Effect of the nonselective beta blocker propranolol on mice splenic and blood monocytes populations post repeated mild traumatic brain injury
Smith, Jared, Indiana University School of Medicine; Jared Smith, Medical Scientist Training Program, Indiana University School of Medicine; Tyler Nguyen, Department of Anesthesia, Indiana University School of Medicine; Brittany Davis, Department of Anesthesia, Indiana University School of Medicine; Mohammed Juboori, Department of Anesthesia Indiana University School of Medicine; Alexander Obukhov, Department of Cell Biology and Physiology; Fletcher White, Department of Anesthesia, Indiana University School of Medicine
Background/Significance/Rationale: There are 1.5 million new mild traumatic brain injuries (mTBI) annually in the US with many of those impacted experiencing long-term consequences months after the injury. Although the post injury mechanisms are not well understood, current knowledge indicates peripheral immune system activation as a causal link between mTBI and long-term side effects. Through a variety of mechanisms, peripheral innate immune cells are recruited to the CNS after TBI to repair and heal the injured tissue; however, the recruitment and activation of these cells leads to further inflammation. Emerging evidence suggest sympathetic nervous system (SNS) activity plays a substantial role in the recruitment of immune cells post injury.
Methods: Mice were given 3 mTBIs or 3 sham injuries and either immediately injected with 10 mg/kg propranolol or saline after each injury. Peripheral blood mononuclear cells (PBMCs) were isolated from blood and spleen of mice for flow cytometric analysis at 1-, 7-, and 28-days after the third injury.
Results/Findings: Our spleen and blood flow cytometry data depicts no monocyte population alterations 1 day post injury; however, mTBI derived PBMCs display increases in total, Ly6C+, and Ly6C- monocytes 1 week after injury. Interestingly, spleen mTBI mTBI derived MNCs displayed decreases in total monocytes with propranolol treated spleens displaying decreases in monocytic populations. 1 month after injury, propranolol treated mTBI PBMC have increased Ly6C- monocytes and decreased Ly6C+ monocytes compared to untreated mTBI PBMCs while the spleens have increased Ly6C+ monocytes.
Conclusions/Discussion: Our data display changes in the monocyte subpopulations in both the blood and spleen, most pronounced in the mTBI propranolol group.
Translational/Human Health Impact: These data indicate a single propranolol injection as a viable future mTBI therapy to reverse mTBI induced immunosuppression and potentially have beneficial long-acting effects.