Neuropathological mRNA Expression Changes after Single Mild Traumatic Brain Injury in Pigs

Area of Science:

• Neuroscience
• Genomics
• Pathology

Background:

• Traumatic brain injury (TBI), particularly mild TBI (concussion), affects millions globally.
• Clinical studies on cellular changes post-mild TBI are limited due to infrequent mortality and rapid recovery.
• A large gyrencephalic pig model replicates human-like biomechanical loading for concussion research.

Purpose of the Study:

• To investigate transcriptomic changes following a mild, closed-head, rotational acceleration-induced TBI in a large animal model.
• To identify neurodegenerative analytes and gene expression patterns at various time points post-injury.
• To explore potential therapeutic targets for mild TBI.

Main Methods:

• Utilized a pig model subjected to mild TBI via rotational acceleration.
• Collected tissue samples at 3 days post-injury (DPI), 30 DPI, and 1 year post-injury (YPI), comparing to sham controls.
• Performed transcriptomic analysis using Nanostring neuropathology panel on RNA from fixed brain tissue.

Main Results:

• Identified 11 differentially expressed genes at 3 DPI, including SYT1, NF1, and SORL1.
• Observed no differentially expressed genes at 30 DPI or 1 YPI compared to shams.
• Detected significant gene set alterations, including chromatin modification and autophagy at 3 DPI, and cytokines at 30 DPI, with persistent dysregulation up to 1 YPI.

Conclusions:

• Transcriptomic analysis in a clinically relevant large animal model reveals acute molecular changes post-mild TBI.
• Specific gene expression alterations at 3 DPI suggest early cellular responses and potential biomarkers.
• The study identifies potential therapeutic targets and pathways for future investigation in mild TBI recovery.