Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trial.

Background: Spinal cord injury (SCI) causes neural disconnection and persistent neurological deficits, so axon sprouting and plasticity might promote recovery. Soluble Nogo-Receptor-Fc decoy (AXER-204) blocks inhibitors of axon growth and promotes recovery of motor function after SCI in animals. This first-in-human and randomised trial sought to determine primarily the safety and pharmacokinetics of AXER-204 in individuals with chronic SCI, and secondarily its effect on recovery.

Delayed intrathecal delivery of RhoA siRNA to the contused spinal cord inhibits allodynia, preserves white matter, and increases serotonergic fiber growth.

RhoA is a key regulator of the actin cytoskeleton that is upregulated after spinal cord injury (SCI). We analyzed different methods for siRNA delivery and developed siRNAs targeting RhoA (siRhoA) for SCI treatment. Cy 3.

Enhancement of endocannabinoid signaling by fatty acid amide hydrolase inhibition: a neuroprotective therapeutic modality.

Aims: This review posits that fatty acid amide hydrolase (FAAH) inhibition has therapeutic potential against neuropathological states including traumatic brain injury; Alzheimer's, Huntington's, and Parkinson's diseases; and stroke.

Main Methods: This proposition is supported by data from numerous in vitro and in vivo experiments establishing metabolic and pharmacological contexts for the neuroprotective role of the endogenous cannabinoid ("endocannabinoid") system and selective FAAH inhibitors.

Key Findings: The systems biology of endocannabinoid signaling involves two main cannabinoid receptors, the principal endocannabinoid lipid mediators N-arachidonoylethanolamine ("anandamide") (AEA) and 2-arachidonoyl glycerol (2-AG), related metabolites, and the proteins involved in endocannabinoid biosynthesis, biotransformation, and transit.

The mammalian exocyst, a complex required for exocytosis, inhibits tubulin polymerization.

The exocyst is a 734-kDa complex essential for development. Perturbation of its function results in early embryonic lethality. Extensive investigation has revealed that this complex participates in multiple biological processes, including protein synthesis and vesicle/protein targeting to the plasma membrane.

Dendrotoxin-sensitive K(+) currents contribute to accommodation in murine spiral ganglion neurons.

We have previously identified two broad electrophysiological classes of spiral ganglion neuron that differ in their rate of accommodation (Mo & Davis, 1997a). In order to understand the underlying ionic basis of these characteristic firing patterns, we used alpha-dendrotoxin (alpha-DTX) to eliminate the contribution of a class of voltage-gated K(+) channels and assessed its effects on a variety of electrophysiological properties by using the whole-cell configuration of the patch-clamp technique. Exposure to alpha-DTX caused neurons that initially displayed rapid accommodation to fire continuously during 240 ms depolarizing test pulses within a restricted voltage range.

Firing features and potassium channel content of murine spiral ganglion neurons vary with cochlear location.

Neurons from varied regions of the central nervous system can show widely divergent responses to electrical stimuli that are determined by cell-specific differences in ion channel composition. The well-ordered and highly characterized peripheral auditory system allows one to explore the significance of this diversity during the final stages of postnatal development. We examined the electrophysiological features of murine spiral ganglion neurons in vitro at a time when recordings could be made from the cell bodies before myelination.

Opposite actions of brain-derived neurotrophic factor and neurotrophin-3 on firing features and ion channel composition of murine spiral ganglion neurons.

It is now well established that sensory neurons and receptors display characteristic morphological and electrophysiological properties tailored to their functions. This is especially evident in the auditory system, where cells are arranged tonotopically and are highly specialized for precise coding of frequency- and timing-dependent auditory information. Less well understood, however, are the mechanisms that give rise to these biophysical properties.