Peripheral immune cell dysregulation following diffuse traumatic brain injury in pigs

Area of Science:

• Neuroscience
• Immunology
• Traumatic Brain Injury Research

Background:

• Traumatic brain injury (TBI) is a major global health issue with significant neurological and mortality consequences.
• TBI disrupts the brain-peripheral organ communication, leading to immune dysregulation and increased infection risk.
• The impact of injury severity on the peripheral immune system in diffuse TBI remains poorly understood.

Purpose of the Study:

• To investigate how injury severity affects peripheral blood mononuclear cells (PBMCs) and plasma in a large-animal model of diffuse TBI.
• To characterize temporal changes in PBMC concentration, composition, and function following TBI.
• To explore the potential of peripheral immune cell characterization as a diagnostic tool for TBI.

Main Methods:

• Utilized a large-animal model (pigs) subjected to closed-head, diffuse rotational acceleration TBI.
• Collected peripheral blood samples over time across varying injury severities.
• Analyzed plasma cytokine concentrations and characterized PBMCs, including cell concentrations, composition, and phagocytic activity.

Main Results:

• No significant changes were observed in plasma cytokine concentrations across all injury levels and timepoints.
• Peripheral blood mononuclear cell (PBMC) concentrations and physiology demonstrated injury severity-dependent alterations.
• Significant cellular changes in PBMCs were most prominent within 10 days following high-velocity rotational injuries, including alterations in myeloid and T cell populations and phagocytic clearance.

Conclusions:

• Diffuse TBI in a clinically relevant large-animal model induces detectable peripheral immune system perturbations into the subacute phase.
• PBMC alterations following TBI are injury severity-dependent and occur in a time-sensitive manner.
• Peripheral blood cellular characterization holds promise as a potential diagnostic biomarker for TBI and may guide future immunomodulatory therapeutic strategies.