Generation of periventricular reactive astrocytes overexpressing aquaporin 4 is stimulated by mesenchymal stem cell therapy

Aquaporin-4 (AQP4) plays a crucial role in brain water circulation and is considered a therapeutic target in hydrocephalus. Congenital hydrocephalus is associated with a reaction of astrocytes in the periventricular white matter both in experimental models and human cases. A previous report showed that bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into the lateral ventricles of hyh mice exhibiting severe congenital hydrocephalus are attracted by the periventricular astrocyte reaction, and the cerebral tissue displays recovery. The present investigation aimed to test the effect of BM-MSC treatment on astrocyte reaction formation. BM-MSCs were injected into the lateral ventricles of four-day-old hyh mice, and the periventricular reaction was detected two weeks later. A protein expression analysis of the cerebral tissue differentiated the BM-MSC-treated mice from the controls and revealed effects on neural development. In in vivo and in vitro experiments, BM-MSCs stimulated the generation of periventricular reactive astrocytes overexpressing AQP4 and its regulatory protein kinase D-interacting substrate of 220 kDa (Kidins220). In the cerebral tissue, mRNA overexpression of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1 (HIF1α), and transforming growth factor beta 1 (TGFβ1) could be related to the regulation of the astrocyte reaction and AQP4 expression. In conclusion, BM-MSC treatment in hydrocephalus can stimulate a key developmental process such as the periventricular astrocyte reaction, where AQP4 overexpression could be implicated in tissue recovery

Next generation of ventricular catheters for hydrocephalus based on parametric design

Background The flow pattern of the cerebrospinal fluid is probably the most important factor related to obstruction of ventricular catheters during the normal treatment of hydro cephalus. To better comprehend the flow pattern, we have carried out a parametric study via numerical models of ven tricular catheters. In previous studies, the flow was studied under steady and, recently, in pulsatile boundary conditions by means of computational fluid dynamics (CFD) in three dimensional catheter models. Objective This study aimed to bring in prototype models of catheter CFD flow solutions as well to introduce the theory behind parametric development of ventricular catheters. Methods A preceding study allowed deriving basic principles which lead to designs with improved flow patterns of ventric ular catheters. The parameters chosen were the number of drainage segments, the distances between them, the number and diameter of the holes on each segment, as well as their relative angular position. Results CFD results of previously unreleased models of ven tricular catheter flow solutions are presented in this study. Parametric development guided new designs with better flow distribution while lowering the shear stress of the catheters holes. High-resolution 3D printed catheter solutions of three models and basic benchmark testing are introduced as well. Conclusions The next generation of catheter with homoge neous flow patterns based on parametric designs may repre sent a step forward for the treatment of hydrocephalus, by possibly broadening their lifespan

Effect of surface modification of siliconeon Staphylococcus epidermidis adhesion and colonization

Cerebrospinal fluid (CSF) shunts for the treatment of hydrocephalus are generally made of silicone rubber. The growth of bacterial colonies on the silicone surface leads to frequent CSF shunt complications. A systematic study of the effect of the surface modification of silicone on Staphylococcus epidermidis adhesion and colonization was performed for different incubation times by means of colony counting and scanning electron microscopy (SEM). Silicone was modified with different biopolymers and silanes, including heparin, hyaluronan, octadecyltrichlorosilane (OTS), and fluoroalkylsilane (FAS) to provide a stable and biocompatible surface with different surface functional groups and degrees of hydrophobicity. The modified silicone surfaces were studied by using contact angle measurements, X-ray photoelectron spectroscopy (XPS), and atomic force microscopy (AFM). After 4 and 8 h of incubation, the FAS- and OTS-coated silicone and the hyaluronan coated OTS/silicone surfaces showed significantly reduced bacterial adhesion and colonization compared to blank silicone by both quantification methods. However, the heparin coated OTS/silicone showed significantly increased bacterial adhesion. These results indicate that the nature of the surface functional group and surface roughness determine the extent of bacterial adhesion and colonization. However, the degree of hydrophobicity of the surface did not appear to play a determining role in bacterial adhesion and colonization. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2006Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55980/1/30952_ftp.pd