Peripheral microRNA alteration and pathway signaling after mild traumatic brain injur

Traumatic brain injury (TBI) is a major health concern in the current population. Animal models are increasingly important for identifying early neurobehavioural changes associated with mild to severe as well as repetitive brain injuries. In this study, we analysed behavioural changes in a mouse model of repetitive mild TBI using unbiased quantification metrics. Our approach enabled automated markerless pose estimation of thigmotaxis together with spatial working memory and locomotor activity assessments specifically during the scarcely-studied subacute phase after brain injury. We found that animals exposed to repetitive mild head impacts developed anxiety-like behaviour, manifested by avoidance of the central zone and increased thigmotaxis in the open field test, while maintaining total distance travelled compared to the control group. However, analysis of exploratory behaviour and spatial working memory in the Y-maze, along with assessment of sensorimotor coordination and balance using rotarod tests, revealed no significant difference between the TBI and control groups. These findings suggest that repetitive mTBI is associated with selective anxiety-like behaviour during the subacute phase after brain injury, without detectable motor or cognitive deficits, reflecting the early affective symptomatology frequently reported in clinical populations with mTBI.

Rickettsial infections of the central nervous system (CNS) are manifested by severe neurological symptoms and represent a serious life-threatening condition. Despite the considerable health danger, only a few studies have been conducted focusing on the pathogenesis induced by Rickettsia sp. in CNS. To investigate the signaling pathways associated with the neurotoxic effects of rickettsiae, we employed an experimental model of cerebrocortical neurons combined with molecular profiling and comprehensive bioinformatic analysis. The cytopathic effect induced by Rickettsia akari and Rickettsia slovaca was demonstrated by decreased neuronal viability, structural changes in cell morphology, and extensive fragmentation of neurites in vitro. Targeted profiling revealed the deregulation of genes involved in the neuroinflammatory and neurotoxic cell response pathways. Although quantitative analysis showed differences in gene expression response, functional annotation revealed that the biological processes are largely shared between both Rickettsia species. The identified enriched pathways are associated with cytokine signaling, chemotaxis of immune cells, responses to infectious agents, interactions between neurons, endothelial and glial cells, and regulation of neuronal apoptotic processes. The findings of our study provide new insight into the etiopathogenesis of CNS infection and further expand the understanding of molecular signaling associated with neuroinvasive Rickettsia species.