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 x 10(9) in controls to 18.3 x 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 micron3 and no sampled neurons were larger than 28,000 micron3. In addition, the absolute size distribution of neocortical neurons showed a significant decrease of the largest group of neurons by 50% (2p = 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.

[1]  S. Swindells,et al.  Platelet-activating factor: a candidate human immunodeficiency virus type 1-induced neurotoxin , 1994, Journal of virology.

[2]  E. Masliah,et al.  Cytokine receptor alterations during HIV infection in the human central nervous system , 1994, Brain Research.

[3]  G. D. Pearlson,et al.  Reduced basal ganglia volume in HIV‐1‐associated dementia , 1993, Neurology.

[4]  O. Selnes,et al.  Clinical‐neuropathologic correlation in HIV‐associated dementia , 1993, Neurology.

[5]  P. Lantos,et al.  Neuronal number and volume alterations in the neocortex of HIV infected individuals. , 1993, Journal of neurology, neurosurgery, and psychiatry.

[6]  J. Glass,et al.  Cytokine expression in the brain during the acquired immunodeficiency syndrome , 1992, Annals of neurology.

[7]  Herbert Budka,et al.  Neuropathology of Human Immunodeficiency Virus Infection , 1991, Brain pathology.

[8]  J. Glass,et al.  Intracerebral cytokine messenger RNA expression in acquired immunodeficiency syndrome dememtia , 1993, Annals of neurology.

[9]  C. Achim,et al.  Selective Neuronal Vulnerability in HIV Encephalitis , 1992, Journal of neuropathology and experimental neurology.

[10]  R. Gherardi,et al.  PATHOLOGY OF THE CENTRAL NERVOUS SYSTEM IN 40 CASES OF ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS) , 1988, Neuropathology and applied neurobiology.

[11]  L. Sharer,et al.  Pathology of HIV‐1 Infection of the Central Nervous System. A review , 1992, Journal of neuropathology and experimental neurology.

[12]  N. Kowall,et al.  Immunohistochemical patterns of selective cellular vulnerability in human cerebral ischemia , 1993, Journal of the Neurological Sciences.

[13]  G. Pearlson,et al.  Altered cortical blood flow in HIV‐seropositive individuals with and without dementia: a single photon emission computed tomography study , 1994, AIDS.

[14]  E. Masliah,et al.  Neocortical damage during HIV infection , 1991, Annals of neurology.

[15]  R. Rhodes.  Histopathologic features in the central nervous system of 400 acquired immunodeficiency syndrome cases: implications of rates of occurrence. , 1993, Human pathology.

[16]  P. Lantos,et al.  Assessment of neuronal density in the putamen in human immunodeficiency virus (HIV) infection. Application of stereology and spatial analysis of quadrats. , 1995, Journal of neurovirology.

[17]  G. Reynolds,et al.  Frontal cortex indoleamine-2,3-dioxygenase activity is increased in HIV-1-associated dementia , 1995, Neuroscience Letters.

[18]  J. Becker,et al.  Dementia in AIDS patients , 1993, Neurology.

[19]  E. Hirsch.  Why are nigral catecholaminergic neurons more vulnerable than other cells in Parkinson's disease? , 1992, Annals of neurology.

[20]  G D Pearlson,et al.  Magnetic resonance imaging measurement of gray matter volume reductions in HIV dementia. , 1995, The American journal of psychiatry.

[21]  I. Elovaara,et al.  A prospective radiologic and neurologic follow‐up study of 61 HIV‐1 ‐infected subjects: early beginning and slow progression of brain atrophy , 1997, European journal of neurology.

[22]  D. Troost,et al.  c‐Jun, JNK/SAPK Kinase and Transcription Factor NF-κB Are Selectively Activated in Astrocytes, but not Motor Neurons, in Amyotrophic Lateral Sclerosis , 1997, Journal of neuropathology and experimental neurology.

[23]  J. Glass,et al.  Stereological analysis of cerebral atrophy in human immunodeficiency virus-associated dementia. , 1996, Journal of neuropathology and experimental neurology.

[24]  K. Abe,et al.  Selective motor neuron death and heat shock protein induction after spinal cord ischemia in rabbits. , 1997, The Journal of thoracic and cardiovascular surgery.

[25]  T. Crawford,et al.  Cerebral white matter changes in acquired immunodeficiency syndrome dementia: Alterations of the blood‐brain barrier , 1993, Annals of neurology.

[26]  A. Guimarães,et al.  Brain choline-containing compounds are elevated in HIV-positive patients before the onset of AIDS dementia complex , 1996, Neurology.

[27]  Y. Ben-Ari,et al.  The HIV‐1 envelope protein GP120 induces neuronal apoptosis in hippocampal slices , 1996, Neuroreport.

[28]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[29]  P. Mehraein,et al.  Degeneration of the cerebellar dentate nucleus and the inferior olivary nuclei in HIV-1-infected brains: a morphometric analysis , 1996, Acta Neuropathologica.

[30]  J. Becker,et al.  Cognitive performance after progression to AIDS , 1995, Neurology.

[31]  J. Hugon,et al.  Calbindin D28K‐containing neurons, and not HSP70‐expressing neurons, are more resistant to HIV‐1 envelope (gp120) toxicity in cortical cell cultures , 1995, Journal of neuroscience research.

[32]  H. Gundersen,et al.  Six billion neurons lost in AIDS , 1995 .

[33]  C V Howard,et al.  The total number of neurons in the human neocortex unbiasedly estimated using optical disectors , 1990, Journal of microscopy.

[34]  B. Du,et al.  Direct cytotoxicity of HIV‐1 envelope protein gp120 on human NT neurons , 1996, Neuroreport.

[35]  P. Lantos,et al.  Neuronal loss in the frontal cortex in HIV infection , 1991, The Lancet.

[36]  J. Glass,et al.  Localization of HIV‐1 in human brain using polymerase chain reaction/in situ hybridization and immunocytochemistry , 1996, Annals of neurology.

[37]  P. Lantos,et al.  Neuronal pattern correlates with the severity of human immunodeficiency virus-associated dementia complex. Usefulness of spatial pattern analysis in clinicopathological studies. , 1996, The American journal of pathology.

[38]  P. Lantos,et al.  HIV‐Associated Disease of the Nervous System: Review of Nomenclature and Proposal for Neuropathology‐Based Terminology , 1991, Brain pathology.

[39]  B. Pakkenberg,et al.  No global neocortical nerve cell loss in brains from patients with senile dementia of Alzheimer's type , 1994, Neurobiology of Aging.