The use of a dual PEDOT and RGD-functionalized alginate hydrogel coating to provide sustained drug delivery and improved cochlear implant function.

Cochlear implants provide hearing by electrically stimulating the auditory nerve. Implant function can be hindered by device design variables, including electrode size and electrode-to-nerve distance, and cochlear environment variables, including the degeneration of the auditory nerve following hair cell loss. We have developed a dual-component cochlear implant coating to improve both the electrical function of the implant and the biological stability of the inner ear, thereby facilitating the long-term perception of sound through a cochlear implant.

Poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings facilitate smaller neural recording electrodes.

We investigated using poly(3,4-ethylenedioxythiophene) (PEDOT) to lower the impedance of small, gold recording electrodes with initial impedances outside of the effective recording range. Smaller electrode sites enable more densely packed arrays, increasing the number of input and output channels to and from the brain. Moreover, smaller electrode sizes promote smaller probe designs; decreasing the dimensions of the implanted probe has been demonstrated to decrease the inherent immune response, a known contributor to the failure of long-term implants.

In vivo electrical conductivity across critical nerve gaps using poly(3,4-ethylenedioxythiophene)-coated neural interfaces.

Background: Bionic limbs require sensitive, durable, and physiologically relevant bidirectional control interfaces. Modern central nervous system interfacing is high risk, low fidelity, and failure prone. Peripheral nervous system interfaces will mitigate this risk and increase fidelity by greatly simplifying signal interpretation and delivery.

Layered carbon nanotube-polyelectrolyte electrodes outperform traditional neural interface materials.

The safety, function, and longevity of implantable neuroprosthetic and cardiostimulating electrodes depend heavily on the electrical properties of the electrode-tissue interface, which in many cases requires substantial improvement. While different variations of carbon nanotube materials have been shown to be suitable for neural excitation, it is critical to evaluate them versus other materials used for bioelectrical interfacing, which have not been done in any study performed so far despite strong interest to this area. In this study, we carried out this evaluation and found that composite multiwalled carbon nanotube-polyelectrolyte (MWNT-PE) multilayer electrodes substantially outperform in one way or the other state-of-the-art neural interface materials available today, namely activated electrochemically deposited iridium oxide (IrOx) and poly(3,4-ethylenedioxythiophene) (PEDOT).

Poly(3,4-ethylenedioxythiophene) as a Micro-Neural Interface Material for Electrostimulation.

Chronic microstimulation-based devices are being investigated to treat conditions such as blindness, deafness, pain, paralysis, and epilepsy. Small-area electrodes are desired to achieve high selectivity. However, a major trade-off with electrode miniaturization is an increase in impedance and charge density requirements.

Electrochemical polymerization of conducting polymers in living neural tissue.

A number of biomedical devices require extended electrical communication with surrounding tissue. Significant improvements in device performance would be achieved if it were possible to maintain communication with target cells despite the reactive, insulating scar tissue that forms at the device-tissue interface. Here, we report that the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) can be polymerized directly within living neural tissue resulting in an electrically conductive network that is integrated within the tissue.

Polymerization of the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) around living neural cells.

In this paper, we describe interactions between neural cells and the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) toward development of electrically conductive biomaterials intended for direct, functional contact with electrically active tissues such as the nervous system, heart, and skeletal muscle. We introduce a process for polymerizing PEDOT around living cells and describe a neural cell-templated conducting polymer coating for microelectrodes and a hybrid conducting polymer-live neural cell electrode. We found that neural cells could be exposed to working concentrations (0.

Minocycline delays disease onset and mortality in reovirus encephalitis.

Minocycline is neuroprotective in many experimental models of neurodegenerative diseases and central nervous system (CNS) injury but has not previously been tested in a model of viral encephalitis. Experimental infection of neonatal mice with neurotropic reoviruses is a classic model for studying the pathogenesis of viral encephalitis. Intracerebral inoculation of serotype 3 reovirus strain Dearing (T3D) in neonatal mice results in lethal encephalitis caused by neuronal apoptosis throughout the CNS.

Nonstructural protein sigma1s is a determinant of reovirus virulence and influences the kinetics and severity of apoptosis induction in the heart and central nervous system.

The mechanisms by which viruses kill susceptible cells in target organs and ultimately produce disease in the infected host remain poorly understood. Dependent upon the site of inoculation and strain of virus, experimental infection of neonatal mice with reoviruses can induce fatal encephalitis or myocarditis. Reovirus-induced apoptosis is a major mechanism of tissue injury, leading to disease development in both the brain and heart.

JNK regulates the release of proapoptotic mitochondrial factors in reovirus-infected cells.

Reovirus-induced apoptosis is associated with activation of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK) and the JNK-associated transcription factor c-Jun. Here we show that reovirus-induced apoptosis and activation of caspase 3 are inhibited in cells deficient in MEK kinase 1, an upstream activator of JNK in reovirus-infected cells. Inhibition of JNK activity following reovirus infection delays the release of proapoptotic mitochondrial factors and the subsequent onset of apoptosis.

Regional differences in viral growth and central nervous system injury correlate with apoptosis.

Infection of neonatal mice with reovirus T3 Dearing (T3D), the prototypic neurotropic reovirus, causes fatal encephalitis associated with neuronal injury and virus-induced apoptosis throughout the brain. T3D variant K (VarK) is an antigenic variant that has a nearly 1 million-fold reduction in neurovirulence following intracerebral (i.c.

Progressive multifocal leukoencephalopathy and apoptosis of infected oligodendrocytes in the central nervous system of patients with and without AIDS.

Context: Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by JC virus (JCV) that occurs in immunocompromised patients. Demyelination of the CNS is a consequence of virus-induced killing of oligodendrocytes, although the exact mechanism of cell death is unknown.

Objective: To examine archival autopsy and surgical pathologic specimens from 8 patients with PML, including 6 patients with human immunodeficiency virus (HIV)-associated PML and 2 patients with non-HIV-associated PML, for evidence of apoptosis.

Reovirus-induced neuronal apoptosis is mediated by caspase 3 and is associated with the activation of death receptors.

Reovirus infection of the central nervous system (CNS) is an important experimental system for understanding the pathogenesis of neurotropic viral infection. Infection of neonatal mice with T3 reoviruses causes lethal encephalitis in which injury results from virus-induced apoptosis. We now show that this apoptosis in vivo is associated with activation of caspase 3, and use neuroblastoma and primary neuronal cultures to identify the cellular pathways involved.