Inflammation after trauma: Microglial activation and traumatic brain injury
Article first published online: 27 JUN 2011
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 70, Issue 3, pages 374–383, September 2011
How to Cite
Ramlackhansingh, A. F., Brooks, D. J., Greenwood, R. J., Bose, S. K., Turkheimer, F. E., Kinnunen, K. M., Gentleman, S., Heckemann, R. A., Gunanayagam, K., Gelosa, G. and Sharp, D. J. (2011), Inflammation after trauma: Microglial activation and traumatic brain injury. Ann Neurol., 70: 374–383. doi: 10.1002/ana.22455
- Issue published online: 8 SEP 2011
- Article first published online: 27 JUN 2011
- Accepted manuscript online: 18 APR 2011 08:40AM EST
- Manuscript Accepted: 8 APR 2011
- Manuscript Revised: 1 APR 2011
- Manuscript Received: 5 JAN 2011
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.
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.
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.
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. ANN NEUROL 2011;