Linking Cerebral Hemodynamics and Neuroinflammation to Alzheimer's Pathology in Repetitive Mild Traumatic Brain Injury
Abstract
Project Purpose and Goals: Repetitive mild traumatic brain injuries (rmTBI) not only take a toll on a patient's immediate well-being, but are also associated with increased risk of neurodegenerative disease. In the current study, we quantified cerebral blood flow together with immune protein and transcriptional profiling in 3xTg-AD mice to identify the effects of rmTBI and relationships among cerebral blood flow, immune markers, and transcripts (Aim 1). We also modulated p38 MAPK immune signaling to determine its role in regulating brain immunity and pathological markers (Aim 2).Major Findings. The key outcome of this study is the identification of a neuroimmune cascade of mild traumatic brain injury in 3xTg-AD mice, consisting of i) an immediate decrease in neuronal homeostatic gene expression and an elevation of AD-associated genes after a single injury, ii) elevation of a subset of cortical cytokines that co-label with neurons after each successive injury in correlation with phosphorylated tau, and iii) increased expression of non-neuronal genes suggesting glial reactivity within days of repeated injury. We provide resolution of these acute protein and transcriptional changes at a previously uncharacterized minutes-to-days time scale alongside the key experimental variables of sex, brain region, and number of injuries.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2023
- Accession Number
- AD1229834
Entities
People
- Levi B. Wood
Organizations
- Georgia Tech Research Corporation