CSF from Parkinson disease patients differentially affects cultured microglia and astrocytes.

BACKGROUND: Excessive and abnormal accumulation of alpha-synuclein (α-synuclein) is a factor contributing to pathogenic cell death in Parkinson's disease. The purpose of this study, based on earlier observations of Parkinson's disease cerebrospinal fluid (PD-CSF) initiated cell death, was to determine the effects of CSF from PD patients on the functionally different microglia and astrocyte glial cell lines. Microglia cells from human glioblastoma and astrocytes from fetal brain tissue were cultured, grown to confluence, treated with fixed concentrations of PD-CSF, non-PD disease control CSF, or control no-CSF medium, then photographed and fluorescently probed for α-synuclein content by deconvolution fluorescence microscopy. Outcome measures included manually counted cell growth patterns from day 1-8; α-synuclein density and distribution by antibody tagged 3D model stacked deconvoluted fluorescent imaging. RESULTS: After PD-CSF treatment, microglia growth was reduced extensively, and a non-confluent pattern with morphological changes developed, that was not evident in disease control CSF and no-CSF treated cultures. Astrocyte growth rates were similarly reduced by exposure to PD-CSF, but morphological changes were not consistently noted. PD-CSF treated microglia showed a significant increase in α-synuclein content by day 4 compared to other treatments (p ≤ 0.02). In microglia only, α-synuclein aggregated and redistributed to peri-nuclear locations. CONCLUSIONS: Cultured microglia and astrocytes are differentially affected by PD-CSF exposure compared to non-PD-CSF controls. PD-CSF dramatically impacts microglia cell growth, morphology, and α-synuclein deposition compared to astrocytes, supporting the hypothesis of cell specific susceptibility to PD-CSF toxicity.

Use of intrathecal urokinase in repeated shunt and external ventricular drain blockage from high CSF protein due to an optic pathway glioma.

INTRODUCTION: High cerebrospinal fluid (CSF) protein is a recognised association of optic pathway gliomas. This can occlude ventriculoperitoneal (VP) shunt catheters or external ventricular drains (EVD). CASE REPORT: We describe an 8-year-old boy with an optic pathway glioma, who had frequent episodes of a blocked VP shunt and EVD due to high CSF protein level. This responded favourably to repeated urokinase instillation into the catheter lumen. We present the course of treatment and the method of administration and review the literature behind thrombolytic therapy for occluded catheter devices. CONCLUSION: Intrathecal urokinase was effective in unblocking the EVD and lysing the protein clots within the ventricle. We found no previously published cases of intrathecal urokinase for this problem. This novel intervention seemed promising as a safe and effective means of maintaining EVD patency in cases complicated by excessive protein loads in CSF and hydrocephalus.

[Effect of protein-containing cerebrospinal fluid on ventriculo-auricular drainage]. / Zum Einfluss von eiweisshaltigem Liquor auf ventrikulo-aurikuläre Drainagen.

Elevated protein level in liquor still prohibits ventriculo-auricular drainage methods. Spitz-Holter valves and Pudenz-Heyer valves were therefore tried in model tests using plasma-containing fluids. The quantities of flow depending on time were presented on graphs. A considerably reduced flow through the Spitz-Holter valve was observed after brief perfusion already, with tendency to complete occlusion. Similar results were obtained from trials on the Pudenz-Heyer valve.