preclinical model of rmTBI and performed a battery of behavioral tests starting 14 weeks post-injury. Male Sprague-Dawley rats received four unilateral mild (6 m/s; 0.5 mm depth) controlled cortical impacts (CCI), centered 4 mm posterior and 3–4 mm lateral to the bregma, administered at five-day intervals. The animals’ weights were monitored throughout the study. We tested the rats for anxiety-like (elevated plus maze, open field test), depression-like (forced swim test), locomotor (rotarod, open field test), and spatial learning and memory (Morris water maze (MWM)) behavioral deficits. Overall, a mild behavioral phenotype was observed. Significant deficits were observed with the MWM, indicating that our injury model disrupts spatial learning and memory. An interesting aspect of these data is a directional/visual component to the spatial learning and memory deficits dependent on the zone in which the trial began. With the injury being unilateral, there may be an imbalance in visual acuity that contributes to the observed deficits. Analysis of weight gain data demonstrated that rmTBI reduces weight during the period while injuries are occurring. This may represent another measure that can be tracked to determine injury severity and recovery. RNA-seq analysis demonstrated that gene expression at the chronic endpoint could distinguish between the experimental groups even with a mild behavioral phenotype. Future studies would include a more severe injury paradigm to promote longer-lasting behavior changes.

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Psychosis superspectrum II: neurobiology, treatment, and implications

Kotov,

Carpenter,

Cicero

et al. 2024

Mol Psychiatry

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

Cited by 8 publications

References 99 publications

Modified mouse model of repeated mild traumatic brain injury through a thinned‐skull window and fluid percussion

Modified mouse model of repeated mild traumatic brain injury through a thinned‐skull window and fluid percussion

Effects of repetitive mild traumatic brain injury on weight gain and chronic behavioral outcomes in male rats

Psychosis superspectrum II: neurobiology, treatment, and implications

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