Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases

Chronic lung diseases (CLDs) represent a set of disorders characterized by the progressive loss of proper lung function. Among severe CLDs, the incidence of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) has grown over the last decades, mainly in the elderly population. Several studies have highlighted an increased expression of senescence-related markers in the resident progenitor cells in COPD and IPF, possibly undermining epithelial integrity and contributing to the progression and the aggravation of both diseases. Recently, the chronic activation of the canonical Wnt/β-catenin pathway was shown to induce cellular senescence. Here, we investigated the localization and the expression of leucin-rich repeat-containing G-protein-coupled receptor 6 (LGR6), a protein that activates and potentiates the canonical Wnt signalling. Through immunohistochemical analyses, we identified a lesion-associated rise in LGR6 levels in abnormal lung epithelial progenitors in COPD and IPF when compared to histologically normal tissues. Moreover, in areas of aberrant regeneration, chronic damage and fibrosis, LGR6-expressing epithelial progenitors displayed a major increase in the expression of senescence-associated markers. Our study suggests the involvement of LGR6 in the chronic activation of the Wnt/β-catenin pathway, mediating the impairment and exhaustion of epithelial progenitors in COPD and IPF.

A Funhouse Mirror: Muscular Co-Contractions as a Reflection of a Spontaneous Aberrant Regeneration of the Brachial Plexus Injury in the Adults: Anatomical Background, an Attempt to Classify and their Clinical Relevance within the Reconstruction Strategies

A certain number of spontaneously recovering birth injuries to the brachial (BPI) plexus are known to be accompanied by muscle co-contractions (Co-Cs). The process of aberrant spontaneous regeneration contributes to the appearance of this phenomenon. Treatment strategies are mostly narrowed down to temporarily “switching off” the antagonist, allowing the agonist to perform. Less is known about the incidence of BPI-associated Co-Cs in adults (a-BPI), the control of which mainly presumes the extrapolation of a treatment strategy that has been shown to be effective in infants. Nowadays, surgical reconstruction of independent elbow flexion at BPIs relies heavily on redirection (transfer) of nerves that produce their own Co-Cs. These induced Co-Cs could potentially be reduced. Selecting the appropriate nerve transfer strategy (when the donor pool is narrowing), with its potential impact on the already complex and intricate global and segmental biomechanics of the upper extremity, becomes challenging. The chapter presents the anatomical background for the occurrence of muscular Co-Cs, a work on clinical classification of both regeneration associated and induced Co-Cs, possible surgical strategies, their benefits and limitations, in the presence of regeneration-associated muscle Co-Cs at a-BPI and clinical examples.

ABERRANT REGENERATION OF OCULOMOTOR NERVE- LID GAZE DYSKINESIS: A CASE REPORT

Aberrant regeneration of Oculomotor nerve results in the abnormal contraction of the muscles. It occurs because of failure to recover completely after injury to the oculomotor nerve. [1] Here we present a case who presented to us with the signs and symptoms of Aberrant Regeneration of Oculomotor Nerve.

PDGFRα mediated survival of myofibroblasts inhibit satellite cell proliferation during aberrant regeneration of lacerated skeletal muscle

Aberrant regeneration or fibrosis in muscle is the denouement of deregulated cellular and molecular events that alter original tissue architecture due to accumulation of excessive extracellular matrix. The severity of the insult to the skeletal muscle determines the nature of regeneration. Numerous attempts at deciphering the mechanism underlying fibrosis and the subsequent strategies of drug therapies have yielded temporary solutions. Our intent is to understand the interaction between the myofibroblasts (MFs) and the satellite cells (SCs), during skeletal muscle regeneration. We hypothesize that MFs contribute to the impairment of SCs function by exhibiting an antagonistic influence on their proliferation. A modified laceration based skeletal muscle injury model in mouse was utilized to evaluate the dynamics between the SCs and MFs during wound healing. We show that the decline in MFs’ number through inhibition of PDGFRα signaling consequently promotes proliferation of the SCs and exhibits improved skeletal muscle remodeling. We further conclude that in situ administration of PDGFRα inhibitor prior to onset of fibrosis may attenuate aberrant regeneration. This opens new possibility for the early treatment of muscle fibrosis by specific targeting of MFs rather than transplantation of SCs.

Frey's Syndrome

Frey's syndrome is secondary to sympathetic denervation of sweat glands – reinnervation through the auriculotemporal nerve is a secondary event. The aberrant regeneration theory explains the physiopathology of Frey's syndrome. Frey's syndrome incidence after parotidectomy, without prevention techniques, is 40-80% by clinical questioning and 80–100% by objective testing. It occurs months to years after surgery. A topographic and quantitative testing for Frey's is required prior to its treatment – the iodine-sublimated paper histogram (ISPH) test has the majority of desired features. Intradermic botulinum toxin injection is a well-tolerated and efficient treatment. The recommended dilution is 50 IU/1 ml, inter-injection distance is 1 cm, and injection volume is 0.1 ml. Complications to avoid include (1) facial muscle paralysis (rare and reversible complication; inject only intradermally and avoid injecting toward the midline) and (2) pain during injection (if bothersome could be decreased by the prior application of topical anesthetic cream).