NGF-TrkA Signaling by Sensory Nerves Coordinates the Vascularization and Ossification of Developing Endochondral Bone.

Developing tissues dictate the amount and type of innervation they require by secreting neurotrophins, which promote neuronal survival by activating distinct tyrosine kinase receptors. Here, we show that nerve growth factor (NGF) signaling through neurotrophic tyrosine kinase receptor type 1 (TrkA) directs innervation of the developing mouse femur to promote vascularization and osteoprogenitor lineage progression. At the start of primary ossification, TrkA-positive axons were observed at perichondrial bone surfaces, coincident with NGF expression in cells adjacent to centers of incipient ossification.

Electrical Nerve Stimulation Enhances Perilesional Branching after Nerve Grafting but Fails to Increase Regeneration Speed in a Murine Model.

Background Electrical stimulation immediately following nerve lesion helps regenerating axons cross the subsequently grafted nerve repair site. However, the results and the mechanisms remain open to debate. Some findings show that stimulation after crush injury increases axonal crossing of the repair site without affecting regeneration speed.

MRI of sports-related peripheral nerve injuries.

Objective: Sports-related peripheral nerve injuries are common among athletes and are often underrecognized because of symptom overlap with more usual sports-related bone, soft-tissue, and joint injuries.

Conclusion: MRI plays an increasingly important role in the workup of peripheral nerve injuries and may reveal severe nerve abnormalities before they are diagnosed by electrodiagnostic testing or a clinical examination. Sport-specific peripheral nerve injuries and their MRI appearance will be discussed in this article.

A two-compartment organotypic model of mammalian peripheral nerve repair.

Background: Schwann cells in the distal stump of transected nerve upregulate growth factors that support regeneration on a modality-specific basis. It is unclear, however, which of these preferentially support motor axon regeneration. Identification of these factors will require a model that can isolate growth factor effects to growing axons while reproducing the complex three-dimensional structure of peripheral nerve.

Novel roles for osteopontin and clusterin in peripheral motor and sensory axon regeneration.

Previous studies demonstrated that Schwann cells (SCs) express distinct motor and sensory phenotypes, which impact the ability of these pathways to selectively support regenerating neurons. In the present study, unbiased microarray analysis was used to examine differential gene expression in denervated motor and sensory pathways in rats. Several genes that were significantly upregulated in either denervated sensory or motor pathways were identified and two secreted factors were selected for further analysis: osteopontin (OPN) and clusterin (CLU) which were upregulated in denervated motor and sensory pathways, respectively.

Accelerating axon growth to overcome limitations in functional recovery after peripheral nerve injury.

Objective: Injured peripheral nerves regenerate at very slow rates. Therefore, proximal injury sites such as the brachial plexus still present major challenges, and the outcomes of conventional treatments remain poor. This is in part attributable to a progressive decline in the Schwann cells' ability to provide a supportive milieu for the growth cone to extend and to find the appropriate target.

An in vitro model of adult mammalian nerve repair.

The role of pathway-derived growth factors in the support of peripheral axon regeneration remains elusive. Few appropriate knock-out mice are available, and gene silencing techniques are rarely 100% effective. To overcome these difficulties, we have developed an in vitro organotypic co-culture system that accurately models peripheral nerve repair in the adult mammal.

Electrical stimulation promotes sensory neuron regeneration and growth-associated gene expression.

Brief electrical stimulation enhances the regenerative ability of axotomized motor [Nix, W.A., Hopf, H.

BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair.

Functional recovery after peripheral nerve injury is often poor despite high regenerative capacity of peripheral neurons. In search for novel treatments, brief electrical stimulation of the acutely lesioned nerve has recently been identified as a clinically feasible approach increasing precision of axonal regrowth. The effects of this stimulation appear to be mediated by BDNF and its receptor, TrkB, but the down-stream effectors are unknown.

Peripheral pathways regulate motoneuron collateral dynamics.

Motor axons regenerating after repair of mixed nerve reinnervate pathways leading to muscle more often than those leading to skin [preferential motor reinnervation (PMR)]. Motoneurons that initially project collaterals to both muscle and skin prune incorrect projections to generate specificity. The number of motor axon collaterals maintained entirely within cutaneous or muscle pathways, however, is unknown.

Electrical stimulation restores the specificity of sensory axon regeneration.

Electrical stimulation at the time of nerve repair promotes motoneurons to reinnervate appropriate pathways leading to muscle and stimulates sensory neurons to regenerate. The present experiments examine the effects of electrical stimulation on the specificity of sensory axon regeneration. The unoperated rat femoral cutaneous branch is served by 2-3 times more DRG neurons than is the muscle branch.

Pathway sampling by regenerating peripheral axons.

A century ago, Ramon y Cajal described the generalized response of regenerating peripheral axons to their environment. By using mice that express fluorescent proteins in their axons, we are now able to quantify the response of individual axons to nerve transection and repair. Sciatic nerves from nonexpressing mice were grafted into those expressing a yellow variant of green fluorescent protein, then examined at 5, 7, or 10 days after repair.

Antibodies to myelin-associated glycoprotein accelerate preferential motor reinnervation.

Predegeneration of nerve enhances its ability to support axon regeneration. Trophic factors are upregulated by reactive Schwann cells while potentially inhibitory molecules are removed. These experiments isolate the effects of one such inhibitory molecule, the myelin-associated glycoprotein (MAG), to determine its role in modifying regeneration after nerve repair.

Electrical stimulation promotes motoneuron regeneration without increasing its speed or conditioning the neuron.

Motoneurons reinnervate the distal stump at variable rates after peripheral nerve transection and suture. In the rat femoral nerve model, reinnervation is already substantial 3 weeks after repair, but is not completed for an additional 7 weeks. However, this "staggered regeneration" can be temporally compressed by application of 20 Hz electrical stimulation to the nerve for 1 hr.