Increased target reinnervation by rescued cervical motoneurons after ventral root avulsion: the effects of spinal cord-brachialis plexus reconnection and riluzole treatment

Although adult motoneurons do not die if their axons are injured at some distance from the cell body, they are vulnerable to injury inflicted on the axons close to the cell body. Ventral root avulsion injury induces death of the vast majority of the affected adult motoneurons. However, some of these cells can be rescued if the avulsed ventral root or a peripheral nerve graft is inserted into the spinal cord. The freshly injured axons of the motoneurons can enter this conduit and are able to grow along the way to the muscles originally innervated by the damaged motoneurons. The neuroprotective effect of riluzole has also been previously proven on the injured motoneurons: they can be rescued even if they have no possibility to regenerate their axons. Here we investigated the strategies that could be used to rescue injured motoneurons and compared their effects. The cervical 7th ventral root (C7) was avulsed and several therapeutic approaches were applied to induce the survival and regeneration of injured motoneurons. Avulsion of the root without reimplantation resulted in very low numbers of surviving motoneurons (65 ± 7.5 SEM), while treatment of the injured motoneurons with riluzole, a potent presynaptic glutamate release inhibitor resulted in significantly higher numbers of surviving motoneurons (637 ± 25.5 SEM). When the C7 ventral root was reimplanted or a peripheral nerve implant was used to guide the regenerating axons to a muscle considerable numbers of motoneurons sent their axons into the vacated endoneural sheaths (211 ± 14.8 SEM and 274 ± 27.8 SEM, respectively). Much greater numbers of axons regenerated when reimplantation was followed by riluzole treatment (573 ± 8.6 SEM). Avulsion and immediate reconnection of the motoneuron pool to the spinal nerve resulted in moderate reinnervation of the spinal nerve (281± 23 SEM retrogradely labelled motoneurons), while treatment of the injured motoneurons with riluzole yielded considerably higher numbers of reinnervating motoneurons (548± 18 SEM). The clinical relevance of our study is given by the brachial plexus injuries that involve the complete or partial avulsion of one or more cervical ventral roots. These injuries can be treated successfully only if satisfactory numbers of motoneurons remain alive following such an injury at the time of reconstructive surgery. In order to that we designed the next step in our study to investigate the capacity of injured motoneurons rescued by riluzole pretreatment to reinnervate denervated forelimb muscles in a model where surgical reconnection with a peripheral nerve graft between the affected spinal cord segment and the C7 spinal nerve was established immediately or with 1 and 3-week-delay after avulsion. Reconnection of the motor pool with the C7 spinal nerve with 1-week-delay allowed fewer motor axons to reinnervate their targets in control and riluzole-treated animals (159± 21 vs 395 ± 16 SEM). A clinically relevant 3-week-delay in reconnection further reduced the number of reinnervating motoneurons (76±22 SEM), but riluzole pretreatment still enabled a significant number of rescued motoneurons (396±17 SEM) to regenerate their axons into the C7 spinal nerve. These results show that adult motoneurons damaged by a brachial plexus injury can be rescued by riluzole treatment even if they cannot regenerate their axons. Reinnervation of the peripheral targets can also be achieved by providing a peripheral conduit for the motoneurons and the extent of reinnervation can be further improved with riluzole treatment. Motoneurons rescued by riluzole are able to reinnervate their targets even if they are provided with a conduit several weeks after the primary injury. This finding suggests that rescuing injured motoneurons with riluzole in patients who suffered a brachial plexus avulsion injury may provide an available pool of surviving motoneurons for late reconnection/reimplantation surgeries

Data Driven: An Autoethnographic Short Story

In this paper, I use an autoethnographic short story (Jago, 2005, 2011) to examine data-driven life in media culture (Kellner, 1995) and the emergence of a quantified self (Wolf, 2010)

Always a Student of Autoethnography

In this paper, I examine the role of a specific place, Minnehaha Falls in Minneapolis, Minnesota, USA, as a particular grounding space on my autoethnographic journey. I assert this grounding space calls me to remember that I am, and will always be, a student of autoethnography

Change in Everyday Life and in the Communication World: A Co-Constructed Performance Autoethnography

In this paper, we use a co-constructed performance autoethnography to explore change in everyday life and in the communication world

A portugál oktatási reformok nemzetközi sikerének háttere

Portugália és Magyarország 2010-es évektől folyó kormányzati oktatásirányítási reformjának időbeli és tartalmi párhuzamrendszere sajátos jelentőséggel bír. A hasonló kondíciókkal rendelkező két ország közül Portugália ezredfordulón mért oktatási teljesítménye a hazainál alacsonyabb színvonalról indulva a 2018-as PISA-mérések időszakára nem csupán Magyarország, de az OECD átlagát is túlszárnyalta. Az elsősorban 2011 és 2015 között bevezetett reformok a magyarországi folyamatoktól, de a nemzetközi szakpolitikai diskurzustól is némileg eltérő példákkal szolgálnak, elsősorban a központi tantervi szabályozás területén

Effects of dietary L -arginine on structure and function of flow-restricted vein grafts

AbstractPurpose: Experiments were designed to determine effects of dietary supplementation with L -arginine on structure and function of flow-restricted vein grafts. Methods: Saphenous veins were placed as bilateral interposition grafts in femoral arteries of two groups of adult male mongrel dogs; one group was maintained on a normal diet (control), the other group supplemented with L -arginine (200 mg/kg per day) beginning 1 week before surgery. In each dog, flow was reduced by 50% in one graft by placing an adjustable clamp on the artery distal to the distal anastomosis. Plasma amino acids and oxidized products of nitric oxide (NOx ) were measured before and after L -arginine feeding. At postoperative week 4, grafts were removed and prepared for organ chamber studies to determine functions of the endothelium or smooth muscle and for histology. Results: Plasma L -arginine increased within 3 hours after feeding and increased from 141 ± 8 nmol/mL to 169 ± 11 nmol/mL (n = 6) after 5 weeks of supplementation. Plasma ornithine and citrulline paralleled arginine, whereas circulating NOx was unchanged. Maximal contractions to 60 mmol/L KCl were reduced in grafts from L -arginine–fed dogs. Endothelium-dependent relaxations to the calcium ionophore A23187 and relaxations of the smooth muscle NO were reduced in grafts from L -arginine–fed dogs. Neointimal hyperplasia was increased in grafts with reduced flow and not affected by arginine feeding. Conclusions: Dietary supplementation with L -arginine did not increase plasma NO in dogs with peripheral vein grafts or increase endothelium-dependent relaxations in control or flow-restricted grafts. Therefore, dietary supplementation with L -arginine may not improve long-term functions of flow-restricted peripheral bypass grafts. (J Vasc Surg 2001;33:829-39.

Urokinase treatment preserves endothelial and smooth muscle function in experimental acute arterial thrombosis

AbstractPurpose: Pharmacologic lysis or balloon thrombectomy are options to treat acute arterial thrombosis; however, little is known about their effects on functional changes in the arterial wall. The aim of this study was to determine function of the endothelium and smooth muscle in canine arteries revascularized after acute thrombosis with balloon thrombectomy or lytic therapy.Methods: Acute thrombosis was obtained by bilateral proximal and distal ligation of 8-cm segments of the femoral arteries in dogs. After 24 hours, the ties were removed and the arteries randomized to treatment groups: group 1, balloon thrombectomy (#4 Fogarty balloon catheter at 60 grams linear shear × 1 pass, n = 7); group 2, untreated, tie removal only (n = 6); group 3, regional intra-arterial urokinase infusion (4000 U/min × 90 min, n = 6); group 4, regional intra-arterial carrier infusion (0.43 ml/min × 90 min, n = 6); group 5, unoperated normal vessels (n = 5). After treatment, the arteries were removed and endothelial and smooth muscle responses examined in organ chambers. Endothelial loss was graded with light microscopy of vessel rings from each animal by an observer blinded to the treatment group. Findings were confirmed with scanning electron microscopy.Results: Treatment with urokinase did not alter endothelium-dependent relaxations or smooth muscle contractions compared with carrier infusion or untreated alone. Balloon catheter thrombectomy significantly reduced endothelium-dependent relaxations compared with all other groups in response to acetylcholine, bradykinin, and thrombin (p < 0.001). Contractions of smooth muscle in response to potassium chloride (60 mol/L) and phenylephrine (1 × 10-6 mol/L) were also reduced (p < 0.05). Rings from balloon thrombectomized arteries contracted in response to calcium ionophore A23187 (p < 0.001); these contractions were endothelium dependent and not reduced by indomethacin or blockade of endothelin A and B receptors. No significant differences in percentage of endothelial coverage between groups were assessed by light and electron microscopy.Conclusion: Thrombolysis with urokinase caused no or minimal abnormalities in endothelial and smooth muscle function. Endothelium present after balloon thrombectomy produces contractile factors. Although the duration and recovery of these abnormalities in function are unknown, these findings support preferential use of urokinase over balloon thrombectomy when possible in acute arterial thrombosis or embolism. (J Vasc Surg 1996;23:851-9.