Biomarkers and Treatment of Hypobaria-Exacerbated Traumatic Brain Injury (TBI)
Abstract
Our studies have examined the molecular and cellular pathways activated following traumatic brain injury plus hypobaria exposure and their contribution to neuroinflammation leading to neuronal loss and neurological deficits. We focused on key changes in extracellular vesicles, transcriptional activation of microRNA pathways and induction of pro-inflammatory genes. We also studied the effects of cell cycle inhibition using cyclin-dependent kinase (CDK) inhibitors on neuroinflammation, neuronal loss and neurological deficits after experimental traumatic brain injury+hypobaria. Our data suggest that central and systemic (plasma) levels of key pro-inflammatory microRNAs are upregulated afterTBI+hypobaria. Microparticles are also elevated in plasma after injury. Our results also suggest that TBI+hypobaria increases key pro-inflammatory genes in the cortex and hippocampus. In order to greatly increase our ability to quantitatively detect the microRNAs that play key roles in neuroinflammation responses we used the Nanostring approach, a state-of-the-art RNA analysis method. Our data have identified many microRNAs whose expression levels are modulated following TBI+hypobaria, both in the brain and plasma. These novel microRNAs should be the focus of future studies. Our studies have also shown that administration of pharmacological inhibitors of CDKs attenuate neuroinflammation, neuronal loss and cognitive deficits after TBI+hypobaria suggesting that such drugs may serve to protect TBI patientsrequiring aeromedical evacuation
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 04, 2020
- Accession Number
- AD1163242
Entities
People
- Alan I. Faden
Organizations
- University of Maryland, Baltimore