Axon Degeneration Is Rescued with Human Umbilical Cord Perivascular Cells: A Potential Candidate for Neuroprotection After Traumatic Brain Injury.

Traumatic brain injury (TBI) leads to delayed secondary injury events consisting of cellular and molecular cascades that exacerbate the initial injury. Human umbilical cord perivascular cells (HUCPVCs) secrete neurotrophic and prosurvival factors. In this study, we examined the effects of HUCPVC in sympathetic axon and cortical axon survival models and sought to determine whether HUCPVC provide axonal survival cues.

Bone-Marrow-Derived Endothelial Progenitor Cell Treatment in a Model of Lateral Fluid Percussion Injury in Rats: Evaluation of Acute and Subacute Outcome Measures.

Traumatic brain injury (TBI) continues to be a serious health care issue while therapies to treat TBI remain elusive. Promising results from the use of endothelial progenitor cells (EPCs) in numerous disease states highlight the pleiotropic capacity of this cell type. We have previously demonstrated that EPC-conditioned media reduces axonal degeneration subsequent to in vitro oxygen-glucose deprivation insult and concurrently improves white matter and microvascular outcome in vivo after mid-line fluid percussion injury.

Bone marrow-derived endothelial progenitor cells protect postischemic axons after traumatic brain injury.

White matter sparing after traumatic brain injury (TBI) is an important predictor of survival and outcome. Blood vessels and axons are intimately associated anatomically and developmentally. Neural input is required for appropriate vascular patterning, and vascular signaling is important for neuron development and axon growth.

p75NTR-dependent, myelin-mediated axonal degeneration regulates neural connectivity in the adult brain.

Axonal degeneration is important during development but has not been thought to function in the intact mature nervous system. Here, we provide evidence that degeneration of adult axons occurs in the intact rodent brain through a p75 neurotrophin receptor (p75NTR)- and myelin-dependent mechanism. Specifically, we show that p75NTR-mediated axonal degeneration prevents septal cholinergic axons from aberrantly growing onto myelinated tracts in vivo or on a myelin substrate in culture.

MECP2 isoform-specific vectors with regulated expression for Rett syndrome gene therapy.

Background: Rett Syndrome (RTT) is an Autism Spectrum Disorder and the leading cause of mental retardation in females. RTT is caused by mutations in the Methyl CpG-Binding Protein-2 (MECP2) gene and has no treatment. Our objective is to develop viral vectors for MECP2 gene transfer into Neural Stem Cells (NSC) and neurons suitable for gene therapy of Rett Syndrome.

Developmental axon pruning mediated by BDNF-p75NTR-dependent axon degeneration.

The mechanisms that regulate the pruning of mammalian axons are just now being elucidated. Here, we describe a mechanism by which, during developmental sympathetic axon competition, winning axons secrete brain-derived neurotrophic factor (BDNF) in an activity-dependent fashion, which binds to the p75 neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, ultimately, axon pruning. Specifically, we found that pruning of rat and mouse sympathetic axons that project to the eye requires both activity-dependent BDNF and p75NTR.

An essential role for the integrin-linked kinase-glycogen synthase kinase-3 beta pathway during dendrite initiation and growth.

Multiple cues, including growth factors and circuit activity, signal to regulate the initiation and growth of mammalian dendrites. In this study, we have asked how these environmental cues regulate dendrite formation, and in particular, whether dendrite initiation and growth requires integrin-linked kinase (ILK) or its downstream effector, glycogen synthase kinase-3beta (GSK-3beta). In cultured sympathetic neurons, NGF and neuronal depolarization activated ILK and promoted dendrite initiation and growth, and inhibition of ILK (either pharmacologically, with a dominant-negative form of ILK, or by genetic knockdown) reduced depolarization-induced dendrite formation.