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. © 2011 American Neurological Association.

Ramlackhansingh, A., Brooks, D., Greenwood, R., Bose, S., Turkheimer, F., Kinnunen, K., et al. (2011). Inflammation after trauma: Microglial activation and traumatic brain injury. ANNALS OF NEUROLOGY, 70(3), 374-383 [10.1002/ana.22455].

Inflammation after trauma: Microglial activation and traumatic brain injury

GELOSA, GIORGIO
Penultimo
;
2011

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. 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. © 2011 American Neurological Association.
Articolo in rivista - Articolo scientifico
Adult; Amnesia; Brain Injuries; Cluster Analysis; Cognition Disorders; Diffusion Tensor Imaging; Educational Status; Executive Function; Female; Glasgow Coma Scale; Humans; Image Processing, Computer-Assisted; Inflammation; Isoquinolines; Macrophage Activation; Magnetic Resonance Imaging; Male; Memory; Microglia; Middle Aged; Neuropsychological Tests; Positron-Emission Tomography; Thalamus; Wechsler Scales; Neurology; Neurology (clinical)
English
2011
70
3
374
383
none
Ramlackhansingh, A., Brooks, D., Greenwood, R., Bose, S., Turkheimer, F., Kinnunen, K., et al. (2011). Inflammation after trauma: Microglial activation and traumatic brain injury. ANNALS OF NEUROLOGY, 70(3), 374-383 [10.1002/ana.22455].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/78631
Citazioni
  • Scopus 756
  • ???jsp.display-item.citation.isi??? 691
Social impact