The brain-bone marrow axis and its implications for chronic traumatic brain injury

Area of Science:

• Neuroscience
• Immunology
• Hematology

Background:

• Traumatic brain injury (TBI) disrupts systemic immune function, leading to neuroinflammation and neurodegeneration.
• The chronic effects of TBI on bone marrow (BM) hematopoietic stem/progenitor cells (HSPCs) and their impact on innate immunity and neurological outcomes remain unclear.

Purpose of the Study:

• To investigate the long-term consequences of TBI on BM HSPCs.
• To determine how TBI-induced changes in BM cells affect innate immunity and neurological function.

Main Methods:

• Bone marrow (BM) from TBI-injured or sham mice was transplanted into healthy irradiated hosts to create chimeric mice.
• Chimeric mice were analyzed for myeloid cell function, neurological deficits, and neuroinflammation at 8 weeks and 8 months post-transplantation.
• Gene expression analysis was performed to identify TBI-driven changes.

Main Results:

• Chimeric mice receiving BM from TBI donors (TBI→WT) exhibited myeloid cells with increased oxidative stress and reduced phagocytosis.
• At 8 months, TBI→WT mice showed leukopenia, persistent immune cell dysfunction, and neurological deficits.
• Gene expression revealed BM-driven neuroinflammation and neuropathology, with increased microgliosis and leukocyte infiltration correlating with longer reconstitution periods after secondary TBI.

Conclusions:

• TBI induces chronic activation and progressive dysfunction of the BM stem/progenitor cell pool.
• This dysfunction leads to long-term deficits in innate immunity and neurological function.
• TBI-associated BM alterations increase susceptibility to subsequent brain injury.