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Cortical cerebral ischemia elicits neuroinflammation as well as secondary neuronal degeneration in remote areas. Locally distinct and specific secondary neurodegeneration affecting thalamic nuclei connected to cortical areas highlights such processes. Osteopontin (OPN) is a cytokine-like glycoprotein that is excreted in high amounts after cerebral ischemia and exerts various immunomodulatory functions. We here examined putative protective effects of OPN in secondary thalamic degeneration. We subjected male Wistar rats to photothrombosis and subsequently injected OPN or placebo intracerebroventricularly. Immunohistochemical and fluorescence staining was used to detect the extent of neuronal degeneration and microglia activation. Ex vivo autoradiography with radiotracers available for human in vivo PET studies, i.e., cis-4-[18F]Fluor-d-Proline (D-cis-[18F]FPro), and [6-3H]thymidine ([3H]thymidine), confirmed degeneration and proliferation, respectively. We found secondary neurodegeneration in the thalamus characterized by microglial activation and neuronal loss. Neuronal loss was restricted to areas of microglial infiltration. Treatment with OPN significantly decreased neurodegeneration, inflammation and microglial proliferation. Microglia displayed morphological signs of activation without expressing markers of M1 or M2 polarization. D-cis-[18F]FPro-uptake mirrored attenuated degeneration in OPN-treated animals. Notably, [3H]thymidine and BrdU-staining revealed increased stem cell proliferation after treatment with OPN. The data suggest that OPN is able to ameliorate secondary neurodegeneration in thalamic nuclei. These effects can be visualized by radiotracers D-cis-[18F]FPro and [3H]thymidine, opening new vistas for translational studies. [ABSTRACT FROM AUTHOR]

Background: Although it is recognized that carotid endarterectomy (CEA) is the treatment of choice in symptomatic internal carotid artery (ICA) stenosis, in the past, very early CEA has been shown to carry substantial risks. We assessed an interdisciplinary concept of very early CEA in patients with high-grade (>70%) symptomatic ICA stenosis at a single center. Patients and Methods: The course of treatment and outcomes of patients who underwent CEA as early as possible after being referred to the stroke unit for symptoms of transient ischemic attack and stroke were prospectively evaluated, including the following parameters: age, severity of ischemia-related symptoms according to the modified Rankin scale, duration of symptoms until admission, multimodal imaging findings (color-coded duplex, cranial computed tomography, magnetic resonance imaging, positron emission tomography), duration until CEA, perioperative course and complications, as well as duration of in-hospital care. Results: Fifty consecutive patients (median age 68 years, range 44-90) with clinical and imaging signs of transient ischemic attack (n = 19) or stroke (n = 31) were included from January 2000 until December 2004. All except 1 patient showed a preoperative Rankin <4. There was a median time period of 6 h between the onset of symptoms and admission (range 1 h to 15 days) and a median duration of 4 days after admission until operation (range 1-21 days). Seven patients underwent CEA of the contralateral, severely stenosed ICA after symptomatic ipsilateral ICA occlusion. Four out of 5 patients who primarily underwent systemic thrombolysis recovered almost completely. Three patients (6%) experienced a clinical deterioration before surgery. In the majority of patients (43/50), CEA was performed under local anesthesia with selective shunt use which became necessary in 26%. Three patients (6%) had postoperative worsening due to new infarcts. In 2 cases, an intracerebral hemorrhage occurred, of which 1 remained asymptomatic. In 1 case, surgical revision was necessary because of an ICA thrombosis without permanent neurological decline. Patients were discharged after a median time of 14.5 days (range 4-44). Conclusions: After careful selection and preparation in a stroke unit, patients with acute stroke due to carotid stenosis can undergo very early CEA under local anesthesia with a perioperative risk comparable with the risk of later endarterectomy, therefore preventing very early stroke recurrences. [ABSTRACT FROM AUTHOR]

Progressive multifocal leukoencephalopathy is caused by JC virus, an opportunistic infection of the central nervous system. Antiretroviral treatment for progressive multifocal leukoencephalopathy in human immunodeficiency virus-infected patients is beneficial, but few data exist for patients who are not infected with human immunodeficiency virus. Idiopathic CD4+ T lymphocytopenia excludes human immunodeficiency virus infection. We describe a patient with progressive multifocal leukoencephalopathy with underlying idiopathic CD4+ T lymphocytopenia in whom functional recovery occurred without antiviral therapy. [ABSTRACT FROM AUTHOR]

We investigated the variability in infectivity of cells in primary brain tumor samples from different patients using an HSV-1 amplicon vector. We studied the infectivity of HSV-1 amplicon vectors in tumor samples derived from neurosurgical resections of 20 patients. Cells were infected with a definite amount of HSV-1 amplicon vector HSV-GFP. Transduction efficiency in primary tumor cell cultures was compared to an established human glioma line. Moreover, duration of transgene expression was monitored in different tumor cell types. All primary cell cultures were infectable with HSV-GFP with variable transduction efficiencies ranging between 3.0 and 42.4%from reference human Gli36?EGFR glioma cells. Transduction efficiency was significantly greater in anaplastic gliomas and meningiomas (26.7±17.4%) compared to more malignant tumor types (glioblastomas, metastases; 11.2±8.5%; P=0.05). To further investigate the possible underlying mechanism of this variability, nectin-1/HevC expression was analyzed and was found to contribute, at least in part, to this variability in infectability. The tumor cells expressed the exogenous gene for 7 to 61 days with significant shorter expression in glioblastomas (18±13?d) compared to anaplastic gliomas (42±24?d; P<0.05). Interindividual variability of infectivity by HSV-1 virions might explain, at least in part, why some patients enrolled in gene therapy for glioblastoma in the past exhibited a sustained response to HSV-1-based gene- and virus therapy. Infectivity of primary tumor samples from respective patients should be tested to enable the development of efficient and safe herpes vector-based gene and virus therapy for clinical application.Gene Therapy (2005) 12, 588-596. doi:10.1038/sj.gt.3302462 Published online 27 January 2005 [ABSTRACT FROM AUTHOR]