Aspects of immune and inflammatory response in mumps meningoencephalitis: cytokines quantification

Abstract

The acquired immunodeficiency syndrome (AIDS) presents, in most of the cases, neurological complications due either to the direct neurotoxic effect of the human immunodeficiency virus (HIV) or secondary to neoplasms and opportunistic infections. Among the former, the most frequent is the AIDS-associated cognitive/ motor complex, which has been correlated to the appearance of cerebral atrophy, although the type and extent of neuronal suffering remain a controversial issue. Recent quantitative studies have shown a remarkable loss of neocortical neurons, while others, using traditional quantification techniques, have not found cell death in the hippocampal formation (HF). Taking into account the frequency of cognitive symptoms in AIDS patients, we decided to study the HF in this condition, as this region plays an important role in the processing of the cognitive information, namely in learning and memory. To evaluate the immunological behavior of the central nervous system, which is considered a sanctuary organ of the immune system and a possible virus reservoir, the cerebospinal fluid (CSF) of seropositive patients was also studied.The morphometric study of the HF was performed in necropsic material from two groups of male adults: 10 infected by HIV-1 and 10 age-matched individuals, whose material was used as control. Unbiased stereological methods, namely the optical disector and the fractionator, were used to estimate the total number of neurons from the major HF subdivisions: granule cell layer and hilus of the dentate fascia and the pyramidal cell layers of CA3 and CA1 regions of the hippocampus. The volumes of each subdivision, including the non-cellular layers, were calculated by applying the Cavalieri's principle. The mean neuronal nuclear and somatic volumes from the same neuronal populations were measured by the nucleator. Besides, in order to appreciate the HF cytoarquitectonical characteristics, the neuronal dendritic arborizations of those cells were qualitative and quantitatively studied using the Golgi method. This study was extended at the immunohistochemical level to better evaluate the neuronal degenerations (ubiquitine) and the gliosis (GFAB). We found a significant volumetric reduction in all HF subdivisions in AIDS patients, but without cell death. Nevertheless, the neuronal mean nuclear and somatic volumes were always lower in that group. Besides, important dendritic changes were observed in AIDS in all arborizations studied; these changes were more apparent in hilar basket cells and in CA3 pyramids. A reduction of the dendritic spine density in the granule cells and in the basal arborizations of the CA3 and CA1 pyramids was found. The immunohistochemical study did not reveal any changes between AIDS patients and controls.The CSF analysis showed cellular and humoral abnormalities, irrespective of the clinical appearance of the neurological involvement, traducing intrathecal immune activation.The marked HF cytoarchitectonical changes found in HIV encephalopathy contribute to explain the dementi...