Photograftable Zwitterionic Coatings Prevent and Adhesion to PDMS Surfaces.

Due to its attractive mechanical properties and biocompatibility, poly(dimethyl)siloxane (PDMS) is widely used in the fabrication of biomedical materials. On the other hand, PDMS is also prone to adsorption of both proteins and bacteria, making PDMS implants susceptible to infection. Herein, we examine the use of durably cross-linked zwitterionic coatings for PDMS surfaces to mitigate bacterial adhesion.

Antifouling Photograftable Zwitterionic Coatings on PDMS Substrates.

The foreign body response (FBR) to implantable materials can negatively impact performance of medical devices such as the cochlear implant. Engineering surfaces that resist the FBR could lead to enhanced functionality including potentially improving outcomes for cochlear implant recipients through reduction in fibrosis. In this work, we coat poly(dimethylsiloxane) (PDMS) surfaces with two zwitterionic polymers, poly(sulfobetaine methacrylate) (pSBMA) and poly(carboxybetaine methacrylate) (pCBMA), using a simultaneous photografting/photo-cross-linking process to produce a robust grafted zwitterionic hydrogel.

Photopolymerizable Zwitterionic Polymer Patterns Control Cell Adhesion and Guide Neural Growth.

Developing materials that reduce or eliminate fibrosis encapsulation of neural prosthetic implants could significantly enhance implant fidelity by improving the tissue/electrode array interface. Here, we report on the photografting and patterning of two zwitterionic materials, sulfobetaine methacrylate (SBMA) and carboxybetaine methacrylate (CBMA), for controlling the adhesion and directionality of cells relevant to neural prosthetics. CBMA and SBMA polymers were photopolymerized and grafted on glass surfaces then characterized by X-ray photoelectron spectroscopy, water contact angle, and protein adsorption.

Quantifying Spiral Ganglion Neurite and Schwann Behavior on Micropatterned Polymer Substrates.

The first successful in vitro experiments on the cochlea were conducted in 1928 by Honor Fell (Fell, Arch Exp Zellforsch 7(1):69-81, 1928). Since then, techniques for culture of this tissue have been refined, and dissociated primary culture of the spiral ganglion has become a widely accepted in vitro model for studying nerve damage and regeneration in the cochlea. Additionally, patterned substrates have been developed that facilitate and direct neural outgrowth.

Cortical glial fibrillary acidic protein-positive cells generate neurons after perinatal hypoxic injury.

Glial fibrillary acidic protein-positive (GFAP(+)) cells give rise to new neurons in the neurogenic niches; whether they are able to generate neurons in the cortical parenchyma is not known. Here, we use genetic fate mapping to examine the progeny of GFAP(+) cells after postnatal hypoxia, a model for the brain injury observed in premature children. After hypoxia, immature cortical astroglia underwent a shift toward neuronal fate and generated cortical excitatory neurons that appeared synaptically integrated into the circuitry.

Precursors with glial fibrillary acidic protein promoter activity transiently generate GABA interneurons in the postnatal cerebellum.

Neural stem or progenitor cells (NSC/NPCs) able to generate the different neuron and glial cell types of the cerebellum have been isolated in vitro, but their identity and location in the intact cerebellum are unclear. Here, we use inducible Cre recombination in GFAPCreER(T2) mice to irreversibly activate reporter gene expression at P2 (postnatal day 2), P5, and P12 in cells with GFAP (glial fibrillary acidic protein) promoter activity and analyze the fate of genetically tagged cells in vivo. We show that cells tagged at P2-P5 with beta-galactosidase or enhanced green fluorescent proteins reporter genes generate at least 30% of basket and stellate GABAergic interneurons in the molecular layer (ML) and that they lose their neurogenic potential by P12, after which they generate only glia.

Fgfr1 is required for cortical regeneration and repair after perinatal hypoxia.

Chronic postnatal hypoxia causes an apparent loss of cortical neurons that is reversed during recovery (Fagel et al., 2006). The cellular and molecular mechanisms underlying this plasticity are not understood.

Marked differences in the efficacy of post-insult gene therapy with catalase versus glutathione peroxidase.

It is now recognized that the generation of reactive oxygen species (ROS) following necrotic neurological insults plays a central role in the subsequent neuron death. A key step in ROS detoxification is the conversion of hydrogen peroxide to water and oxygen by either catalase (CAT) or glutathione peroxidase (GPX). We have previously shown that overexpression of CAT or GPX protects cultured neurons against subsequent excitotoxic insults.

Dual-gene, dual-cell type therapy against an excitotoxic insult by bolstering neuroenergetics.

Increasing evidence suggests that glutamate activates the generation of lactate from glucose in astrocytes; this lactate is shuttled to neurons that use it as a preferential energy source. We explore this multicellular "lactate shuttle" with a novel dual-cell, dual-gene therapy approach and determine the neuroprotective potential of enhancing this shuttle. Viral vector-driven overexpression of a glucose transporter in glia enhanced glucose uptake, lactate efflux, and the glial capacity to protect neurons from excitotoxicity.

Over-expression of antioxidant enzymes protects cultured hippocampal and cortical neurons from necrotic insults.

There is now considerable knowledge concerning neuron death following necrotic insults, and it is believed that the generation of reactive oxygen species (ROS) and oxidative damage play a pivotal role in the neuron death. Prompted by this, we have generated herpes simplex virus-1 amplicon vectors over-expressing the genes for the antioxidant enzymes catalase (CAT) or glutathione peroxidase (GPX), both of which catalyze the degradation of hydrogen peroxide. Over-expression of each of these genes in primary hippocampal or cortical cultures resulted in increased enzymatic activity of the cognate protein.

Neuroprotective effects of bcl-2 overexpression in hippocampal cultures: interactions with pathways of oxidative damage.

Overexpression of bcl-2protects neurons from numerous necrotic insults, both in vitro and in vivo. While the bulk of such protection is thought to arise from Bcl-2 blocking cytochrome c release from mitochondria, thereby blocking apoptosis, the protein can target other steps in apoptosis, and can protect against necrotic cell death as well. There is evidence that these additional actions may be antioxidant in nature, in that Bcl-2 has been reported to protect against generators of reactive oxygen species (ROS), to increase antioxidant defenses and to decrease levels of ROS and of oxidative damage.