Cerebral amyloid angiopathy in traumatic brain injury: association with apolipoprotein E genotype

Objective: In view of the association of the apolipoprotein E (APOE) {varepsilon}4 allele with poor outcome after traumatic brain injury we determined the frequency of cerebral amyloid angiopathy (CAA) and the extent of haemorrhagic pathology in relation to APOE genotype in an autopsy series of 88 head injured cases.Methods: Tissue sections from the frontal and temporal lobes were immunostained for amyloid-ß peptide (Aß) and stained for Congo red to identify vascular amyloid pathology. A semiquantitative assessment of contusions, the total contusion index, was used to estimate the severity of the haemorrhagic pathology. APOE genotypes were determined by polymerase chain reaction of genomic DNA extracted from paraffin embedded tissue sections.Results: CAA was present in 7/40 (18%) {varepsilon}4 carriers compared with 1/48 (2%) non-{varepsilon}4 carriers (p = 0.021, 95% confidence interval (CI) for difference in proportions with CAA 3% to 29%) with 6/40 (4 with CAA) {varepsilon}4 carriers being homozygotes. Thus the risk of having CAA for {varepsilon}4 carriers was 8.4 times that for the non-{varepsilon}4 carriers. However, there was no clear tendency for patients with CAA to have more severe or more numerous contusions (median contusion index 19 (CAA) v 14.5, p = 0.23, 95% CI for difference in medians –5 to 14).Conclusions: Presence of CAA in head injured cases was significantly associated with possession of an APOE {varepsilon}4 allele but not with the severity of contusions

Topography of axonal injury as defined by amyloid precursor protein and the sector scoring method in mild and severe closed head injury

Published in Volume: 12 Issue 4: January 29, 2009Abstract not availablePeter C. Blumbergs, Grace Scott, Jim Mana Vis, Helen Wainwright, Donald A. Simpson, A. Jack Mclea

The neuroinflammatory response in humans after traumatic brain injury

Aims: Traumatic brain injury is a significant cause of morbidity and mortality worldwide. An epidemiological association between head injury and long-term cognitive decline has been described for many years and recent clinical studies have highlighted functional impairment within 12 months of a mild head injury. In addition chronic traumatic encephalopathy is a recently described condition in cases of repetitive head injury. There are shared mechanisms between traumatic brain injury and Alzheimer's disease, and it has been hypothesized that neuroinflammation, in the form of microglial activation, may be a mechanism underlying chronic neurodegenerative processes after traumatic brain injury.Methods: This study assessed the microglial reaction after head injury in a range of ages and survival periods, from <24-h survival through to 47-year survival. Immunohistochemistry for reactive microglia (CD68 and CR3/43) was performed on human autopsy brain tissue and assessed ‘blind’ by quantitative image analysis. Head injury cases were compared with age matched controls, and within the traumatic brain injury group cases with diffuse traumatic axonal injury were compared with cases without diffuse traumatic axonal injury.Results: A major finding was a neuroinflammatory response that develops within the first week and persists for several months after traumatic brain injury, but has returned to control levels after several years. In cases with diffuse traumatic axonal injury the microglial reaction is particularly pronounced in the white matter.Conclusions: These results demonstrate that prolonged microglial activation is a feature of traumatic brain injury, but that the neuroinflammatory response returns to control levels after several years