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Brain Advance Access published online on November 6, 2009

Brain, doi:10.1093/brain/awp264
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© The Author (2009). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Stereology of cerebral cortex after traumatic brain injury matched to the Glasgow Outcome Score

William L. Maxwell1, Mary-Anne MacKinnon2, Janice E. Stewart2 and David I. Graham2

1 Anatomy, Thomson Building, Institute of Biomedical and Life Sciences, Gilmorehill, Glasgow, G12 8QQ, UK 2 Academic Unit of Neuropathology, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital, 1345 Govan Road, Glasgow G53 4TF, UK

Correspondence to: William L Maxwell, ScD, Anatomy, Thomson Building, Institute of Biomedical and Life Sciences, Gilmorehill, Glasgow, G12 8QQ, UK E-mail: wmaxwell{at}bio.gla.ac.uk

Magnetic resonance imaging provides evidence for loss of both white and grey matter, in terms of tissue volume, from the cerebral hemispheres after traumatic brain injury. However, quantitative histopathological data are lacking. From the archive of the Department of Neuropathology at Glasgow, the cerebral cortex of 48 patients was investigated using stereology. Patients had survived 3 months after traumatic brain injury and were classified using the Glasgow Outcome Scale as follows: moderately disabled (n = 13), severely disabled (n = 12) and vegetative state (n = 12); and controls. Some patients from the archive were diagnosed with diffuse axonal injury post-mortem. Comparisons of changes in cortical neuron population across Glasgow Outcome Scale groups between diffuse axonal injury and non-diffuse axonal injury patients were undertaken using effect size analyses. The hypotheses tested were that (i) thinning of the cerebral cortex occurred after traumatic brain injury; (ii) changes in thickness of cortical layers in Brodmann areas 11, 10, 24a and 4 differed; and (iii) different changes occurred for neuronal number, their size and nearest neighbour index across Glasgow Outcome Scale groups. There was a greater loss of large pyramidal and large non-pyramidal neurons with a more severe score on the Glasgow Outcome Scale from all four cortical regions, with the greatest loss of neurons from the prefrontal cortex of patients with diffuse axonal injury. There were differences in the changes of number of medium and small pyramidal and non-pyramidal neurons between different cortical regions, and between patients with and without diffuse axonal injury. Generally, a decrease in the somatic diameter of pyramidal and non-pyramidal neurons was associated with a more severe clinical outcome. However, in the motor cortex a more severe Glasgow Outcome Scale was associated with an increased diameter of medium pyramidal neurons and small non-pyramidal cells. Pyramidal and non-pyramidal neurons did not follow a Poisson distribution within the neuropil of control patients. Pyramidal neurons were usually scattered while medium and small non-pyramidal neurons were clustered. An increased spacing between remaining neurons usually occurred across Glasgow Outcome Scale groups. It is concluded that loss of neurons resulted in reduced executive and integrative capability in patients after traumatic head injury.

Key Words: cortical neurons; head injury; stereology

Abbreviations: BA, Brodmann area; CI, confidence interval; DAI, diffuse axonal injury; DTI, diffusion tensor imaging; GOS, Glasgow Outcome Score; NNI, nearest neighbour index; NND, nearest neighbour distance; non-DAI, patient without diffuse axonal injury

Received December 22, 2008. Revised August 4, 2009. Accepted September 12, 2009.


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