Inflammation after trauma: microglial activation and traumatic brain injury

Ann Neurol. 2011 Sep;70(3):374-83. doi: 10.1002/ana.22455. Epub 2011 Jun 27.


Objective: Patient outcome after traumatic brain injury (TBI) is highly variable. The underlying pathophysiology of this is poorly understood, but inflammation is potentially an important factor. Microglia orchestrate many aspects of this response. Their activation can be studied in vivo using the positron emission tomography (PET) ligand [11C](R)PK11195 (PK). In this study, we investigate whether an inflammatory response to TBI persists, and whether this response relates to structural brain abnormalities and cognitive function.

Methods: Ten patients, studied at least 11 months after moderate to severe TBI, underwent PK PET and structural magnetic resonance imaging (including diffusion tensor imaging). PK binding potentials were calculated in and around the site of focal brain damage, and in selected distant and subcortical brain regions. Standardized neuropsychological tests were administered.

Results: PK binding was significantly raised in the thalami, putamen, occipital cortices, and posterior limb of the internal capsules after TBI. There was no increase in PK binding at the original site of focal brain injury. High PK binding in the thalamus was associated with more severe cognitive impairment, although binding was not correlated with either the time since the injury or the extent of structural brain damage.

Interpretation: We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amnesia / etiology
  • Brain Injuries / pathology*
  • Brain Injuries / psychology
  • Cluster Analysis
  • Cognition Disorders / pathology
  • Diffusion Tensor Imaging
  • Educational Status
  • Executive Function
  • Female
  • Glasgow Coma Scale
  • Humans
  • Image Processing, Computer-Assisted
  • Inflammation / pathology*
  • Isoquinolines
  • Macrophage Activation
  • Magnetic Resonance Imaging
  • Male
  • Memory / physiology
  • Microglia / pathology*
  • Middle Aged
  • Neuropsychological Tests
  • Positron-Emission Tomography
  • Thalamus / pathology
  • Wechsler Scales


  • Isoquinolines
  • PK 11195