AIDS does not alter the total number of neurons in the hippocampal formation but induces cell atrophy: a stereological study (original) (raw)
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Dendritic changes in the hippocampal formation of AIDS patients: a quantitative Golgi study
Acta Neuropathologica, 2004
We have previously shown that in the hippocampal formation of patients with acquired immunodeficiency syndrome (AIDS) there is neuronal atrophy, without cell loss. Because reductions in neuronal size are suggestive of associated neuritic alterations, we decided to study the dendritic trees of the main neuronal populations in the hippocampal formation. Material was obtained in five male AIDS patients and five male controls. After Golgi impregnation, the dendritic arborizations of dentate granule and hilar basket cells, and of CA3 and CA1 pyramidal cells, were hand traced, and their segments classified, counted and measured. We found an impoverishment of the dendritic trees in all neuronal populations in the AIDS group, which was more striking in the hilus and CA3 field. Specifically, hilar neurons had fewer dendritic segments, and reduced branching density and dendritic extent; in CA3 pyramids there was a decrease in the number of terminal segments in the basal trees, and a reduction in the total number of segments, number of medium order terminals, dendritic branching density and dendritic extent in the apical trees. In CA1 pyramids, the terminals were shorter in the apical trees and the dendritic spine density decreased in the basal trees, whereas in granule cells only the dendritic spine density was reduced in AIDS patients. Subtle signs suggestive of dendritic reorganization were observed. These results point to a regional vulnerability of the hippocampal formation to HIV infection, and might contribute to explaining the occurrence of dementia, as a consequence of overall reduction in the hippocampal neuronal receptive surface.
Brain Research, 1999
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 Ž. 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 mm 3 and no sampled neurons were larger than 28,000 mm 3. In addition, the absolute size distribution of neocortical neurons showed a significant Ž. decrease of the largest group of neurons by 50% 2 p s 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.
Reduced basal ganglia volume in HIV-1-associated dementia: Results from quantitative neuroimaging
Neurology, 1993
Although brain atrophy is a common neuroradiologic and pathologic finding in patients with HIV-1 infection, especially those with HIV-1-associated dementia complex, it is not clear whether specific regions of the brain are differentially responsible for tissue loss. In this study, we measured volumes of basal ganglia structures on MRIs for three groups: HIV-1-infected homosexual men with HIV-1-associated dementia complex (HIV+ demented), HIV-1infected homosexual men without HIV dementia (HIV+ nondemented), and noninfected homosexual men. All groups were comparable on age and years of education, and the HIV+ groups were comparable on level of immunosuppression. Total brain volume was smaller in the HIV+ nondemented patients in comparison with HIV-control subjects; the HIV+ demented patients demonstrated even smaller brain volumes than the HIV+ nondemented patients. Smaller basal ganglia volumes, after corrections for intracranial volume, distinguished HIV+ demented patients from the other two groups; there were no differences between the HIV+ nondemented and HIV-groups on basal ganglia volumes. This study suggests that HIV infection causes generalized brain atrophy, but that the clinical features of HIV dementia develop with selective basal ganglia atrophy, consistent with the characterization of HIV dementia as subcortical.
Neurobiology of Aging, 2014
Advances in treatment have transformed HIV infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were studied using 351 MRIs and a battery of neuropsychological tests collected two or more times over follow-up periods ranging from 6 months to 8 years. Brain tissue regions of interest showed expected age-related decrease in volume; CSF-filled spaces showed increase in volume for both groups. Although HIV infected individuals were in good general health, and free of clinicallydetectable dementia, several brain regions supporting higher-order cognition and integration of functions showed acceleration of the normal aging trajectory, including neocortex, which extended from the frontal and temporal poles to the parietal lobe, and the thalamus. Beyond an anticipated increase in lateral ventricle and Sylvian fissure volumes and decrease in tissue volumes (specifically, the frontal and sensorimotor neocortices, thalamus, and hippocampus) with longer duration of illness, most regions also showed accelerated disease progression. This accelerated loss of cortical tissue may represent a risk factor for premature cognitive and motor compromise if not dementia. On a more promising note, HIV-infected patients with increasing CD4 counts exhibited slower expansion of Sylvian fissure volume and slower declines of frontal and temporoparietal cortices, insula, and hippocampus tissue volumes. Thus, attenuated shrinkage of these brain regions, likely with adequate pharmacological treatment and control of further infection, has the potential of abating decline in associated, higher-order functions, notably, explicit memory, executive functions, self-regulation, and visuospatial abilities.
Magnetic resonance imaging measurement of gray matter volume reductions in HIV dementia
The American journal of psychiatry, 1995
The authors recently reported smaller basal ganglia volumes for patients with HIV-associated dementia than for HIV-infected patients without dementia and a seronegative comparison group. The purpose of the current study was to determine whether HIV dementia is associated with volume reductions in other brain regions. The authors measured volumes of CSF and gray and white tissue on cranial magnetic resonance images from homosexual men who were 1) infected with HIV with HIV-associated dementia complex, 2) infected with HIV without dementia, and 3) HIV seronegative. Results suggest that loss of white matter occurs with HIV infection and is more severe in HIV-positive patients with dementia than in those without dementia. There was some generalized volume reduction in gray matter in HIV-positive demented patients, although group differences did not reach significance when adjusted for age. Volume of posterior cortex, however, was significantly smaller among HIV-positive patients with de...
Acta Neuropathologica, 1990
The encephalopathy resulting from direct infection of the brain by human immunodeficiency virus (HIV), which correlates clinically with the AIDS dementia complex, has been reported as being localized to the white matter where it induces myelin loss, gliosis and perivascular infiltration by mononuclear macrophages and multinucleated giant cells. Damage to the cortical grey matter in HIV encephalopathy was investigated in nine randomly selected HIV-positive cases with or without clinical or morphological evidence of encephalopathy and in five age-matched controls, using routine histology and immunohistochemical methods [glial fibrillary acidic protein (GFAP), microglia and HIV antibodies]. Increased numbers of GFAP-expressing astrocytes and Ricinus communis agglutinin 1-120-expressing microglial cells were found in all the HIV-positive cases (including asymptomatic) and their severity could be correlated with the severity of the encephalopathy in the white matter; the increase in number of cells expressing GFAP was diffuse and the intensity of the staining higher than that of microglial cells. The subpial region was the most severely involved. It is suggested that involvement of the cortical grey matter is more common in HIV infection than previously suspected and that clinical evidence of a dementing process in AIDS is not necessarily due only to white matter lesions.
The effects of HIV and aging on subcortical shape alterations: A 3D morphometric study
Human Brain Mapping, 2016
Standard volumetric neuroimaging studies have demonstrated preferential atrophy of subcortical structures among individuals with HIV. However, to our knowledge, no study has investigated subcortical shape alterations secondary to HIV and whether advancing age impacts that relationship. This study employed 3D morphometry to examine the independent and interactive effects of HIV and age on shape differences in nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus in 81 participants ranging in age from 24-76 including 59 HIV+ individuals and 22 HIV-seronegative controls. T1-weighted MRI underwent a pre-processing pipeline followed by automated subcortical segmentation. Parametric statistical analyses were used to determine independent effects of HIV infection and age on volume and shape in each region of interest (ROI) and the interaction between age and HIV serostatus in predicting volume/ shape in each ROI. Significant main effects for HIV were found in the shape of right caudate and nucleus accumbens, left pallidum and hippocampus. Age was associated with differences in shape in left pallidum, right nucleus accumbens and putamen, and bilateral caudate, hippocampus and thalamus. Of greatest interest, an age*HIV interaction effect was found in the shape of bilateral nucleus accumbens, amygdala, caudate, and thalamus as well as right pallidum and putamen such that increasing age in HIV participants was associated with greater shape alterations. Traditional volumemetric analyses revealed main effects for both HIV and age but no age*HIV interaction.
Hippocampus, 2008
The human immunodeficiency virus type 1 (HIV-1) proteins, gp120 and Tat, are believed to play a role in mediating central nervous system (CNS) pathology in HIV-1 infected patients. Using design-based stereology, we examined the role of neonatal intrahippocampal injections of gp120 and Tat on the adult hippocampus ($7½ month). Postnatal day (P)1-treated Sprague-Dawley rats were bilaterally injected with vehicle (VEH, 0.5 ll sterile buffer), gp120 (100 ng), Tat (25 lg) or combined gp120 1 Tat (100 ng 1 25 lg). Using Nissl-stained tissue sections, we quantified total neurons in five subregions of the rat hippocampus [granual layer (GL), hilus of the dentate gyrus (DGH), cornu ammonis fields (CA)2/3, CA1, and subiculum (SUB)], and total glial cells (astrocytes and oligodendrocytes) in two subregions (DGH and SUB). Estimates of cell area and cell volume were taken in the DGH. There was a significant reduction of neuron number in the CA2/3 subfield by Tat and gp120, and a significant reduction in the DGH by Tat only. For glial cells, numbers of astrocytes in the DGH and SUB were increased by the Tat protein, whereas no effects were noted for gp120. Finally, for oligodendrocytes Tat increased cell number in the DGH but not in any other region; gp120 had no detectable effect in any brain region. Estimates of cell area and cell volume of the three different cell types revealed no significant differences between treatments. Collectively, these results suggest differential effects of gp120 and Tat on the estimated total number of neurons, as well as on the number of glial cells. V V C 2007 Wiley-Liss, Inc.
Topographies of cortical and subcortical volume loss in HIV and aging in the cART era
Journal of acquired immune deficiency syndromes (1999), 2016
Studies of HIV-associated brain atrophy often focus on a priori brain regions of interest, which can introduce bias. A data-driven, minimally-biased approach was used to analyze changes in brain volumetrics associated with HIV and their relationship to aging, viral factors, and combination antiretroviral therapy (cART), as well as gender and smoking. A cross-sectional study of 51 HIV-uninfected (HIV-) and 146 HIV-infected (HIV+) participants. Structural MRI of participants was analyzed using principal component analysis (PCA) to reduce dimensionality and determine topographies of volumetric changes. Neuropsychological (NP) assessment was examined using global and domain-specific scores. The effects of HIV disease factors (e.g. viral load, CD4, etc.) on brain volumes and NP were investigated using penalized regression (LASSO). Two components of interest were visualized using PCA. An aging effect predominated for both components. The first component, a cortically-weighted topography, ...