Tentorial notch severity in the human brain: protocol, distribution and histology validation

In extreme cases of space-occupying lesions and elevated intracranial pressure, the dura has been documented to compress the brain, leading to trans-tentorial herniation. Even in individuals without traumatic brain injuries, edema or hydrocephalus, the tentorial cerebelli dura forms an impression, the tentorial notch (TN), on the surface of entorhinal cortex (EC). Given the EC’s role in memory formation and its known early vulnerability in Alzheimer’s disease, we aimed to determine whether the physical contact of the free edge of the tentorium cerebelli dura has a damaging effect on the tissue in non-injury related instances. We evaluated the severity of the TN on gross tissue ( n = 55 cognitive controls) and the effect of the indentation in histology-stained sections. We developed two novel protocols: (1) to differentiate among TN severity, and (2) to examine the impact of the TN on cortical layers and individual neurons in the EC in Nissl stained sections. We observed a TN in 96% of postmortem cases, suggesting it is an extremely common occurrence. To determine if the TN was present during life, we examined in vivo MRI of 22 young adults and report 95% exhibited a TN in at least one hemisphere (82% present in both hemispheres). The two independent datasets – the ex vivo (gross) dataset and in vivo (MRI) dataset – revealed same occurrence (96 and 95%), suggesting the notch is present in most adults. We observed cellular damage (defined as neuron loss, neuron stretching, and/or layer disruption) localized immediately superior and/or medial to the TN in 74% of samples histologically. TN severity correlated positively with cellular damage grade (Kendall’s coefficient = 0.65). This study brings together multiple types of data – independent datasets the Visible Human Project ® and 600 µm 3 in vivo MRI as well as postmortem gross surfaces with corresponding histology-stained sections to show evidence of the TN effect in tissue. Not only is the TN extremely common, but also it is linked to localized cellular damage, which warrants more investigation as a potential risk or possible comorbidity in this vulnerable region.