A Model of Free Tissue Transfer: The Rat Epigastric Free Flap

Free tissue transfer has been increasingly used in clinical practice since the 1970s, allowing reconstruction of complex and otherwise untreatable defects ...

Functional and Physiological Methods of Evaluating Median Nerve Regeneration in the Rat

The main goal of this investigation is to show how to create and repair different types of median nerve (MN) lesions in the rat. Moreover, different ...

Universidade Nova de Lisboa

Nova Medical School

Zebrafish are able to regenerate many of its tissues and organs after damage. In amphibians this process is regulated by nerve fibres present at the site of injury, which have been proposed to release factors into the amputated limbs/fins, promoting and sustaining the proliferation of blastemal cells. Although some candidate factors have been proposed to mediate the nerve dependency of regeneration, the molecular mechanisms involved in this process remain unclear.

Denervation impairs regeneration of amputated zebrafish fins.

Caudal fin regeneration is characterized by a proliferation boost in the mesenchymal blastema that is controlled precisely in time and space. This allows a gradual and robust restoration of original fin size. However, how this is established and regulated is not well understood. Here, we report that Yap, the Hippo pathway effector, is a chief player in this process: functionally manipulating Yap during regeneration dramatically affects cell proliferation and expression of key signaling pathways, impacting regenerative growth. The intracellular location of Yap is tightly associated with different cell densities along the blastema proximal-distal axis, which correlate with alterations in cell morphology, cytoskeleton and cell-cell contacts in a gradient-like manner. Importantly, Yap inactivation occurs in high cell density areas, conditional to F-actin distribution and polymerization. We propose that Yap is essential for fin regeneration and that its function is dependent on mechanical tension, conferred by a balancing act of cell density and cytoskeleton activity.

Control of tissue growth by Yap relies on cell density and F-actin in zebrafish fin regeneration.

The aim of this study was to evaluate in the Wistar rat the efficacy of various autologous nerve conduits with various forms of blood supply in reconstructing a 10-mm-long gap in the median nerve (MN) under conditions of local ischemia. A 10-mm-long median nerve defect was created in the right arm. A loose silicone tube was placed around the nerve gap zone, in order to simulate a local ischemic environment. Rats were divided in the following experimental groups (each with 20 rats): the nerve Graft (NG) group, in which the excised MN segment was reattached; the conventional nerve flap (CNF) and the arterialized neurovenous flap (ANVF) groups in which the gap was bridged with homonymous median nerve flaps; the prefabricated nerve flap (PNF) group in which the gap was reconstructed with a fabricated flap created by leaving an arteriovenous fistula in contact with the sciatic nerve for 5 weeks; and the two control groups, Sham and Excision groups. In the latter group, the proximal stump of the MN nerve was ligated and no repair was performed. The rats were followed for 100 days. During this time, they did physiotherapy. Functional, electroneuromyographic and histological studies were performed. The CNF and ANVF groups presented better results than the NG group in the following assessments: grasping test, nociception, motor stimulation threshold, muscle weight, and histomorphometric evaluation. Radial deviation of the operated forepaw was more common in rats that presented worse results in the other outcome variables. Overall, CNFs and ANVFs produced a faster and more complete recovery than NGs in the reconstruction of a 10-mm-long median nerve gap in an ischemic environment in the Wistar rat. Although, results obtained with CNFs were in most cases were better than ANVFs, these differences were not statistically significant for most of the outcome variables.

Reconstruction of a 10-mm-long median nerve gap in an ischemic environment using autologous conduits with different patterns of blood supply: A comparative study in the rat.

Axon ensheathment is fundamental for fast impulse conduction and the normal physiological functioning of the nervous system. Defects in axonal insulation lead to debilitating conditions, but, despite its importance, the molecular players responsible are poorly defined. Here, we identify RalA GTPase as a key player in axon ensheathment in  larval peripheral nerves. We demonstrate through genetic analysis that RalA action through the exocyst complex is required in wrapping glial cells to regulate their growth and development. We suggest that the RalA-exocyst pathway controls the targeting of secretory vesicles for membrane growth or for the secretion of a wrapping glia-derived factor that itself regulates growth. In summary, our findings provide a new molecular understanding of the process by which axons are ensheathed , a process that is crucial for normal neuronal function.

Ana Farinho

CEDOC,
NOVA Medical School,
CEDOC, NOVA Medical School

Universidade Nova de Lisboa

A Model of Free Tissue Transfer: The Rat Epigastric Free Flap

Functional and Physiological Methods of Evaluating Median Nerve Regeneration in the Rat

Ana Farinho

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Universidade Nova de Lisboa

A Model of Free Tissue Transfer: The Rat Epigastric Free Flap

Functional and Physiological Methods of Evaluating Median Nerve Regeneration in the Rat

CEDOC,
NOVA Medical School,
CEDOC, NOVA Medical School