Age-Associated T-Cell Infiltrates Cause Differential Long-Term Neuropathology and Functional Outcomes After Traumatic Brain Injury in Mice

Project: Research project

Project Details

Description

Traumatic brain injury (TBI) afflicts about three million Americans every year. The highest incidence of TBI occurs in adults aged 75 and older who have higher mortality and worse long-term functional outcomes than younger adults. This age-associated outcome difference has also been reported in various animal studies. Yet, the molecular and cellular mechanisms have only been partially elucidated, and age-specific TBI treatments are notably lacking. Preliminary single-cell RNA sequencing (scRNA-seq) data revealed that aged mice post-TBI demonstrated greater increased infiltrating T-cells than young-adult mice. Of note, these T-cell infiltrates upregulate genes involved in pathways such as tau protein binding, macromolecule synthesis, and negative regulation of neuron death. Hence, I hypothesized that this T-cell infiltration contributes to increased vulnerability of the aged brain to TBI. The three- to six-month period of the scholarship, I will validate the scRNA-seq findings via phenotyping T- cell infiltrates and their subtypes in the aged brains post-TBI. I will then examine the accumulation of T-cell infiltrates in the aged brain after TBI by utilizing anti-CD49d antibodies. Anti-CD49d is against a key adhesion molecule integrin alpha 4 of leukocytes, thus reducing the infiltration of circulating T cells. Subsequently, I will perform an in vitro proliferation assay to further interrogate if microglia from aged brains are responsible for the CNS T- cell accumulation.
StatusFinished
Effective start/end date9/8/2212/15/22

Funding

  • American Federation for Aging Research (Schwulst AGMT 08/18/22)

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