Repetitive mild closed-head injury induced synapse loss and increased local BOLD-fMRI signal homogeneity

Abstract

AbstractRepeated mild head injuries due to sports, or domestic violence and military service are increasingly linked to debilitating symptoms in the long term. Although symptoms may take decades to manifest, potentially treatable neurobiological alterations must begin shortly after injury. Better means to diagnose and treat traumatic brain injuries, requires an improved understanding of the mechanisms underlying progression and means through which they can be measured. Here, we employ a repetitive mild closed-head injury (rmTBI) and chronic variable stress (CVS) mouse model to investigate emergent structural and functional brain abnormalities. Brain imaging is achieved with [18F]SynVesT-1 positron emission tomography, with the synaptic vesicle glycoprotein 2A ligand marking synapse density and BOLD (blood-oxygen-level-dependent) functional magnetic resonance imaging (fMRI). Animals were scanned six weeks after concluding rmTBI/Stress procedures. Injured mice showed widespreaddecreasesin synaptic density coupled with an increasein local BOLD-fMRI synchrony detected as regional homogeneity. Injury-affected regions withhighersynapse density showed agreater increasein fMRI regional homogeneity. Taken together, these observations may reflect compensatory mechanisms following injury. Multimodal studies are needed to provide deeper insights into these observations.