Cell type-specific vulnerability to traumatic brain injury

Traumatic brain injury (TBI) is best characterized as brain dysfunction caused by an outside force, usually a violent blow to the head, often occurring as a result of a severe sports injury or car accident. It is a major global health concern, affecting 69 million people worldwide per year, and is one of the most common causes of disability and death in adults. Nearly 50% of TBI patients experience long term cognitive impairment, linked to hippocampal neuronal damage and death. At the same time a deregulation of the hippocampal neurogenic processes is observed which impedes possible functional recovery of the brain. In particular, immunohistochemistry in mouse hippocampus has shown that cortical TBI affects neural stem and progenitor cells (NSPCs) residing in sub-granular zone of dendrite gyrus. Moreover, severe changes in the states of astrocytes, cells regulating axonal growth and synaptogenesis, has been observed throughout hippocampus. Here, in a collaborative project between VIB-KU Leuven, University of Amsterdam and the Bioinformatics CRO, we explore the cellular response in hippocampus following cortical TBI, exploiting cutting edge single cell RNA sequencing (10X Genomics) and highly multiplexed in situ hybridization (Resolve Biosciences) technologies. We systematically assess the sensitivity of NSPCs, immature astrocytes and immature neurons located in the sub-granular layer of dentate gyrus to TBI-induced pathology at the molecular level. We further characterize molecular changes within the hippocampus and the surrounding tissue, providing a spatial map of gene expression changes with single cell resolution.

Learning Objectives:

1. Single cell and spatial transcriptomics to investigate cell type heterogeneity at the highest resolution.

2. The impact of cortical traumatic brain injury on hippocampus and the surrounding tissue.

3. Effects of traumatic brain injury on neural stem and progenitor cells.