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R Gilberto González

Publications and source records attributed to R Gilberto González.

At least 19 recordsLinked to original sources
PubMed2005

Magnetic resonance spectroscopy reveals that activated monocytes contribute to neuronal injury in SIV neuroAIDS.

Difficulties in understanding the mechanisms of HIV neuropathogenesis include the inability to study dynamic processes of infection, cumulative effects of the virus, and contributing host immune responses. We used H magnetic resonance spectroscopy and studied monocyte activation and progression of CNS neuronal injury in a CD8 lymphocyte depletion model of neuroAIDS in SIV-infected rhesus macaque monkeys. We found early, consistent neuronal injury coincident with viremia and SIV infection/activation of monocyte subsets and sought to define the role of plasma virus and monocytes in contributing to CNS disease. Antiretroviral therapy with essentially non-CNS-penetrating agents resulted in slightly decreased levels of plasma virus, a significant reduction in the number of activated and infected monocytes, and rapid, near-complete reversal of neuronal injury. Robust macrophage accumulation and productive virus replication were found in brains of infected and CD8 lymphocyte-depleted animals, but no detectable virus and few scattered infiltrating macrophages were observed in CD8 lymphocyte-depleted animals compared with animals not receiving antiretroviruses that were sacrificed at the same time after infection. These results underscore the role of activated monocytes and monocyte infection outside of the brain in driving CNS disease.

AIDS Dementia Complex↗
PubMed2005

Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain.

PURPOSE: To elucidate the neuropathologic basis of transient changes in the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the primate brain by using a simian immunodeficiency virus (SIV)-infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome. MATERIALS AND METHODS: This study was approved by the Massachusetts General Hospital Subcommittee on Research and Animal Care and the Institutional Animal Care and Use Committee of Harvard University. Rhesus macaques infected with SIV were evaluated during the 1st month of infection. A total of 11 animals were studied, including four control animals, three animals sacrificed 12 days after infection, three animals sacrificed 14 days after infection, and one animal sacrificed 28 days after infection. All animals underwent in vivo proton ((1)H) magnetic resonance (MR) spectroscopy, and postmortem frontal lobe tissue was investigated by using high-spectral-resolution (1)H MR spectroscopy of brain extracts. In addition, quantitative neuropathologic analyses were performed. Stereologic analysis was performed to determine neuronal counts, and immunohistochemical analysis was performed to analyze three neuronal markers: synaptophysin, microtubule-associated protein 2 (MAP2), and calbindin. Analysis of variance (ANOVA) was used to determine substantial changes in neuropathologic and MR spectroscopic markers. Spearman rank correlations were calculated between plasma viral load and neuropathologic and spectroscopic markers. RESULTS: During acute infection with SIV, the macaque brain exhibited significant changes in NAA/Cr (P < .02, ANOVA) and synaptophysin (P < .013, ANOVA). There was no significant change in the concentration of Cr. No significant changes were found in neuronal counts or other immunohistochemical neuronal markers. With the Spearman rank test, a significant direct correlation was detected between synaptophysin and ex vivo NAA/Cr (r(s) = 0.72, P < .013). No correlation between NAA/Cr and neuronal counts, calbindin, or MAP2 was found. CONCLUSION: NAA/Cr is a sensitive marker of neuronal injury, not necessarily neuronal loss, and best correlates with synaptophysin, a marker of synaptodendritic dysfunction.

Animals↗
PubMed2005

Comparisons of brain metabolites observed by HRMAS 1H NMR of intact tissue and solution 1H NMR of tissue extracts in SIV-infected macaques.

The objective of this study was to compare ex vivo proton high-resolution magic angle spinning magnetic resonance spectra of intact tissue with those spectra obtained by solution (1)H NMR of brain extracts of the same sample. Sixteen brain tissue samples from simian immunodeficiency virus-infected rhesus macaques from both frontal cortex and putamen were evaluated by comparing brain metabolite quantities of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (MI), creatine (Cr), lactate (Lac), glutamate (Glu) and acetate (Ace). The ratios of the individual NMR peak areas of all metabolites relative to the creatine peak area were calculated. Linear regression analysis revealed significant correlations between measurements using the two methods. The strength of the correlations varied depending on the metabolite studied. We found highly significant correlations for NAA/Cr (r2 = 0.77; p < 0.0001), NAA + Ace/Cr (r2 = 0.73; p < 0.0001) and MI/Cr (r2 = 0.75; p < 0.0001). We observed somewhat less strong correlations for Glu/Cr (r2 = 0.54; p < 0.002) and Lac/Cr (r2 = 0.54; p < 0.002). There was a substantially weaker correlation for Cho/Cr (r2 = 0.32; p = 0.02). When plotting the metabolite ratios obtained by 1H HRMAS NMR of the intact tissue sample on the ordinate vs 1H NMR of the tissue extract on the abscissa, most metabolites exhibited a slope close to unity, and a positive intercept probably due to macromolecular contributions to the MAS spectra. The slope for Cho/Cr was substantially less than unity. Generally, samples from the frontal cortex showed a better correlation between intact and extracted tissue samples than putamen. This is most prominent in the cases of NAA/Cr and Cho/Cr. We conclude that both methods provide substantially the same information for most major brain metabolites, with the exception of the Cho resonance.

Animals↗
PubMed2005

Relationships between astrogliosis and 1H MR spectroscopic measures of brain choline/creatine and myo-inositol/creatine in a primate model.

BACKGROUND AND PURPOSE: In vivo 1H MR spectroscopy demonstrates elevated choline (Cho)/creatine (Cr) and myo-inositol (MI)/Cr in many neurologic diseases that has been ascribed to gliosis. We tested the hypotheses that in vivo Cho/Cr and/or MI/Cr levels are correlated with glial fibrillary acidic protein (GFAP) immunostains and that the changes are water-soluble metabolites. METHODS: We performed postmortem 1H MR spectroscopy and GFAP immunohistochemistry in brains from seven rhesus macaques acutely infected with simian immunodeficiency virus (SIV) and in four controls and compared the findings with previous in vivo MR spectroscopic results. Changes in neuropathologic and MR spectroscopic markers after infection and relationships among plasma viral load, GFAP immunostaining results, and ex vivo and in vivo MR spectroscopic measures were statistically evaluated. RESULTS: On GFAP immunostaining and in vivo MR spectroscopy, GFAP, Cho/Cr and MI/Cr were highest near the time of peak plasma viral load at 11 days postinfection (dpi). Immunostains returned to baseline by 14 dpi, whereas Cho/Cr and MI/Cr had different time courses, with the former dropping below baseline and the latter remaining elevated. Viral load and immunostains were significantly correlated. No correlation was found between ex vivo Cho/Cr or MI/Cr and viral load or between metabolite ratios from in vivo and ex vivo MR spectroscopy. CONCLUSION: In acute SIV infection, plasma viral load was significantly correlated with brain GFAP immunostains and in vivo 1H MR spectroscopic Cho/Cr. In vivo changes in Cho/Cr and MI/Cr were principally due to contributions other than those of low-molecular-weight water-soluble metabolites.

Animals↗
PubMed2004

A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS.

BACKGROUND: The neurological complications of HIV infection remain poorly understood. Clinically, in vivo 1H magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo 1H MRS study of the SIV/macaque model of neuroAIDS. RESULTS: Eight rhesus macaques were infected with SIVmac251 and serially imaged with MRI and 1H MRS to terminal AIDS or the endpoint of 2 years. During acute infection, there were stereotypical brain MRS changes, dominated by a significant elevation of the Cho/Cr ratio in the frontal cortex. Subsequently, brain metabolic patterns diverged between animals. There was an elevation of basal ganglia Cho/Cr four weeks post-inoculation in 2 animals that developed SIV encephalitis (p = 0.022). Metabolite ratios averaged across all 8 animals were not significantly different from baseline at any time point after 2 weeks post inoculation. However, linear regression analysis on all 8 animals revealed a positive correlation between a change in frontal lobe Cho/Cr and plasma viral load (P < 0.001, R = 0.80), and a negative correlation between NAA/Cr in the basal ganglia and the plasma viral load (P < 0.02, R = -0.73). No MRI abnormalities were detected at any time. CONCLUSIONS: After infection with SIV, macaque brain metabolism changes in a complex manner that is dependent on brain region, host factors and viral load. An elevation of basal ganglia Cho/Cr 4 weeks after SIV infection may be marker of a propensity to develop SIV encephalitis. Elevations of Cho/Cr, often observed in CNS inflammation, were associated with increased plasma viral load during acute and chronic infection. Evidence of neuronal injury in the basal ganglia was associated with increased plasma viral load in the chronic stage of infection. These observations support the use of drugs capable of controlling the viral replication and trafficking of virus into the CNS, and may help explain the reduction in incidence of HIV-associated dementia in the era of HAART despite the inability of most of those drugs to effectively enter the CNS.

AIDS Dementia Complex↗
PubMed2004

In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS.

The metabolic response of the rhesus macaque brain during acute simian immunodeficiency virus (SIV) infection was investigated with in vivo (1)H MR spectroscopy. Fifteen rhesus macaques were studied before inoculation, and once or twice after infection. In all, 13/15 macaques had elevations of Cho/NAA at 11-13 days postinoculation (dpi); all 10 macaques measured after 13 dpi had subsequent reduction of this ratio (ANOVA, P < 10(-6)). There were significant increases in Cho/Cr (20%, P = 0.04) and MI/Cr (14%, P = 0.003) at 11 dpi. At 13 dpi a 7.7% decrease (P = 0.02) in NAA/Cr was observed, while Cho/Cr was no longer significantly different from baseline. At 27 dpi Cho/Cr was decreased to 18% (P = 0.004) below preinoculation values, while NAA/Cr and MI/Cr were at baseline values. Absolute concentrations of Cho, MI, and NAA showed a similar time course, with no observed changes in Cr. There was a strong correlation between Cho/Cr change and plasma viral load (r(s) = 0.79, P < 0.01). Acute SIV produces extensive metabolic abnormalities in the brain, which may reflect inflammation and neuronal injury, which are reversed with immunological control of the virus. Similar events are likely to occur in acutely HIV-infected people, and may explain the neurobehavioral symptoms associated with acute HIV infection.

AIDS Dementia Complex↗
PubMed2004

Imaging NeuroAIDS.

Explore the source record for details and available documents.

AIDS Dementia Complex↗
PubMed2002

Noncontrast conventional computed tomography in the evaluation of acute stroke.

The advantages of CT scanning in the assessment of hyperacute stroke patients include convenience, accuracy, speed, and low cost. CT scanning is presently considered to be the standard of care for the detection of acute extra-axial and parenchymal hemorrhage, although newer MRI techniques are challenging this claim. The accuracy of CT scanning for stroke detection can be optimized by the use of appropriate scanning technique, as well as interactive image review at a picture archiving and communication system workstation using narrow window and level settings. More importantly, CT scanning has prognostic value for patients receiving thrombolytic treatment by helping to predict both responses to treatment and hemorrhage risk. Finally, as will be discussed in other articles in this issue, CT angiography can be performed in the same imaging session as noncontrast CT scanning without substantially increasing the time required for patient evaluation. This provides data regarding vascular patency and tissue perfusion, which are valuable in the triage of stroke patients.

Brain↗
PubMed2002

Diffusion MR imaging of acute ischemic stroke.

Diffusion MR imaging provides unique information about the physiologic state of ischemic tissue. It is highly sensitive and specific in the detection of acute and hyperacute ischemic stroke and has greatly improved the diagnosis and treatment of acute stroke. The DWI abnormality provides information about clinical outcome and final infarct size. Diffusion combined with perfusion MR imaging provides information about the operational ischemic penumbra and final infarct size. Diffusion MR imaging seems to be promising in the evaluation of candidates for thrombolysis.

Acute Disease↗
PubMed1996

Molecular and functional magnetic resonance neuroimaging for the study of dementia.

The living brain's structure, function, and underlying chemistry are increasingly being revealed in sharpened detail by the extraordinary evolution of magnetic resonance (MR) technology. Recent years have ushered in a wealth of new information about neurophysiology and pathological states owing to such technologies as functional MR imaging (fMRI), MR spectroscopy (MRS), and MR spectroscopic imaging (MRSI). These advances are of substantial benefit in the study of the dementias, especially Alzheimer's disease (AD). One primary objective of our laboratory at the Massachusetts General Hospital NMR Center is to utilize these extant and emerging MR technologies to further understanding of the human brain as it undergoes assault by AD. Our approach is guided by the belief that the pathological states observed in the AD brain must be accompanied by structural, chemical and/or physiological changes that can be made visible in an in vivo MR study. Quantitative measurements by MRI medical temporal lobe structures have been shown to be abnormal by several groups including our own. This use of MRI will be reviewed by others. In this paper, I will review recent advances in the application of MR for the study of chemical and functional brain abnormalities in dementia, and in particular to the investigation of AD.

Brain↗
PubMedDate not supplied

Functional CT perfusion imaging in predicting the extent of cerebral infarction from a 3-hour middle cerebral arterial occlusion in a primate stroke model.

BACKGROUND AND PURPOSE: Our purpose was to determine whether cerebral perfusion functional CT (fCT), performed after endovascular middle cerebral artery (MCA) occlusion, can be used to predict final cerebral infarction extent in a primate model. METHODS: fCT with bolus tracking was performed before and 30 and 150 minutes after 3-hour digital subtraction angiography (DSA)-guided endovascular MCA occlusion in five baboons. Parametric cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) maps were constructed by voxel-by-voxel gamma variate fitting and used to determine lesion sizes. Animals were sacrificed 48 hours after the occlusion, and ex vivo MR imaging was performed. Lesion sizes on fCT and MR images were compared. RESULTS: Hypoperfusion was clearly identified on all images obtained after MCA occlusion. Thirty and 150 minutes after occlusion onset, respectively, mean lesion sizes were 737 mm(2) +/- 33 and 737 mm(2) +/- 44 for CBF, 722 mm(2) +/- 32 and 730 mm(2) +/- 43 for CBV, and 819 mm(2) +/- 14 and 847 mm(2) +/- 11 for MTT. Mean outcome infarct size on MR images was 733 mm(2) +/- 30. Measurements based on CBV and CBF (R(2) = 0.97 and 0.96, P <.001), but not MTT (R(2) = 0.40, P >.5), were highly correlated with final lesion size. CONCLUSION: An endovascular approach to MCA occlusion provides a minimally invasive, reproducible animal model for controlled studies of cerebral ischemia and infarction. Derived cerebral perfusion maps closely predict the 48-hour infarct size after 3-hour MCA occlusion.

Angiography, Digital Subtraction↗