Recovery of mimic function after facial nerve transection is poor. The successful regrowth of regenerating motor nerve fibers to reinnervate their targets is compromised by (i) poor axonal navigation ...and excessive collateral branching, (ii) abnormal exchange of nerve impulses between adjacent regrowing axons, namely axonal crosstalk, and (iii) insufficient synaptic input to the axotomized facial motoneurons. As a result, axotomized motoneurons become hyperexcitable but unable to discharge. We review our findings, which have addressed the poor return of mimic function after facial nerve injuries, by testing the hypothesized detrimental component, and we propose that intensifying the trigeminal sensory input to axotomized and electrophysiologically silent facial motoneurons improves the specificity of the reinnervation of appropriate targets. We compared behavioral, functional, and morphological parameters after single reconstructive surgery of the facial nerve (or its buccal branch) with those obtained after identical facial nerve surgery, but combined with direct or indirect stimulation of the ipsilateral infraorbital nerve. We found that both methods of trigeminal sensory stimulation, i.e., stimulation of the vibrissal hairs and manual stimulation of the whisker pad, were beneficial for the outcome through improvement of the quality of target reinnervation and recovery of vibrissal motor performance.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Microglial cells play an important role in neuroinflammation and secondary damages after spinal cord injury (SCI). Progressive microglia/macrophage inflammation along the entire spinal axis follows ...SCI, and various factors may determine the microglial activation profile. Neurotrophin-3 (NT-3) is known to control the survival of neurons, the function of synapses, and the release of neurotransmitters, while also stimulating axon plasticity and growth. We examined the effects of whole-body vibration (WBV) and forms of assisted locomotor therapy, such as passive flexion-extension (PFE) therapy, at the neuronal level after SCI, with a focus on changes in NT-3 expression and on microglia/macrophage reaction, as they play a major role in the reconstitution of CNS integrity after injury and they may critically account for the observed structural and functional benefits of physical therapy. More specifically, the WBV therapy resulted in the best overall functional recovery when initiated at day 14, while inducing a decrease in Iba1 and the highest increase in NT-3. Therefore, the WBV therapy at the 14th day appeared to be superior to the PFE therapy in terms of recovery. Functional deficits and subsequent rehabilitation depend heavily upon the inflammatory processes occurring caudally to the injury site; thus, we propose that increased expression of NT-3, especially in the dorsal horn, could potentially be the mediator of this favorable outcome.
In this work the development of an autonomous, robust and wearable micro-fluidic platform capable of performing on-line analysis of pH in sweat is discussed. Through the means of an optical detection ...system based on a surface mount light emitting diode (SMD LED) and a light photo sensor as a detector, a wearable system was achieved in which real-time monitoring of sweat pH was performed during 55min of cycling activity. We have shown how through systems engineering, integrating miniaturised electrical components, and by improving the micro-fluidic chip characteristics, the wearability, reliability and performance of the micro-fluidic platform was significantly improved.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Background
Marfan syndrome (MFS) is caused by mutations in the gene encoding fibrillin‐1 (FBN1); however, the mechanisms through which fibrillin‐1 deficiency causes MFS‐associated aortopathy are ...uncertain. Recently, attention was focused on the hypothesis that MFS‐associated aortopathy is caused by increased transforming growth factor‐β (TGF‐β) signaling in aortic medial smooth muscle cells (SMC). However, there are many reasons to doubt that TGF‐β signaling drives MFS‐associated aortopathy. We used a mouse model to test whether SMC TGF‐β signaling is perturbed by a fibrillin‐1 variant that causes MFS and whether blockade of SMC TGF‐β signaling prevents MFS‐associated aortopathy.
Methods and Results
MFS mice (Fbn1C1039G/+ genotype) were genetically modified to allow postnatal SMC‐specific deletion of the type II TGF‐β receptor (TBRII; essential for physiologic TGF‐β signaling). In young MFS mice with and without superimposed deletion of SMC‐TBRII, we measured aortic dimensions, histopathology, activation of aortic SMC TGF‐β signaling pathways, and changes in aortic SMC gene expression. Young Fbn1C1039G/+ mice had ascending aortic dilation and significant disruption of aortic medial architecture. Both aortic dilation and disrupted medial architecture were exacerbated by superimposed deletion of TBRII. TGF‐β signaling was unaltered in aortic SMC of young MFS mice; however, SMC‐specific deletion of TBRII in Fbn1C1039G/+ mice significantly decreased activation of SMC TGF‐β signaling pathways.
Conclusions
In young Fbn1C1039G/+ mice, aortopathy develops in the absence of detectable alterations in SMC TGF‐β signaling. Loss of physiologic SMC TGF‐β signaling exacerbates MFS‐associated aortopathy. Our data support a protective role for SMC TGF‐β signaling during early development of MFS‐associated aortopathy.
BACKGROUND:In unilateral facial palsy, cross-face nerve grafts are used for emotional facial reanimation. Facial nerve regeneration through the grafts takes several months, and the functional results ...are sometimes inadequate. Chronic denervation of the cross-face nerve graft results in incomplete nerve regeneration. The authors hypothesize that donor axons from regional sensory nerves will enhance facial motoneuron regeneration, improve axon regeneration, and improve the amplitude of facial muscle movement.
METHODS:In the rat model, a 30-mm nerve graft (right common peroneal nerve) was used as a cross-face nerve graft. The graft was coapted to the proximal stump of the transected right buccal branch of the facial nerve and the distal stumps of the transected left buccal and marginal mandibular branches. In one group, sensory occipital nerves were coapted end-to-side to the cross-face nerve graft. Regeneration of green fluorescent protein–positive axons was imaged in vivo in transgenic Thy1–green fluorescent protein rats, in which all neurons express green fluorescence. After 16 weeks, retrograde labeling of regenerated neurons and histomorphometric analysis of myelinated axons was performed. Functional outcomes were assessed with video analysis of whisker motion.
RESULTS:“Pathway protection” with sensory axons significantly enhanced motoneuron regeneration, as assessed by retrograde labeling, in vivo fluorescence imaging, and histomorphometry, and significantly improved whisker motion during video analysis.
CONCLUSION:Sensory pathway protection of cross-face nerve grafts counteracts chronic denervation in nerve grafts and improves regeneration and functional outcomes.
Injury to a peripheral nerve induces a complex cellular and molecular response required for successful axon regeneration. Proliferating Schwann cells organize into chains of cells bridging the lesion ...site, which is invaded by macrophages. Approximately half of the injured neuron population sends out axons that enter the glial guidance channels in response to secreted neurotrophic factors and neuropoietic cytokines. These lesion-associated polypeptides create an environment that is highly supportive for axon regrowth, particularly after acute injury, and ensure that the vast majority of regenerating axons are directed toward the distal nerve stump. Unfortunately, most neurotrophic factors and neuropoietic cytokines are also strong stimulators of axonal sprouting. Although some of the axonal branches will withdraw at later stages, the sprouting effect contributes to the misdirection of reinnervation that results in the lack of functional recovery observed in many patients with peripheral nerve injuries. Here, we critically review the role of neuronal growth factors and cytokines during axon regeneration in the peripheral nervous system. Their differential effects on axon elongation and sprouting were elucidated in various studies on intraneuronal signaling mechanisms following nerve lesion. The present data define a goal for future therapeutic strategies, namely, to selectively stimulate a Ras/Raf/ERK-mediated axon elongation program over an intrinsic PI3K-dependent axonal sprouting program in lesioned motor and sensory neurons. Instead of modulating growth factor or cytokine levels at the lesion site, targeting specific intraneuronal molecules, such as the negative feedback inhibitors of ERK signaling, has been shown to promote long-distance regeneration while avoiding sprouting of regenerating axons until they have reached their target areas.
Abstract
Over the last decade, laser surface treatment of stones has gained increasing scientific interest. New technologies and processes based on different types of laser sources and processing ...modes are being studied. This report examines the process of laser ablation of a marble surface using a fiber laser. Three factors influencing the process of laser marking and engraving were studied: laser power, processing speed and step between raster lines. The functional dependencies between these factors and the contrast of the obtained graphic image are established. The optimal operating intervals for this group of technological parameters are analyzed. Thanks to the very-high-definition laser ablation, inscriptions, drawings and images can be re-created and processed with unique accuracy. In addition, the reduction of manufacturing time and resources used in the process makes this technology an environmentally-friendly and extremely cost-efficient solution.
The unique contributions of connexin (Cx)37 and Cx40, gap junction-forming proteins that are coexpressed in vascular endothelium, to the recovery of tissues from ischemic injury are unknown. We ...recently reported that Cx37-deficient (Cx37(-/-)) animals recovered ischemic hindlimb function more quickly and to a greater extent than wild-type (WT) or Cx40(-/-) animals, suggesting that Cx37 limits recovery in the WT animal. Here, we tested the hypothesis that enhanced angiogenesis, arteriogenesis, and vasculogenesis contribute to improved postischemic hindlimb recovery in Cx37(-/-) animals. Ischemia was induced unilaterally in the hindlimbs of WT or Cx37(-/-) mice (isoflurane anesthesia). Postsurgical limb appearance, use, and perfusion were documented during recovery, and the number (and size) of large and small vessels was determined. Native collateral number, predominantly established during embryonic development (vasculogenesis), was also determined in the pial circulation. Both microvascular density in the gastrocnemius of the ischemic limb (an angiogenic field) and the number and tortuosity of larger vessels in the gracilis vasculature (an arteriogenic field) were increased in Cx37(-/-) animals compared with WT animals. Cx37(-/-) mice also had an increased (vs. WT) number of collateral vessels in the pial circulation. These findings suggest that in Cx37(-/-) animals, improved recovery of the ischemic hindlimb involves enhanced vasculogenesis, resulting in increased numbers of collaterals in the hindlimb (and pial circulations) and more extensive collateral remodeling and angiogenesis. These results are consistent with Cx37 exerting a growth-suppressive effect in the vasculature that limits embryonic vasculogenesis as well as arteriogenic and angiogenic responses to ischemic injury in the adult animal.
Highlights • Muscle reinnervation after facial nerve crush (axonotmesis) in rats is precise. • Full functional recovery after crush is not achieved. • Functional deficits are associated with ...deficient synaptic inputs to motoneurons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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