Preferential loss of large neocortical neurons during HIV infection: a study of the size distribution of neocortical neurons in the human brain

The infection with human immunodeficiency virus (HIV) is associated with a global and severe loss of neocortical neurons. However, there is limited knowledge concerning whether all neurons are equally susceptible to damage during HIV infection. Other studies have reported low vulnerability of small interneurons and high vulnerability of large motor neurons. Thus, it is natural to suggest that HIV infection, which causes damage to neurons in several ways, may predominantly affect large neurons in the neocortex. In this study we have used three unbiased stereological probes: Cavalieri's principle, the optical dissector and the rotator method, to obtain both total neocortical neuron number and their size distribution in formalin-fixed brains from six male acquired immunodeficiency syndrome (AIDS) patients and six male controls. The material is a selection of a large material choosing the youngest. The number of neurons in neocortex was reduced by 25% from 24.4×10 9 in controls to 18.3×10 9 in the AIDS patients; the reduction is similar to that of 27% found in the large material. In the normal size distribution of the neocortical neurons most neurons were smaller than 5000 μm 3 and no sampled neurons were larger than 28,000 μm 3. In addition, the absolute size distribution of neocortical neurons showed a significant decrease of the largest group of neurons by 50% (2 p=0.01) in the AIDS group, while there was no significant difference between controls and AIDS patients in the number of small neurons. The pattern of reduction in the number of large neocortical neurons was found in frontal, temporal, parietal as well as in occipital regions. This suggests that large neurons are more sensitive than small neurons to the destruction caused by the HIV infection.