Meningothelial Cells React to Elevated Pressure and Oxidative Stress

Xiaorong Xin^1#¤a, Bin Fan^1#¤b, Josef Flammer¹, Neil R. Miller², Gregor P. Jaggi³, Hanspeter E. Killer³, Peter Meyer¹, Albert Neutzner^1*

1 Department of Biomedicine, Ocular Pharmacology and Physiology and Department of Ophthalmology, University Hospital Basel, Basel, Switzerland, 2 Wilmer Ophthalmological Institute, Johns Hopkins Hospital, Baltimore, Maryland, United States of America, 3 Department of Ophthalmology, Kantonsspital Aarau, Aarau, Switzerland

Abstract 

Background

Meningothelial cells (MECs) are the cellular components of the meninges enveloping the brain. Although MECs are not fully understood, several functions of these cells have been described. The presence of desmosomes and tight junctions between MECs hints towards a barrier function protecting the brain. In addition, MECs perform endocytosis and, by the secretion of cytokines, are involved in immunological processes in the brain. However, little is known about the influence of pathological conditions on MEC function; e.g., during diseases associated with elevated intracranial pressure, hypoxia or increased oxidative stress.

Methods

We studied the effect of elevated pressure, hypoxia, and oxidative stress on immortalized human as well as primary porcine MECs. We used MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carbo​ xymethoxyphenyl)-2-(4-sulfophenyl)-2H-te​trazolium)bioreduction assays to assess the proliferation of MECs in response to treatment and compared to untreated control cells. To assess endocytotic activity, the uptake of fluorescently labeled latex beads was analyzed by fluorescence microscopy.

Results

We found that exposure of MECs to elevated pressure caused significant cellular proliferation and a dramatic decrease in endocytotic activity. In addition, mild oxidative stress severely inhibited endocytosis.

Conclusion

Elevated pressure and oxidative stress impact MEC physiology and might therefore influence the microenvironment of the subarachnoid space and thus the cerebrospinal fluid within this compartment with potential negative impact on neuronal function.