Project description:The goal of this study is to use bulk RNA-sequencing of to observe the effects of High Frequency Head Impacts contibuting to cognitive dysfunction in mice. Our results show HF-HI can alter brain function through synaptic adaptation. HF-HI mice develop chronic cognitive impairments in the absence of traditional brain trauma pathology, and transcriptomic profiling reveals that synapses are a primary target of this effect.
Project description:Vascular disruption has been implicated in COVID-19 pathogenesis, and may predispose to the neurological sequelae associated with the condition (known as Long COVID), yet it remains unclear how blood-brain barrier (BBB) function is affected in these conditions. Here, we show that BBB disruption is evident during acute infection and in Long COVID patients with cognitive impairment, commonly referred to as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), we show BBB disruption correlated with brain volume changes. Transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) revealed dysregulation of the coagulation system and a dampened adaptive immune response in individuals with brain fog. Accordingly, PBMCs showed increased adhesion to human brain endothelial cells in vitro, while exposure of endothelial cells to serum from Long COVID patients induced expression of inflammatory markers. Together, our data suggest that sustained systemic inflammation and persistent localised BBB dysfunction is a key feature of Long COVID-associated brain fog.