Neural Regeneration Research ›› 2026, Vol. 21 ›› Issue (10): 4578-4593.doi: 10.4103/NRR.NRR-D-25-00902

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Mild and repetitive mild traumatic brain injury: Changes in microglial cells and synapses

Adna Smajkan1, 2, 3, #, Elizabeth Naranjo-Cinto1, 2, 4, #, Florence M. Bareyre1, 2, 5, *   

  1. 1Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, Munich, Germany; 
    2Biomedical Center Munich (BMC), Medical Faculty, LMU Munich, Planegg-Martinsried, Germany; 
    3Graduate School of Systemic Neurosciences, Ludwig-Maximilians-Universitaet Muenchen, Planegg-Martinsried, Germany; 
    4Elite MSc. Biomedical Neuroscience, Technische Universitaet Muenchen, Munich, Germany; 
    5Munich Cluster of Systems Neurology (SyNergy), Munich, Germany
  • Online:2026-10-15 Published:2026-06-11
  • Contact: Florence M. Bareyre, PhD, Florence.bareyre@med.uni-muenchen.de.
  • Supported by:
    This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG): TRR274 Project ID 408885537; Munich Center for Systems Neurology (SyNergy; EXC 2145 / ID 390857198) and FOR 5705 (BA 4140/2-1) (all to FMB).

Abstract: Mild traumatic brain injury results from external mechanical forces to the head. Repetitive mild traumatic brain injury, characterized by multiple concussive events over time, is increasingly recognized in contact sports or domestic abuse. Repetitive injuries are associated with a greater risk of cumulative deficits and chronic neurodegenerative conditions. After a period of large focus on gross morphological changes following mild traumatic brain injury and repetitive mild traumatic brain injury, recent research is exploring more subtle yet critical changes at the synaptic and microglial levels. Novel findings indicate that even a single mild traumatic brain injury can induce transient alterations in synaptic function, including increased excitatory neurotransmission and disrupted synaptic plasticity. Parallel to synaptic changes, microglial cells, the brain’s resident immune cells, undergo rapid and prolonged activation after mild traumatic brain injury, including morphological transformation and functional activation. In repetitive mild traumatic brain injury, microglial priming is more pronounced, leading to sustained neuroimmune dysregulation and heightened and persistent vulnerability. In this review, we will summarize the current literature on mild traumatic brain injury and repetitive mild traumatic brain injury with a specific emphasis on microglial and synaptic changes.

Key words: animal models, biomarkers, concussion, connectivity, microglia cells, microglia-mediated synapse engulfment, repetitive concussion, synapse loss