A longitudinal study of brain volume changes in rhesus macaque model infected with SIV.

Given the current lack of understanding of brain volume changes caused by HIV infection, this study aimed to longitudinally assess the changes in regional brain tissue volume following HIV infection and to explore its relationship with peripheral blood absolute CD4+ lymphocyte count (CD4+), the percentage of monocytes in plasma(MON%) and cerebrospinal fluid viral load (CFVL).Four adult male rhesus monkeys were examined in healthy status and following infection with simian immunodeficiency virus using high-resolution 3D T1-weighted sagittal whole brain magnetic resonance imaging. DPABI and SPM were used to process and record changes in brain tissue volume. Correlation analyses were then used to explore the above relationships. Compared with brain tissue volume during the healthy stage, there was no change at 12 and 24 weeks postinoculation (12 wpi, 24 wpi). At 36 wpi, 48 wpi, and 60 wpi, basal ganglia, left inferior temporal gyrus, left occipital gyrus, and left superior frontal gyrus exhibited varying degrees of atrophy. There was no association found between CD4+, MON%, CFVL, and brain volume loss in any brain region. Our research demonstrated that in the early stage of HIV infection, local brain tissue atrophy can be demonstrated by MRI technique; furthermore, MRI can identify the earliest site of atrophy as well as the most severely affected site. Although there was no significant correlation between brain tissue volume loss and CD4+, MON%, and CFVL, our findings provided some evidence in the application of volumetric MR imaging in the early diagnosis and treatment follow-up of patients with HIV infection.

Development of somatostatin immunoreactive neurons in the rat occipital cortex: a combined immunocytochemical-autoradiographic study.

The postnatal development of somatostatin (SRIF)-immunoreactive neurons, previously labeled with [3H]thymidine on embryonic days E14-E22, has been studied in the rat occipital cortex. Immunocytochemistry combined with autoradiography showed an "inside-out" maturation pattern. Only SRIF neurons generated at E14 were present in layer VI in newborn rats. Later generated SRIF neurons appeared progressively higher in the cortex until about postnatal day 12 when SRIF neurons from E21 appeared in layer II. At 2 weeks of age, therefore, all SRIF neurons from E14-E21 were present. Most of these had been generated between E15 and E17 with a moderate number at E14 and rapidly diminishing numbers from E18 to E21. Although an overall layered distribution was apparent at peak production, there was a tendency for diffuse distribution most noticeable at E17. Diffusely distributed neurons were more likely to be below their appropriate layer than above it, thus contributing extra SRIF neurons to layer VI. At 3, 4, and 5 weeks, progressively fewer SRIF neurons were seen with a consequent reduction in the number of double-labeled neurons. It is suggested that the transient population of SRIF neurons thus revealed plays a role in cortical development.

Neuron-binding antibodies in Alzheimer's disease and Down's syndrome.

We used an indirect immunoperoxidase technique (Avidin-Biotin system) to study the sera of patients with "clinically probable" Alzheimer's disease (AD) and with Down's Syndrome (DS), compared with age-matched controls. Diluted sera were incubated with paraffin sections of hippocampus, frontal, temporal, and parieto-occipital lobes from normal human brains. Biotinylated anti-human goat gamma-globulins were used as secondary antisera. A significantly greater percentage of neurons were immunostained in all the brain regions (frontal, temporal, and parieto-occipital lobes and hippocampus) incubated with sera of AD patients than with sera of DS patients or of controls. This indicates that AD patients have an excess of circulating neuron-binding antibodies (NBAs), mainly reacting with cytoplasmic structures. NBAs could be either the cause or the result of the cerebral lesion found in AD. This study is not able to answer this question, but some previous data from our own and other laboratories suggest that NBAs have a role in the pathogenesis of AD lesions. Since we found no increase of NBAs in DS patients, the brain lesions in DS appear to have a different pathogenesis.

Asymmetrical modulation of immune reactivity in left- and right-biased rats after ipsilateral ablation of the prefrontal, parietal and occipital brain neocortex.

We report here on the lateralized brain immunomodulation in male Wistar rats, a phenomenon related to the rotational bias of animal and the site of cortical lesion. Rats assigned to left- and right-rotators in a cylindrical Plexiglass rotometer were subjected to the ablation of the ipsilateral prefrontal cortex (PFC), parietal cortex (PC) and occipital cortex (OC) and sensitized with bovine serum albumin (BSA) in complete Freund's adjuvant. Intact and sham-lesioned left-biased animals demonstrated increased Arthus and delayed hypersensitivity skin reactions and antibody production to BSA in comparison with corresponding right-biased animals. PFC ablation decreased humoral and cellular immune responses to BSA in left- but increased in right-biased rats. Lesioning of PC decreased humoral immune reactions in left- but increased in right-rotating animals. OC ablation failed to produce immunological abnormalities. These results suggest that immunopotentiation is associated with the left neocortex, and immunosuppression with the right neocortex. The prefrontal cortex appears to be particularly associated with immune reactions.

The pathology of Rasmussen syndrome: stages of cortical involvement and neuropathological studies in 45 hemispherectomies.

PURPOSE: Rasmussen syndrome (RS) is a rare form of epilepsy characterized by progressive destruction of a single hemisphere. To characterize the profile of cortical involvement in RS, we studied the pathological changes in the cerebral cortex of 45 hemispherectomies performed at Johns Hopkins Hospital between 1985 and 2002. METHODS: The patterns of pathologic changes and stages of cortical abnormalities were studied by histology and immunocytochemistry methods. The burden of pathology (BP) was quantified in all brain regions of each of the 45 hemispheres. RESULTS: Our study demonstrated significant heterogeneity in the stages of cortical pathology and the multifocal nature of the disease. These stages varied from early inflammation defined by infiltration of T lymphocytes and neuroglial reactions, to more severe stages with extensive neuronal cell death and cavitation of the cerebral cortex. A greater BP was significantly associated with an early age at onset (p = 0.01) and longer duration of disease (p < or = 0.001). The BP was similar in all brain regions except the occipital lobe, where the BP was significantly lower (p = 0.032). CONCLUSIONS: The multifocal distribution of pathologic changes, as well as the heterogeneity in the stages of cortical damage in each patient, is consistent with an ongoing and progressive immune-mediated process of neuronal damage that involves neuroglial and lymphocytic responses, resembling other autoimmune CNS disorders such as multiple sclerosis.