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Disruption of axonal integrity during injury to the peripheral nerve system (PNS) sets into motion a cascade of responses that includes inflammation, Schwann cell mobilization, and the degeneration of the nerve fibers distal to the injury site. Yet, the injured PNS differentiates itself from the injured central nervous system (CNS) in its remarkable capacity for self-recovery, which, depending upon the length and type of nerve injury, involves a series of molecular events in both the injured neuron and associated Schwann cells that leads to axon regeneration, remyelination repair, and functional restitution. Herein we discuss the essential function of the second messenger, cyclic adenosine monophosphate (cyclic AMP), in the PNS repair process, highlighting the important role the conditioning lesion paradigm has played in understanding the mechanism(s) by which cyclic AMP exerts its proregenerative action. Furthermore, we review the studies that have therapeutically targeted cyclic AMP to enhance endogenous nerve repair.

The development of invasive, rehabilitative neuroprosthetics for humans requires reliable neural probes that are capable of recording large ensembles of neurons for a long period of time. Recent advances in the development of neuroprosthetics in animals and humans have shown that communication and control can be directly derived from the central nervous system (CNS) for restoring lost motor ability [1]. This proof of concept has opened the possibility of new therapies for the millions of individuals suffering from neurological disorders of the nervous system. The success of these therapies hinges on the ability to reliably access the relevant signals from the brain with high quality for the lifetime of the patient. As a result, research has focused on the cascade of events that follow chronic implantation of microelectrodes and temporal degradation in the signal and electrode quality: signal-to-noise ratio, noise floor, peak amplitude, and neuronal yield. Implanted microelectrodes have been reported to suffer from time-dependent degradation in signal quality due to unknown issues related to tissue interfaces.

A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies. The only known negative regulators of cyclic nucleotides are a family of enzymes called phosphodiesterases (PDEs) that hydrolyze cyclic nucleotides into adenosine monophosphate (AMP) or guanylate monophosphate (GMP). Herein, we discuss the structure and physiological function as well as the roles PDEs play in pathological processes of the diseased or injured CNS. Further we review the approaches that have been employed therapeutically in experimental paradigms to block PDE expression or activity and in turn elevate cyclic nucleotide levels to mediate neuroprotection or neurorepair as well as discuss both the translational pathway and current limitations in moving new PDE-targeted therapies to the clinic.

Behavioral hypersensitivity is common following spinal cord injury (SCI), producing significant discomfort and often developing into chronic pain syndromes. While the mechanisms underlying the development of behavioral hypersensitivity after SCI are poorly understood, previous studies of SCI contusion have shown an increase in amino acids, namely, aspartate and glutamate, along with a decrease in GABA and glycine, particularly below the injury. The current study sought to identify alterations in key enzymes and receptors involved in mediating central inhibition via GABA and glycine after a clinically-relevant contusion SCI model. Following thoracic (T8) 25.0 mm NYU contusion SCI in rodents, significant and persistent behavioral hypersensitivity developed as evidenced by cutaneous allodynia and thermal hyperalgesia. Biochemical analyses confirmed upregulation of glutamate receptor GluR3 with downregulation of the GABA synthesizing enzyme (GAD65/67) and the glycine receptor α3 (GLRA3), notably below the injury. Combined, these changes result in the disinhibition of excitatory impulses and contribute to behavioral hyperexcitability. This study demonstrates a loss of central inhibition and the development of behavioral hypersensitivity in a contusive SCI paradigm. Future use of this model will permit the evaluation of different antinociceptive strategies and help in the elucidation of new targets for the treatment of neuropathic pain.

In this work, we develop an experimental testbed that couples biotic and abiotic metrics for studying, quantifying and predicting the effects of chronic electrode implantation on neural electrode performance. The rationale is based on the observation that long-term functionality is the outcome of the interactions between the dynamics of the neuronal environment and the properties of the electrode itself. By combining and analyzing the substantially richer information available in the spatiotemporal dynamics of neurons with biotic and abiotic metrics such as biochemical markers, histochemistry, SEM imaging, and electrochemistry, we seek to quantitatively improve our understanding of the functional modifications underlying the long-term responses of electrode implants. The goal is to ultimately enable the design of future reliable interfaces. In our preliminary analysis using this biotic-abiotic approach of an electrode 18 days post-implant, we observed both structural and histochemical responses related to chronic electrode implantation. These were coupled to daily functional changes in electrode performance. Interestingly, these changes were not correlated with markers of brain injury at the time of electrode explantation. Future work using this multidisciplinary approach is directed to providing a detailed perspective into long-term microelectrode performance.

Ehlers–Danlos syndrome (EDS) type IV is a collagen vascular disease with an autosomal dominant inheritance caused by COL3A1 mutation. Patients with EDS type IV can present with organ rupture, spontaneous arterial dissections and ruptured aneurysms. Because of their propensity to form arterial dissections, aneurysms and rupture, they can develop carotid–cavernous fistula (CCF) after minor trauma or spontaneously. In EDS, it has been reported that even conventional catheter diagnostic angiography may result in large artery dissections and vessel rupture. In addition, the treatment of CCF in EDS type IV can result in up to 59% mortality after initial treatment, of which 23% is attributed to direct complications of treatment. We present the case of a patient with EDS type IV who previously had spontaneous dissection and multiple pseudoaneurysms of both the iliac and femoral arteries and the distal abdominal aorta. Several years later the patient developed a direct type A CCF which was successfully treated with endovascular embolization using a transvenous approach with detachable coils. The literature pertaining to CCF in EDS type IV and its treatment is reviewed.

As the colour palette of solution processable electrochromic conjugated polymers has extended from hues of purple and blue to vibrant colours such as yellow, orange, red, green, and cyan, the need for a counter electrode material that provides charge balance in electrochromic devices, but lends minimal colour, has become increasingly necessary. Nowhere is this more true than in absorptive/transmissive window-type devices where a high level of transparency and near colourlessness is needed in the device bleached state. This argument can also be extended to absorptive/reflective display-type devices where an “on” (coloured) and “off” (bleached or white) state is desired. Here, we report the development of a highly electroactive, low colouration efficiency propylenedioxypyrrole-based polymer that exhibits a low redox potential and minimal colour saturation in both fully neutralised and fully oxidised states. Thin films of the polymer, spray-cast onto transparent electrodes exhibited relatively low composite colouration efficiencies at 555 nm of 35 cm2C−1, contrasted with the the high colouration efficiency ECP-Magenta that exhibits 633 cm2C−1. We further demonstrate the utilisation of this polymer as an effective charge balancing counter electrode material in an absorptive/transmissive window-type device wherein the vibrantly coloured state and highly transmissive, near colourless bleached state of ECP-Magenta is maintained giving an overall device contrast of 61% at 540 nm.