title: Inflammation after trauma: microglial activation and traumatic brain injury.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Neuroscience, Department of Medicine, Imperial College London, Hammersmith Hospital Campus, London, UK.
authors.forename: Anil F
authors.initials: AF
authors.lastname: Ramlackhansingh
authors.forename: David J
authors.initials: DJ
authors.lastname: Brooks
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Greenwood
authors.forename: Subrata K
authors.initials: SK
authors.lastname: Bose
authors.forename: Federico E
authors.initials: FE
authors.lastname: Turkheimer
authors.forename: Kirsi M
authors.initials: KM
authors.lastname: Kinnunen
authors.forename: Steve
authors.initials: S
authors.lastname: Gentleman
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Heckemann
authors.forename: Karen
authors.initials: K
authors.lastname: Gunanayagam
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gelosa
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
mesh_terms: D000328:Adult; D000647:Amnesia / Q000209:etiology; D001930:Brain Injuries / Q000473:pathology* / Q000523:psychology; D016000:Cluster Analysis; D003072:Cognition Disorders / Q000473:pathology; D056324:Diffusion Tensor Imaging; D004522:Educational Status; D056344:Executive Function; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007249:Inflammation / Q000473:pathology*; D007546:Isoquinolines; D008262:Macrophage Activation; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D017628:Microglia / Q000473:pathology*; D008875:Middle Aged; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D013788:Thalamus / Q000473:pathology; D014888:Wechsler Scales
chemical_list: D007546:Isoquinolines; C037850:PK 11195