Simple morphometry of axonal swellings cannot be used in isolation for dating lesions after traumatic brain injury.

Disruption of fast axonal transport as a result of traumatic brain injury is characterized by the accumulation of beta-amyloid precursor protein (APP) in axonal swellings. A recent report has suggested a correlation between the size of axonal swellings and survival time up to about 85 h after blunt head injury. The authors of the report concluded that this correlation, in conjunction with other evidence, might be useful in forensic science for timing injuries. To test this hypothesis we have used image analysis software to measure a number of different morphological parameters of axonal swellings. Paraffin sections from 63 cases of fatal head injury were stained with an antibody raised against the N-terminus of APP and counterstained with haematoxylin. Three different measurements were made of the APP-immunoreactive axonal swellings from the corpus callosum: (i) minimum and (ii) maximum Feret diameters, and (iii) area. Linear regression revealed a significant correlation between survival time and the minimum Feret diameter (p < 0.0001) and the area (p < 0.001) of axonal swellings. Our findings are in agreement with the previous study in that there is a significant correlation between axonal swelling size and survival time. However, we would suggest that the large variability in swelling size within individual cases and the heterogeneity of the original trauma seriously compromise the utility of such information in the timing of lesions.

Amyloid-beta peptide is toxic to neurons in vivo via indirect mechanisms.

We have studied the neurotoxicity of amyloid-beta (Abeta) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Abeta(1-42) compared to vehicle control and control peptide. At 5 months, there was a significant reduction in total cell numbers in the ganglion cell layer in Nissl stained retinas. There was glial cell dysfunction with upregulation of glial fibrillary acidic protein and a reduction in the expression of Müller cell associated proteins in the injected retinas. These results suggest an indirect cytotoxic effect of Abeta on retinal neurons and an important role for dysfunction of Müller glia in mediating Abeta neurotoxicity.