Biology subjects

Cheng, W. H.

Publications and source records attributed to Cheng, W. H..

4 recordsLinked to original sources

bioRxiv2026

Repeated mild traumatic brain injury does not affect sleep or epileptiform activity one-month post-injury in a knock-in mouse model of Alzheimer's disease

Traumatic brain injuries (TBIs) are associated with increased risk of neurodegenerative disease, including Alzheimers disease (AD); however, the mechanisms by which TBI promotes AD pathogenesis remain poorly understood. It also remains unclear whether post-TBI sequelae, including sleep disturbances and seizures, play a role in driving disease progression. To investigate these relationships, we employed a translational approach using the Closed-Head Injury Model of Engineered Rotational Acceleration (CHIMERA) of repeated mild TBI (rmTBI) and an AD knock-in mouse model to assess sleep, power spectral density, epileptiform activity, and A{beta} pathology one month post-injury. RmTBI caused elevated neurofilament-light and glial fibrillary acidic protein, markers of neuronal damage. Sex differences were observed in acute injury outcomes, sleep measures, and A{beta} plaque size. Specifically, females exhibited longer recovery post-injury, higher mortality, decreased non-rapid eye movement sleep duration, and larger average plaque size than males at equivalent impact energy. These findings highlight the importance of including both sexes when establishing injury severity thresholds. Future studies should incorporate validated TBI biomarkers of neural injury to define equivalent injury parameters across sexes and examine the chronic effects of rmTBI on sleep, epileptiform activity and AD pathology.

neuroscience↗

bioRxiv2025

Repetitive mild traumatic brain injury causes neuronal damage in the APP/PS1 mouse model of Alzheimer's disease without an enduring impact on amyloid pathology, sleep, or epileptiform activity

Traumatic Brain Injury (TBI) is a known risk factor for Alzheimers disease and related neurodegenerative diseases. Sleep disturbances and epileptiform abnormalities can appear after TBI and may contribute to the development of neuropathology. In this study, we characterized sleep, epileptiform activity, and neuropathology after repetitive mild traumatic brain injury (rmTBI) in a mouse model of Alzheimers disease. We used the Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) to deliver rmTBI or sham (control) treatment to 6-month-old APP/PS1 mice (N=19). One month post-injury, we implanted electroencephalogram (EEG) and electromyographic (EMG) electrodes, recorded for 72 hours, and then collected brain tissue and blood plasma. Our assessment of sleep architecture showed that time spent in vigilance state was not affected by the rmTBI one month post-injury; however, power spectra analysis showed a shift towards higher frequencies in the rmTBI group during non-rapid eye movement (NREM) sleep. Epileptiform activity did not differ between sham and rmTBI. Compared to sham controls, the rmTBI group showed higher neurofilament light (NF-L), but not glial-fibrillary acidic protein (GFAP) in blood plasma and no change in A{beta} pathology. These results indicate sustained neurological injury in the APP/PS1 mice one month after rmTBI without affecting amyloid deposition in the brain. Our study suggests that rmTBI can induce neural injury without causing enduring sleep disruption, seizures, and exacerbation of amyloidosis in the APP/PS1 mouse model.

neuroscience↗

bioRxiv2023

Leveraging the power of 3D brain-wide imaging and mapping tools for brain injury research in murine models

Despite the fundamental importance of understanding impaired brain activity exhibited in post-traumatic epilepsy and other neurological impairments associated with traumatic brain injury (TBI), knowledge of how brain injury affects neuronal activity remains remarkably incomplete. We describe a whole-brain imaging and analysis approach to identify alterations in neuronal activity after TBI as a complementary method to conventional two-dimensional (2D) histological approaches. Here we report an easy-to-follow experimental pipeline to quantify changes in the whole mouse brain using tissue clearing, light sheet microscopy (LSM) and an optimised open-access atlas registration workflow. We validated the outcome of the pipeline using high throughput image analysis software and a secondary atlas registration method. Using the CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration) TBI model, TRAP2 mice were subjected to repeated mild TBI or sham treatment followed by tamoxifen injection to lock c-Fos activity after TBI. Brains were SHIELD fixed and passively cleared for imaging of c-Fos+ cells throughout the rostro-caudal axis of the brain using a light sheet microscope equipped with a specialized whole-brain imaging chamber. Volumetric images were stitched and 3D rendered using Arivis Vision4D image analysis software. For quantitative analysis, 2D image stacks were exported to segment c-Fos+ cells and register them to the Allen Mouse Brain Atlas using the BrainQuant3D python package. As a result, c-Fos+ cell counts were estimated throughout the brain and heatmaps were generated. We identified a brain-wide reduction in c-Fos cell density in the TBI group compared to sham controls, indicative of TBI-induced changes in whole brain neuronal activity. Further studies using multi-dimensional imaging coupled with analysis tools will deepen our understanding of post-TBI brain-wide dynamics.

neuroscience↗

bioRxiv2022

Altered tau in rTg4510 mice after a single interfaced CHIMERA traumatic brain injury

Traumatic brain injury (TBI) in an established risk factor for neurodegenerative disease. In this report, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to study the effects of a single moderate-severe TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice were impacted at 4.0J at 4-mo of age using interfaced CHIMERA and compared to sham controls. Immediately after injury, moderate-severe TBI induced significant mortality (7/15; 47%), and a prolonged duration of loss of righting reflex. At 2-mo post-injury, surviving mice displayed significant histological evidence of microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting showed that TBI mice had a reduced p-GSK-3{beta} (S9):GSK-3{beta} ratio, suggesting greater tau kinase activity. However, tauopathy in surviving TBI mice showed a divergent response, with 3/8 mice having a very low level of tau protein in brain lysates (i.e. lower than sham), and were thus analyzed separately from the other 5/8 TBI mice that maintained the expected level of total tau. Compared to sham controls, TBI mice with normal tau levels had increased p-tau (PHF1 and AT8), increased autophagolysosome accumulation (p62 and Cathepsin D) and decreased hippocampal size. These findings were not observed in TBI mice with low total tau levels. These observations suggest that TBI leads to chronic white matter injury and altered GSK-3{beta} activity. However, post-injury tauopathy and autophagolysosome accumulation diverged in surviving mice through mechanisms that remain to be defined.

neuroscience↗