Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy

Abstract

Traumatic brain injury (TBI) presents a widespread health problem in the elderly population. In addition to the acute injury, epidemiological studies have observed an increased probability and earlier onset of dementias in the elderly following TBI. However, the underlying mechanisms of the connection between TBI and Alzheimer’s disease in the aged brain and potential exacerbating factors is still evolving. The aim of this study was to investigate cellular injury-induced processes in the presence of amyloid β (Aβ) pathology. For this purpose, a co-culture system of cortical stem-cell derived astrocytes, neurons and oligodendrocytes were exposed to Aβ42 protofibrils prior to a mechanically induced scratch injury. Cellular responses, including neurodegeneration, glial activation and autophagy was assessed by immunoblotting, immunocytochemistry, ELISA and transmission electron microscopy. Our results demonstrate that the combined burden of Aβ exposure and experimental TBI causes a decline in the number of neurons, the differential expression of the key astrocytic markers glial fibrillary acidic protein and S100 calcium-binding protein beta, mitochondrial alterations and prevents the upregulation of autophagy. Our study provides valuable information about the impact of TBI sustained in the presence of Aβ deposits and helps to advance the understanding of geriatric TBI on the cellular level.

Identifying mild traumatic brain injury using measures of frequency-specified networks

“…Advanced optical imaging techniques, such as widefield calcium imaging in animals, has provided a unique opportunity to study brain function by enabling recording of the neural activity with high temporal and spatial resolutions. Indeed, such a technique has been recently used to study the relationship between the brain function and behavior [15][16][17][18][19], as well as the relationship between the brain function and injury [20][21][22][23][24][25][26]. Brain FC networks have also been investigated using calcium signals [16,22,[27][28][29].…”

Blunt Traumatic Brain Injury and Alzheimer Pathology

“…Some studies suggested that tau phosphorylation induced by severe closed TBI is linked to the cellular prion protein [43]. Several studies found both Aβ and tau accumulation after TBI [44][45][46][47][48][49][50][51], affecting neuronal survival, glial activation, neuroinflammation, and other pathomechanisms, thus indicating overlapping pathways between TBI and AD [1,52], while others suggested vascular disorders as promoting factors [53].…”