The Pathophysiology of Concussive Brain Injury

Bradley R Shane; Ann N Hoffman; Mayumi Prins; Christopher C Giza

doi:10.1016/j.csm.2025.06.002

The Pathophysiology of Concussive Brain Injury

Clin Sports Med. 2026 Apr;45(2):225-241. doi: 10.1016/j.csm.2025.06.002. Epub 2025 Jul 22.

Authors

Bradley R Shane¹, Ann N Hoffman², Mayumi Prins³, Christopher C Giza⁴

Affiliations

¹ David Geffen School of Medicine, UCLA Steve Tisch BrainSPORT Program; Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, USA; Department of Neurology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: bshane@mednet.ucla.edu.
² David Geffen School of Medicine, UCLA Steve Tisch BrainSPORT Program; Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA; Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA.
³ David Geffen School of Medicine, UCLA Steve Tisch BrainSPORT Program; Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA.
⁴ David Geffen School of Medicine, UCLA Steve Tisch BrainSPORT Program; Department of Pediatrics, University of California Los Angeles, Los Angeles, CA, USA; Department of Neurosurgery, University of California Los Angeles, Los Angeles, CA, USA.

PMID: 41786390
DOI: 10.1016/j.csm.2025.06.002

Abstract

Concussion is a complex brain injury affecting neurons and nonneuronal cells such as astrocytes, oligodendrocytes, microglia, and endothelial cells, leading to acute neurometabolic disturbances such as ionic imbalance and energy crisis. Beyond metabolism, these cellular responses may drive inflammation, blood-brain barrier disruption, neuroplasticity, glymphatic dysfunction, and neurodegeneration. Recognizing biological vulnerability and knowledge regarding repeat concussions has shaped protocols to prevent premature return to activity and reduce further injury risk. The concept of concussion and postconcussion endotypes, linking persistent symptoms to specific biological mechanisms, guides targeted diagnosis and treatment. Ongoing research into biomarkers and mechanisms aims to improve prognostication and develop personalized treatments for recovery.

Keywords: Axonal dysfunction; Biomarkers; Concussion; Endotypes; Neuroinflammation; Neurometabolic cascade; Persisting post-concussion symptoms (PPCS); Traumatic brain injury.

Publication types

Review

MeSH terms

Athletic Injuries* / physiopathology
Biomarkers
Blood-Brain Barrier / physiopathology
Brain Concussion* / diagnosis
Brain Concussion* / physiopathology
Brain Concussion* / therapy
Humans
Neuronal Plasticity

Substances

Biomarkers