Biology subjects

Shad, A.

Publications and source records attributed to Shad, A..

3 recordsLinked to original sources

bioRxiv2024

Chronic Behavioral and Seizure Outcomes following Experimental Traumatic Brain Injury and Comorbid Klebsiella pneumoniae Lung Infection in Mice

Traumatic brain injury (TBI) is a leading cause of long-term disability, and infections such as pneumonia represent a common and serious complication for TBI patients in the acute and subacute post-injury period. While the acute effects of infections have been documented, their long-term consequences on neurological and behavioral recovery as well as the potential precipitation of seizures after TBI remain unclear. This study aimed to investigate the chronic effects of Klebsiella pneumoniae infection following TBI, focusing on post-traumatic seizure development and neurobehavioral changes. Using a mouse model, we assessed the long-term effects of TBI and K. pneumoniae infection both in isolation and in combination. We found that, while infection with K. pneumoniae resulted in loss of body weight and increased mortality compared to vehicle-inoculated mice, there was no additional mortality in TBI animals. Further, although TBI alone induced chronic hyperactivity and reduced anxiety-like behaviors, K. pneumoniae lung infection had no lasting effect on these long-term outcomes. Thirdly, while TBI resulted in both spontaneous and evoked seizures long-term post-injury, early post-injury K. pneumoniae infection did not affect late onset seizure susceptibility. Together with recent findings on acute outcomes in this combined insult model of TBI and K. pneumoniae infection, this study suggests that K. pneumoniae does not significantly alter long-term neurobehavioral outcomes or the development of post-traumatic epilepsy. This research highlights the need to further explore the interplay between additional immune insults such as infection that may influence long-term recovery.

neuroscience↗

bioRxiv2024

A post-injury immune challenge with lipopolysaccharide following adult traumatic brain injury alters neuroinflammation and the gut microbiome acutely, but has little effect on chronic outcomes

Patients with a traumatic brain injury (TBI) are susceptible to hospital-acquired infections, presenting a significant challenge to an already-compromised immune system. The consequences and mechanisms by which this dual insult worsens outcomes are poorly understood. This study aimed to explore how a systemic immune stimulus (lipopolysaccharide, LPS) influences outcomes following experimental TBI in young adult mice. Male and female C57Bl/6J mice underwent controlled cortical impact or sham surgery, followed by 1 mg/kg i.p. LPS or saline-vehicle at 4 days post-TBI, before behavioral assessment and tissue collection at 6 h, 24 h, 7 days or 6 months. LPS induced acute sickness behaviors including weight loss, transient hypoactivity, and increased anxiety-like behavior. Early systemic immune activation by LPS was confirmed by increased spleen weight and serum cytokines. In brain tissue, gene expression analysis revealed a time course of inflammatory immune activation in TBI or LPS-treated mice (e.g., IL-1{beta}, IL-6, CCL2, TNF), which was exacerbated in TBI+LPS mice. This group also presented with fecal microbiome dysbiosis at 24 h post-LPS, with reduced bacterial diversity and changes in the relative abundance of key bacterial genera associated with sub-acute neurobehavioral and immune changes. Chronically, TBI induced hyperactivity and cognitive deficits, brain atrophy, and increased seizure susceptibility, similarly in vehicle and LPS-treated groups. Together, findings suggest that an immune challenge with LPS early after TBI, akin to a hospital-acquired infection, alters the acute neuroinflammatory response to injury, but has no lasting effects. Future studies could consider more clinically-relevant models of infection to build upon these findings.

neuroscience↗

bioRxiv2021

Localized, time-dependent responses of rat cranial bone to repeated mild traumatic brain injuries

While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are unclear. We hypothesized that repeated mTBI (rmTBI) would change the microstructure of cranial bones, without gross skull fractures. To address this, young adult female Piebald Viral Glaxo rats received sham, 1x, 2x or 3x closed-head mTBIs delivered at 24h intervals, using a weight-drop device custom built for reproducible impact. Skull bones were collected at 2 or 10 weeks after the final injury/sham procedure, imaged by micro computed tomography and analyzed at predetermined regions of interest. In the interparietal bone, proximal to the injury site, modest increases in bone thickness was observed at 2 weeks, particularly following 3x mTBI. By 10 weeks, 2x mTBI induced a robust increase in the volume and thickness of the interparietal bone, alongside a corresponding decrease in the volume of marrow cavities in the diploe region. In contrast, neither parietal nor frontal skull samples were affected by rmTBI. Our findings demonstrate time- and location-dependent effects of rmTBI on cranial bone structure, highlighting a need to consider microstructural alterations to cranial bone when assessing the consequences of rmTBI.

neuroscience↗