Journal of neurovirology
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Journal of neurovirology · May 2008
Differential transcription of matrix-metalloproteinase genes in primary mouse astrocytes and microglia infected with Theiler's murine encephalomyelitis virus.
The BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) induces demyelinating disease in susceptible mice comparable to human multiple sclerosis. Recent in vivo studies showed that matrix metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of MMPs, TIMPs) are associated with demyelination in Theiler's murine encephalomyelitis. The present study was performed to evaluate the in vitro MMP and TIMP expression in astrocytes and microglia following TMEV infection. ⋯ MMP-3, -9, -10, -12, and -13 as well as TIMP-1 were the enzymes most prominently up-regulated in TMEV-infected astrocytes. In contrast, TMEV infection was associated with a down-regulation of MMPs and TIMPs in microglia. Conclusively, in addition to inflammatory infiltrates, TMEV-induced astrocytic MMPs might trigger a proteolysis cascade leading to an opening of the blood-brain barrier and demyelination in vivo.
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Journal of neurovirology · Dec 2007
Anterograde transsynaptic tracing in the murine somatosensory system using Pseudorabies virus (PrV): a "live-cell"-tracing tool for analysis of identified neurons in vitro.
The Pseudorabies virus (PrV) strain Bartha is widely used as a tool for retrograde transneuronal tracing in mammals. Traced neurons can be identified in cell culture allowing the analysis of their physiological features ("live-cell"-tracing). ⋯ Following intranasal application in mice, labelled trigeminal and brainstem neurons could be identified in vitro. Detailed electrophysiological analysis indicated that viral infection did not affect neuronal properties, making PrV-Kaplan eligible for functional analysis of identified neurons within somatosensory systems.
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Journal of neurovirology · Apr 2007
Effects of human immunodeficiency virus and methamphetamine on cerebral metabolites measured with magnetic resonance spectroscopy.
Human immunodeficiency virus (HIV) and methamphetamine (METH) use disorders are associated with cerebral dysfunction. To determine whether these effects were evident on in vivo neuroimaging, quantitative, single voxel magnetic resonance (MR) spectroscopy was used to assess frontal white matter, frontal gray matter, and basal ganglia in 40 HIV+/METH+, 66 HIV+/METH-, 48 HIV-/METH+, and 51 HIV-/METH- participants. HIV was associated with lower N-acetylaspartate (NAA) in frontal white and frontal gray matter but METH was not associated with cerebral metabolite differences in any region. ⋯ Although METH was not associated with cerebral metabolite levels, other findings suggested that METH use did affect the brain. For example, the relationship between detectable plasma HIV viral load and NAA levels was limited to HIV+/METH+ individuals. This evidence indicates when HIV is poorly suppressed, METH may modify the effects of the virus on neuronal integrity.
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Journal of neurovirology · Apr 2007
Effects of G207, a conditionally replication-competent oncolytic herpes simplex virus, on the developing mammalian brain.
Viral oncolytic therapy for malignant brain tumors involves local intratumoral delivery of a genetically engineered virus with tumor cell-specific lytic activity. Promising preliminary results have been achieved in preclinical models with G207, a replication-competent herpes simplex virus type 1 constructed with multiple directed mutations. Although the safety of G207 has been demonstrated in adults, application of viral oncolytic therapy to children with brain tumors has been delayed because of previous lack of data concerning the impact of a replication-competent oncolytic virus on the developing mammalian brain. ⋯ However, histological examination and magnetic resonance imaging revealed frequent unilateral ventriculomegaly ipsilateral to the site of injection in only the G207 group. These results suggest that although it is unlikely that G207 will have significant adverse effects on neurodevelopmental outcomes of pediatric patients with brain tumors, an initial study of G207 in children should exclude those patients with tumors in or near the ventricular system as well as patients less than 2 years of age. Furthermore, patients in such a study will need to be closely monitored for the development of hydrocephalus.
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Journal of neurovirology · Aug 2005
Clinical Trial Controlled Clinical TrialImaging glial cell activation with [11C]-R-PK11195 in patients with AIDS.
Glial cell activation occurs in response to brain injury and is present in a wide variety of inflammatory processes including dementia associated with human immunodeficiency virus (HIV). HIV-infected glial cells release cytokines and chemokines that, along with viral neurotoxins, contribute to neuronal damage and apoptosis. The purpose of this study was to determine if glial cell activation in HIV-positive (HIV+) patients could be detected noninvasively, in vivo, using [11C]-R-PK11195 with positron emission tomography (PET). [11C]-R-PK11195 is a selective radioligand for the peripheral benzodiazepine receptor (PBR), and is known to reflect the extent of glial cell activation. ⋯ HIV+ patients overall (demented and nondemented) showed significantly higher radioligand binding than controls in five brain regions (P < 0.05). Patients with HAD did not show significant differences in binding when compared to HIV+ nondemented patients. The findings of this pilot study support a role for glial cell activation in HAD, and that PET with [11C]-R-PK11195 can detect the concomitants of neuronal damage in individuals infected with HIV.