Tomáš Kubek

Role of inflammation and cytokines in peripheral nerve regeneration.

This chapter provides a review of immune reactions involved in classic as well as alternative methods of peripheral nerve regeneration, and mainly with a view to understanding their beneficial effects. Axonal degeneration distal to nerve damage triggers a cascade of inflammatory events alongside injured nerve fibers known as Wallerian degeneration (WD). The early inflammatory reactions of WD comprise the complement system, arachidonic acid metabolites, and inflammatory mediators that are related to myelin fragmentation and activation of Schwann cells. Fine-tuned upregulation of the cytokine/chemokine network by Schwann cells activates resident and hematogenous macrophages to complete the clearance of axonal and myelin debris and stimulate regrowth of axonal sprouts. In addition to local effects, immune reactions of neuronal bodies and glial cells are also implicated in the survival and conditioning of neurons to regenerate severed nerves. Understanding of the cellular and molecular interactions between the immune system and peripheral nerve injury opens new possibilities for targeting inflammatory mediators to improve functional reinnervation.

Morphological evidence of collateral sprouting of intact afferent and motor axons of the rat ulnar nerve demonstrated by one type of tracer molecule

In our experimental paradigm we sutured the distal stump of a transected musculocutaneous nerve to an intact ulnar nerve of the rat in an end-to-side fashion. We demonstrated the formation of collateral sprouts from intact afferent and motor axons by application of one type of molecule conjugated by two different fluorophores (Fluoro-Ruby and Fluoro-Emerald). Fluoro-Ruby and Fluoro-Emerald were applied distal to end-to-side suture into fresh cut ends of the ulnar and musculocutaneous nerves, respectively. Formation of collateral sprouts was evidenced by findings of mixed (a yellow to orange color) fluorescence labeling of spinal motoneurons and dorsal root ganglia neurons. Colocalization of two different tracers retrogradely transported to the neurons was verified by the individual green and red fluorescence profiles analyzed by means of the computer-assisted image-analyzing system. Our results unequivocally demonstrate that a nerve stump attached to an intact nerve can induce collateral sprouting of both afferent and motor axons.

Vasospasm of the flap pedicle: the effect of 11 of the most often used vasodilating drugs. Comparative study in a rat model.

Background: There has been no review study published yet comparing the effects of the vasodilating drugs that are most often used in clinical practice empirically. The aim of the authors’ study was to perform this comparison and to select the drugs that are able to release vasospasm and the drugs that reduce vasospasm duration most effectively in an experimental model in vivo. Methods: Pedicled groin flaps were dissected in 300 male Wistar rats. Vasospasm was induced by tension applied on the pedicle in the axial direction using a 15-g weight. The blood perfusion of the flap was monitored using a laser Doppler device. The duration of vasospasm was defined as the time from the release of tension until blood flow began to rise. These times were detected using automated computerized detection. The effects of 11 different drugs were studied in 14 groups. The drugs were applied locally; some of them were tested in different concentrations or applied parenterally. Results: Ten percent magnesium sulfate reduced the duration of vasospasm most effectively (p < 0.01). Verapamil applied locally and also pentoxifylline applied parenterally were also very effective. In contrast, the duration of vasospasm was extended after local application of 2% lidocaine (p < 0.01). Conclusions: The authors concluded that 10% magnesium sulfate applied locally has the best ability to relieve surgically induced vasospasm because of the highest level of significance and reliability. The finding that local application of 2% lidocaine prolongs vasospasm may be surprising.

The proximal first dorsal metacarpal artery free flap for reconstruction of complex digital defects

We describe our experience and outcome with the ‘Proximal first dorsal metacarpal artery free flap’. Ten consecutive cases utilizing the proximal first dorsal metacarpal artery free flap for complex digital defects were studied. Surgical technique, patient demographics, and flap outcome data were collected. Patient satisfaction was analysed using a questionnaire. All defects healed successfully with no loss of free flaps. The short-pedicle proximal first dorsal metacarpal artery free flap enables primary closure of the donor site up to 2 cm of width (in nine of the ten donor sites). The flap is a reliable and versatile alternative in selected cases of complex digital injuries.