Propranolol attenuates systemic inflammatory response in aged traumatic brain injury patients

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Aged traumatic brain injury (TBI) patients have poorer prognoses due to poorly understood neuroinflammatory mechanisms.
• Aging significantly alters the neuroinflammatory response post-TBI.
• Propranolol, a beta-blocker, shows therapeutic potential in TBI but its effects in aged individuals are unclear.

Purpose of the Study:

• To investigate how propranolol modulates systemic inflammation in aged TBI mice.
• To explore the clinical effects of propranolol in aged TBI patients.
• To elucidate the mechanisms underlying propranolol's action in aged TBI.

Main Methods:

• Investigated propranolol's effects on inflammatory cell populations (neutrophils, monocytes) in aged TBI mice.
• Analyzed transcriptomic profiles of bone marrow and brain tissue from aged TBI mice.
• Conducted a retrospective clinical cohort study of aged TBI patients treated with propranolol.
• Performed transcriptomic and proteomic analyses on patient-derived samples (PBMCs, CSF).

Main Results:

• Propranolol reduced pro-inflammatory neutrophils and classical monocytes while expanding non-classical monocytes in aged TBI mice.
• Propranolol reversed inflammatory transcriptomic signatures in aged TBI mice, downregulating myeloid cell differentiation and inflammation pathways.
• Improved behavioral outcomes were observed in aged TBI mice treated with propranolol.
• Clinical data indicated attenuated systemic inflammation in aged TBI patients receiving propranolol.

Conclusions:

• Propranolol effectively modulates systemic inflammation in aged TBI.
• The drug reduces detrimental immune cell infiltration and reverses inflammatory gene expression.
• Propranolol demonstrates significant potential for improving outcomes in aged TBI patients by alleviating systemic inflammation.