Evidence for a systemic regulation of neurotrophin synthesis in response to peripheral nerve injury.

Up-regulation of neurotrophin synthesis is an important mechanism of peripheral nerve regeneration after injury. Neurotrophin expression is regulated by a complex series of events including cell interactions and multiple molecular stimuli. We have studied neurotrophin synthesis at 2 weeks time-point in a transvertebral model of unilateral or bilateral transection of sciatic nerve in rats.

Accelerated axon outgrowth, guidance, and target reinnervation across nerve transection gaps following a brief electrical stimulation paradigm.

Object: Regeneration of peripheral nerves is remarkably restrained across transection injuries, limiting recovery of function. Strategies to reverse this common and unfortunate outcome are limited. Remarkably, however, new evidence suggests that a brief extracellular electrical stimulation (ES), delivered at the time of injury, improves the regrowth of motor and sensory axons.

A long peripheral nerve autograft model in the sheep forelimb.

Background: Autologous nerve grafts remain the only proven means of bridging lengthy gaps in peripheral nerve. However, there is very little literature on a reliable long (> 5 cm) nerve autograft animal model.

Objective: To establish a reproducible long nerve gap and autograft animal model that is clinically relevant but not cost prohibitive.

The microvascular impact of focal nerve trunk injury.

The microvascular supply of the peripheral nerve trunk may be rendered vulnerable by acute focal injuries, particularly if they are associated with direct injury to the epineurial blood supply. In this work we tracked the impact of three clinically relevant forms of focal nerve trunk injury on serial measures of epineurial weighted erythrocyte flux and endoneurial blood flow: short-length crush injuries, long-segmental crush injuries, and crush injuries with superimposed vascular stripping to model added direct epineurial damage. Red blood cell (RBC) flux was measured using quantitative multiple sampling laser doppler flowmetry, and endoneurial blood flow by microelectrode hydrogen clearance polarography.

Motoneuron survival after chronic and sequential peripheral nerve injuries in the rat.

Object: Surgical repair of peripheral nerves following chronic nerve injury is associated with poor axonal regeneration and outcome. An underlying possibility is that chronic injuries may increase motoneuron cell death. The hypothesis that substantial motoneuron death follows chronic and sequential nerve injuries was tested in adult rats in this study.

Prolonged target deprivation reduces the capacity of injured motoneurons to regenerate.

Objective: To investigate whether or not it is the frustrated growth state (no axon growth) that reduces regenerative capacity or the inability of axotomized motoneurons to remake muscle connections (axon growth-no muscle contact) that accounts for poor regenerative capacity of chronically axotomized motoneurons.

Methods: We chronically axotomized rat femoral motoneurons for 2 months by cutting the nerve and either capping the proximal nerve to prevent axon regeneration (Group 1, no axon growth for 2 mo) or encouraging axon regeneration but not target reinnervation by suture to the distal stump of cut saphenous nerve (Group 2, axon growth with no muscle contact). In the control fresh axotomy group (axon growth with muscle contact), femoral nerve stumps were resutured immediately.

Regeneration into protected and chronically denervated peripheral nerve stumps.

Objective: Delayed repair of peripheral nerve injuries often results in poor motor functional recovery. This may be a result of the deterioration or loss of endoneurial pathways in the distal nerve stump before motor axons can regenerate into the stump.

Methods: Using the rat femoral nerve, we protected distal endoneurial pathways of the saphenous nerve with either cross-suture of the quadriceps motor nerve (Group A) or resuture of the saphenous nerve (Group B) to compare later motor regeneration into the "protected" saphenous nerve pathway to chronic denervation and "unprotected" saphenous nerve (Group C).

Histological and magnetic resonance analysis of sciatic nerves in the tellurium model of neuropathy.

Ingestion of tellurium (Te), a toxic element, produces paralysis of the hind limbs in weanling rats that is due to temporary, segmental demyelination of the sciatic nerves bilaterally. Weanling rats were fed a 1.1% elemental Te diet and sacrificed at various time points for histological and magnetic resonance (MR) analysis of the sciatic nerves.

Mu opioid receptors and analgesia at the site of a peripheral nerve injury.

Opioid ligands may exert antinociception through receptors expressed on peripheral afferent axons. Whether local opioid receptors might attenuate neuropathic pain is uncertain. In this work, we examined the function and expression of local mu opioid receptors (MORs) associated with the chronic constriction injury (CCI) model of sciatic neuropathic pain in rats.

Ischemia and failed regeneration in chronic experimental neuromas.

Neuromas are generally considered to be swollen uniform collections of uncontrolled aberrantly sprouting axons. In early experimental neuromas, there are substantial rises in local blood flow associated with their formation, but human studies of chronic lesions have suggested that neuromas develop ischemia and become impediments to regeneration. The issue is important because traumatically severed human nerves are frequently considered for repair some time after injury, when neuroma formation has occurred.