Enhancing regenerative potential: A comprehensive review of stem cell transplantation for sports-related neuronal injuries, with a focus on spinal cord injuries and peripheral nervous system damage.

Neuronal injuries, as one of the consequences of sports-related incidents, exert a profound influence on the athletes' future, potentially leading to complete immobility and impeding their athletic pursuits. In cases of severe damage inflicted upon the spinal cord (SC) and peripheral nervous systems (PNS), the regenerative process is notably compromised, rendering it essentially inefficient. Among the pivotal therapeutic approaches for the enhancement and prevention of secondary SC injuries (SCI), stem cell transplantation (SCT) stands out prominently. Stem cells, whether directly involved in replacement and reconstruction or indirectly through modification and secretion of crucial bioenvironmental factors, engage in the intricate process of tissue regeneration. Stem cells, through the secretion of neurotrophic factors (NTFs) (aiming to modulate the immune system), reduction of inflammation, axonal growth stimulation, and myelin formation, endeavor to facilitate the regeneration of damaged SC tissue. The fundamental challenges of this approach encompass the proper selection of suitable stem cell candidates for transplantation and the establishment of an appropriate microenvironment conducive to SC repair. In this article, an attempt has been made to explore sports-related injuries, particularly SCI, to comprehensively review innovative methods for treating SCI, and to address the existing challenges. Additionally, some of the stem cells used in neural injuries and the process of their utilization have been discussed.

Aplicación y seguimiento del tratamiento del dolor neuropático periférico con capsaicina 179 mg realizado por enfermeras / Application and follow-up of the peripheral neuropathic pain treatment with capsaicin 179 mg conducted by nurses

Objetivo: evaluar la efectividad del tratamiento con parches de capsaicina 179 mg en personas con dolor neuropático periférico aplicado y en seguimiento realizado por enfermeras. Método: serie de casos longitudinal retrospectiva efectuada en la Unidad de Dolor del Hospital Universitario Son Llàtzer (Palma) entre 2018 y 2020. La población de estudio fue de 163 personas con ese tratamiento. Se llevó a cabo medición basal al mes, a los tres y a los seis meses. Se midieron sexo, edad, tiempo de evolución, aplicaciones realizadas, mejora en intensidad (NPRS: 0 a 10 puntos) y extensión del dolor, calidad de vida relacionada con la salud (EQ-5D-3L: 0 peor a 1 mejor), impresión de mejoría global del paciente (PGI-I: mejora; empeora o no mejora), uso de fármacos adyuvantes y efectos secundarios. Se llevó a cabo estadística descriptiva. Resultados: se incluyeron 133 pacientes con registros completos (= 57 años; = 30,2 meses de evolución; = 1,6 aplicaciones por persona). Se redujo la zona de dolor [Sí reduce (Mes 1: 67%; Mes 3: 41%; Mes 6: 20%)] y la intensidad del dolor pasó de = 7,35 a 6,32 al sexto mes. La calidad de vida fue superior a la media basal (0,37 sobre 1) en todas las mediciones. Mejoró la PGI [Mejora (Mes 1: 64,6%: Mes 3: 58,9%; Mes 6: 53,6 %)]. Disminuyó el uso de medicación adyuvante [Sí reduce (Mes 1: 28%; Mes 3: 30%; Mes 6: 67%)]. Los efectos adversos fueron dolor (78,9%), eritema (67,7%) y prurito (63,9%). Conclusión: el tratamiento aplicado por enfermeras fue eficaz y seguro. El seguimiento debe ser prolongado para detectar necesidades y cambios.(AU)

Objective: to evaluate the efficacy of the treatment with capsaicin 179mg patches applied and on follow-up by nurses in persons with peripheral neuropathic pain. Method: a longitudinal retrospective series of cases conducted at the Pain Unit of the Hospital Universitario Son Llàtzer between 2018 and 2020. The study population consisted of 196 persons with that treatment. Basal measurement was conducted at one month, at three and six months. The following were measured: gender, age, time of evolution, applications conducted, improvement in intensity (NPRS scale: 0 to 10 points) and extent of pain, health-related quality of life (EQ-5D-3L: 0=the worst to 1=the best), patient global impression of improvement (PGI-I: improvement, worsening or no improvement), use of adjuvant drugs and side effects. Descriptive statistics was applied. Results: 133 patients were included with complete records(= 57 years; = 30.2 months of evolution; = 1.6 applications per person). There was a reduction in the pain area [Reduced (Month 1: 67%; Month 3: 41%; Month 6: 20%)] and pain intensity moved from = 7.35 to 6.32 at month six. Quality of life was superior to the mean baseline (0.37 of 1) in all measurements. There was improvement in PGI [Improvement (Month 1: 64.6%: Month 3: 58.9%; Month 6: 53.6 %)]. There was a reduction in the use of adjuvant medication [Reduced (Month 1: 28%; Month 3: 30%; Month 6: 67%)]. The adverse effects were pain (78.9%), erythema (67.7%) and itching (63.9%). Conclusion: the treatment applied by nurses was effective and safe. There must be follow-up at long term in order to detect any needs and changes.(AU)

Traumatic Injuries to the Spinal Cord and Peripheral Nervous System.

Both blunt and penetrating trauma can cause injuries to the peripheral and central nervous systems. Emergency providers must maintain a high index of suspicion, especially in the setting of polytrauma. There are 2 major classifications of peripheral nerve injuries (PNIs). Some PNIs are classically associated with certain traumatic mechanisms. Most closed PNIs are managed conservatively, whereas sharp nerve transections require specialist consultation for urgent repair. Spinal cord injuries almost universally require computed tomography imaging; some require emergent magnetic resonance imaging. Providers should work to minimize secondary injury. Surgical specialists are needed for closed reduction, surgical decompression, or stabilization.

Spectral Characterization of Stem Cell-Derived Myelination within the Injured Adult PNS Using the Solvatochromic Dye Nile Red.

BACKGROUND: Myelin is an essential component of the peripheral and central nervous system, enabling fast axonal conduction and supporting axonal integrity; limited tools exist for analysis of myelin composition in-vivo. OBJECTIVE: To demonstrate that the photophysical properties of myelin-incorporated solvatochromic dyes can be exploited to probe the biochemical composition of living peripheral nerve myelin at high spatial resolution. METHODS: Using the myelin-incorporated fluorescent dye Nile Red we sequentially analyzed the spectral characteristics of remyelinating myelin membranes both in-vitro and in-vivo, including in living rats. RESULTS: We demonstrated a consistent bi-phasic evolution of emission spectra during early remyelination, and visually report the reliable biochemical flux of myelin membrane composition in-vitro and in-vivo. CONCLUSIONS: Solvatochromic spectroscopy enables the analysis of myelin membrane maturity during remyelination, and can be performed in-vivo. As the formation of myelin during early-to-late remyelination likely incorporates fluctuating fractions of lipophilic components and changes in lateral membrane mobility, we propose that our spectrochemical data reflects the observation of these biochemical processes.

Early-life injury produces lifelong neural hyperexcitability, cognitive deficit and altered defensive behaviour in the squid Euprymna scolopes.

Injury occurring in the neonatal period in mammals is known to induce plasticity in pain pathways that may lead to pain dysfunction in later life. Whether these effects are unique to the mammalian nervous system is not well understood. Here, we investigate whether similar effects of early-life injury are found in a large-brained comparative model, the cephalopod Euprymna scolopes. We show that the peripheral nervous system of E. scolopes undergoes profound and permanent plasticity after injury of peripheral tissue in the early post-hatching period, but not after the same injury given in the later juvenile period. Additionally, both innate defensive behaviour and learning are impaired by injury in early life. We suggest that these similar patterns of nervous system and behavioural remodelling that occur in squid and in mammals indicate an adaptive value for long-lasting plasticity arising from early-life injury, and suggest that injuries inflicted in very early life may signal to the nervous system that the environment is highly dangerous. Thus, neonatal pain plasticity may be a conserved pattern whose purpose is to set the developing nervous system's baseline responsiveness to threat. This article is part of the Theo Murphy meeting issue 'Evolution of mechanisms and behaviour important for pain'.

Engulfing cells promote neuronal regeneration and remove neuronal debris through distinct biochemical functions of CED-1.

Two important biological events happen coincidently soon after nerve injury in the peripheral nervous system in C. elegans: removal of axon debris and initiation of axon regeneration. But, it is not known how these two events are co-regulated. Mutants of ced-1, a homolog of Draper and MEGF10, display defects in both events. One model is that those events could be related. But our data suggest that they are actually separable. CED-1 functions in the muscle-type engulfing cells in both events and is enriched in muscle protrusions in close contact with axon debris and regenerating axons. Its two functions occur through distinct biochemical mechanisms; extracellular domain-mediated adhesion for regeneration and extracellular domain binding-induced intracellular domain signaling for debris removal. These studies identify CED-1 in engulfing cells as a receptor in debris removal but as an adhesion molecule in neuronal regeneration, and have important implications for understanding neural circuit repair after injury.

A three-layered hollow tubular scaffold as an enhancement of nerve regeneration potential.

A significant clinical challenge in the surgery of peripheral nervous system injured via accidents and natural disease is development of biomimetic grafts which could potentially promote nerve repair and regeneration. Although various engineered neural tissue scaffolds have been proposed to support the neural cell functions, they have not been able to instantaneously mimic the whole characteristics of endogenous microenvironment. In this study, we proposed a three-layered tubular scaffold which could provide appropriate electrical, mechanical and biological properties for peripheral nerve engineering. While the inter layer was graphene (Gr) embedded alginate-polyvinyl alcohol (AP-Gr) fibrous scaffold with well-defined anisotropy, the outer layer was double network scaffold of polycaprolactone fumarate (PCLF) and eggshell membrane (ESM). These two layers were attached together using a polycaprolactone (PCL) fibrous membrane, a middle layer, via a simple melting process. Results showed that while the electrical conductivity of the three-layered scaffold was similar to that of AP-Gr fibrous layer, the strength of the three-layered scaffold was significantly improved compared to AP-Gr and ESM-PCLF (1.5 and 1.1 times, respectively) attributed to well attachment of the two layers. As a proof-of-concept, PC12 cell attachment, proliferation, and alignment were studied on the developed three-layered scaffold. The majority of the cells (55%) aligned (<20°) along the major axis of fibers features. Furthermore, electrical stimulation revealed positive effect on the alignment of PC12 cells and change in the cell morphology. With the ease of fabrication and mechanical robustness, the three-layered scaffold of AP-Gr and ESM-PCLF might be utilized as a versatile system for the engineering of peripheral nerve tissue.

The Use of Stem Cells in Neural Regeneration: A Review of Current Opinion.

Nerve injury is a large problem that produces much pain in patients. Injury to the nervous system causes serious consequences and affects a person's quality of life. The development of tissue engineering has created a brighter future for nerve regeneration, and research has not stopped since the discovery of stem cells. Stem cells are a type of pluripotent cell that exhibits the capacity of selfdifferentiation and proliferation. Many studies have demonstrated the ability of stem cells to differentiate into other types of cells, including neurons, after induction with trophic factors in vivo and in vitro. Scientists have isolated a variety of stem cells from different organs and tissues in the human body and demonstrated that these cells were efficacious in regenerative medicine. The use of these cells provides a non-surgical method for the treatment of neurological diseases, such as nerve defects. However, many problems must be resolved before using these cells in the clinical field. The microenvironment and delivery methods of cells also affect the regeneration process. The present article comprehensively summarizes the progress of stem cells in the field of nerve regeneration in the recent decades.

Effects of ralfinamide in models of nerve injury and chemotherapy-induced neuropathic pain.

Neuropathic pain is among the most common and difficult-to-treat types of chronic pain and is associated with sodium channel malfunction. The sodium channel blocker ralfinamide has exhibited potent analgesic effects in several preclinical pain models and in patients with mixed neuropathic pain syndromes (Phase II trials), but it failed to ameliorate neuropathic low back pain in Phase III trials. It is unclear whether ralfinamide is effective against neuropathic pain induced by specified etiologies. In the present study, the antinociceptive effects of ralfinamide in neuropathic pain models induced by spared nerve injury and chemotherapy were compared in a gabapentin-controlled manner. The effects of ralfinamide on physiological pain were evaluated in mechanical withdrawal, hot plate, and acetic acid writhing tests. We also investigated the effects of ralfinamide on cardiovascular function and locomotor activity. Oral ralfinamide dose-dependently alleviated spared nerve injury-induced allodynia in rats and mice. Ralfinamide increased mechanical withdrawal thresholds in oxaliplatin-induced and paclitaxel-induced neuropathic pain. Ralfinamide did not affect physiological pain, locomotion, or cardiovascular function. Together, ralfinamide attenuated mechanical allodynia in all the neuropathic pain models tested, with subtle differences in efficacy. The effect of ralfinamide is comparable to that of gabapentin, but with no interference in basal mechanical sensitivity. The present study supports the effectiveness of selective sodium channel blockade as an analgesic strategy, as well as the development of compounds similar to ralfinamide.

Functional integration of complex miRNA networks in central and peripheral lesion and axonal regeneration.

New players are emerging in the game of peripheral and central nervous system injury since their physiopathological mechanisms remain partially elusive. These mechanisms are characterized by several molecules whose activation and/or modification following a trauma is often controlled at transcriptional level. In this scenario, microRNAs (miRNAs/miRs) have been identified as main actors in coordinating important molecular pathways in nerve or spinal cord injury (SCI). miRNAs are small non-coding RNAs whose functionality at network level is now emerging as a new level of complexity. Indeed they can act as an organized network to provide a precise control of several biological processes. Here we describe the functional synergy of some miRNAs in case of SCI and peripheral damage. In particular we show how several small RNAs can cooperate in influencing simultaneously the molecular pathways orchestrating axon regeneration, inflammation, apoptosis and remyelination. We report about the networks for which miRNA-target bindings have been experimentally demonstrated or inferred based on target prediction data: in both cases, the connection between one miRNA and its downstream pathway is derived from a validated observation or is predicted from the literature. Hence, we discuss the importance of miRNAs in some pathological processes focusing on their functional structure as participating in a cooperative and/or convergence network.

Functional outcomes of Gartland III supracondylar humerus fractures with early neurovascular complications in children: A retrospective observational study.

This was a retrospective observational study. The aim of this study was to evaluate functional outcomes in children treated for Gartland III supracondylar humerus (SCH) fracture with neurovascular (NV) injuries using validated outcome measures. A secondary goal was to determine whether clinical parameters such as age at injury, sex, weight, fracture site, and/or direction of displacement could predict NV injury at the time of fracture or long-term functional outcomes in these patients.One hundred fifty-four patients of Gartland III SCH fractures between March 2004 and May 2013 were studied retrospectively. The patients were divided into 2 groups according to the presence of NV injury. Medical records and radiographs were reviewed to assess several parameters, including age, sex, weight, treatment intervention, the extremity involved, direction of fracture displacement, and NV injury. Functional outcome was assessed on final follow-up using the Pediatric Outcomes Data Collection Instrument (PODCI) and Quick Disabilities of the Arm, Shoulder, and Hand (Quick DASH) outcome measures. Statistical analysis was used to determine the relationship between NV injury and functional outcomes.There were 33 cases with Gartland III SCH fracture associated with NV injuries (10 cases of vascular compromise, 14 cases of neural injury, and 9 cases involving both vascular compromise and neural injury). There were significant differences between the 2 groups in age (P  =  .048), weight (P  =  .009), and direction of displacement (P  =  .004). Vascular compromise and median nerve injury were most common in fractures with posterolateral displacement, and radial nerve injuries were common in fractures with posteromedial displacement. The mean global function score in the PODCI was 91.4 points, and the mean Quick DASH score was 11.7 points, with excellent functional outcomes. No differences in outcomes were identified based upon age, fracture site, sex, weight, direction of displacement, or operative technique in NV injury patients (P > .05).The majority of patients with Gartland III SCH fractures associated with NV injuries returned to a high functioning level after treatment of their injuries. NV injury does not appear to influence functional outcomes. Good functional results can be expected regardless of age, fracture site, sex, weight, direction of displacement, and operative technique.

Neuropathic Pain: Central vs. Peripheral Mechanisms.

PURPOSE OF REVIEW: Our goal is to examine the processes-both central and peripheral-that underlie the development of peripherally-induced neuropathic pain (pNP) and to highlight recent evidence for mechanisms contributing to its maintenance. While many pNP conditions are initiated by damage to the peripheral nervous system (PNS), their persistence appears to rely on maladaptive processes within the central nervous system (CNS). The potential existence of an autonomous pain-generating mechanism in the CNS creates significant implications for the development of new neuropathic pain treatments; thus, work towards its resolution is crucial. Here, we seek to identify evidence for PNS and CNS independently generating neuropathic pain signals. RECENT FINDINGS: Recent preclinical studies in pNP support and provide key details concerning the role of multiple mechanisms leading to fiber hyperexcitability and sustained electrical discharge to the CNS. In studies regarding central mechanisms, new preclinical evidence includes the mapping of novel inhibitory circuitry and identification of the molecular basis of microglia-neuron crosstalk. Recent clinical evidence demonstrates the essential role of peripheral mechanisms, mostly via studies that block the initially damaged peripheral circuitry. Clinical central mechanism studies use imaging to identify potentially self-sustaining infra-slow CNS oscillatory activity that may be unique to pNP patients. While new preclinical evidence supports and expands upon the key role of central mechanisms in neuropathic pain, clinical evidence for an autonomous central mechanism remains relatively limited. Recent findings from both preclinical and clinical studies recapitulate the critical contribution of peripheral input to maintenance of neuropathic pain. Further clinical investigations on the possibility of standalone central contributions to pNP may be assisted by a reconsideration of the agreed terms or criteria for diagnosing the presence of central sensitization in humans.

Peripheral nervous system injury after high-dose single-fraction image-guided stereotactic radiosurgery for spine tumors.

OBJECTIVE The object of this study was to determine the percentage of high-dose (1800-2600 cGy) single-fraction stereotactic radiosurgery (SF-SRS) treatments to the spine that result in peripheral nervous system (PNS) injury. METHODS All patients treated with SF-SRS for primary or metastatic spine tumors between January 2004 and May 2013 and referred to the Rehabilitation Medicine Service for evaluation and treatment of neuromuscular, musculoskeletal, or functional impairments or pain were retrospectively identified. RESULTS Five hundred fifty-seven SF-SRS treatments in 447 patients resulted in 14 PNS injuries in 13 patients. All injures resulted from SF-SRS delivered to the cervical or lumbosacral spine at 2400 cGy. The overall percentage of SF-SRS treatments resulting in PNS injury was 2.5%, increasing to 4.5% when the thoracic spine was excluded from analysis. The median time to symptom onset following SF-SRS was 10 months (range 4-32 months). The plexus (cervical, brachial, and/or lumbosacral) was affected clinically and/or electrophysiologically in 12 (86%) of 14 cases, the nerve root in 2 (14%) of 14, and both in 6 (43%) of 14 cases. All patients experienced pain and most (93%) developed weakness. Peripheral nervous system injuries were CTCAE Grade 1 in 14% of cases, 2 in 64%, and 3 in 21%. No dose relationship between SF-SRS dose and PNS injury was detected. CONCLUSIONS Single-fraction SRS to the spine can result in PNS injury with major implications for function and quality of life.

Peripheral sensory neuron injury contributes to neuropathic pain in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS)-induced neuropathic pain deteriorates quality of life in patients but is often refractory to treatment. In experimental autoimmune encephalomyelitis (EAE), a rodent model of MS, animals develop neuropathy and inflammation-induced tissue acidosis, which suggests the involvement of acid-sensing ion channels (ASICs). Also, peripheral neuropathy is reported in MS patients. However, the involvement of the peripheral nervous system (PNS) in MS neuropathic pain remains elusive. This study investigated the contribution of ASICs and peripheral neuropathy in MS-induced neuropathic pain. Elicited pain levels were as high in Asic1a-/-, Asic2-/- and Asic3-/- mice as wild-type mice even though only Asic1a-/- mice showed reduced EAE disease severity, which indicates that pain in EAE was independent of disease severity. We thus adopted an EAE model without pertussis toxin (EAEnp) to restrain activated immunity in the periphery and evaluate the PNS contribution to pain. Both EAE and EAEnp mice showed similar pain behaviors and peripheral neuropathy in nerve fibers and DRG neurons. Moreover, pregabalin significantly reduced neuropathic pain in both EAE and EAEnp mice. Our findings highlight the essential role of the PNS in neuropathic pain in EAE and pave the way for future development of analgesics without side effects in the CNS.

AlphaB-crystallin expression correlates with aging deficits in the peripheral nervous system.

In an effort to identify factors that contribute to age-related deficits in the undamaged and injured peripheral nervous system (PNS), we noted that Brady and colleagues found that mice null for a small heat shock protein called alphaB-crystallin (αBC) developed abnormalities early in life that are reminiscent of aging pathologies. Because of our observation that αBC protein levels markedly reduce as wild-type mice age, we investigated whether the crystallin plays a role in modulating age-related deficits in the uninjured and damaged PNS. We show here that the presence of αBC correlates with maintenance of myelin sheath thickness, reducing macrophage presence, sustaining lipid metabolism, and promoting remyelination following peripheral nerve injury in an age-dependent manner. More specifically, animals null for αBC displayed a higher frequency of thinly myelinated axons, enhanced presence of Iba1+ macrophages, and fewer immunoreactive profiles of the cholesterol biosynthesis enzyme, squalene monooxygenase, before and after sciatic nerve crush injury. These findings thus suggest that αBC plays a protective and beneficial role in the aging PNS.

Corneal epithelial cells function as surrogate Schwann cells for their sensory nerves.

The eye is innervated by neurons derived from both the central nervous system and peripheral nervous system (PNS). While much is known about retinal neurobiology and phototransduction, less attention has been paid to the innervation of the eye by the PNS and the roles it plays in maintaining a functioning visual system. The ophthalmic branch of the trigeminal ganglion contains somas of neurons that innervate the cornea. These nerves provide sensory functions for the cornea and are referred to as intraepithelial corneal nerves (ICNs) consisting of subbasal nerves and their associated intraepithelial nerve terminals. ICNs project for several millimeters within the corneal epithelium without Schwann cell support. Here, we present evidence for the hypothesis that corneal epithelial cells function as glial cells to support the ICNs. Much of the data supporting this hypothesis is derived from studies of corneal development and the reinnervation of the ICNs in the rodent and rabbit cornea after superficial wounds. Corneal epithelial cells activate in response to injury via mechanisms similar to those induced in Schwann cells during Wallerian Degeneration. Corneal epithelial cells phagocytize distal axon fragments within hours of ICN crush wounds. During aging, the proteins, lipids, and mitochondria within the ICNs become damaged in a process exacerbated by UV light. We propose that ICNs shed their aged and damaged termini and continuously elongate to maintain their density. Available evidence points to new unexpected roles for corneal epithelial cells functioning as surrogate Schwann cells for the ICNs during homeostasis and in response to injury. GLIA 2017;65:851-863.

Relationship between oxidative stress and inflammation in peripheral and cerebral system of oxonate-induced hyperuricemic rats

To study what kind of role uric acid play on the relationship between oxidative Stress and inflammation in peripheral and cerebral system of oxonate-induced hyperuricemic rats. Twenty-six eight male Wistar rats were divided into two groups randomly. Potassium oxonate was used to establish hyperuricemic model for four weeks. In 2nd and 4th week, uric acid (UA) level, total superoxide dismutase (T-SOD), Gu,Zn-SOD activity and interleukin-1beta (IL-1ß) concentration in serum were determined respectively. In 4th week, one hour after last PO treatment, five rats of every group were given Evans Blue to test blood-brain barrier (BBB) permeability. Other brains were obtained to analysis T-SOD, Gu,Zn-SOD activity and IL-1ß concentration in cerebral system. Meanwhile, brain and kidney were stained with hematoxylin and eosin (H&E) to observe pathological change. In 2nd week, both of T-SOD and Gu,Zn-SOD activity in serum increased obviously (P<0.05) in hyperuricemia rats. However, IL-1ß content didn't change remarkably. In the 4th week, T-SOD activity in model group had become similar with control group, and at the same time IL-1ß content in serum increased significantly (P<0.05). Pathological section showed the structural and functional unit of the kidney had been damaged. On the contrary, both of T-SOD and Gu,Zn-SOD activity in brain increased obviously (P<0.05), but IL-1ß concentration was no significant difference between two groups. In addition, the results of Evans Blue and H&E suggested the integrity of BBB and structure of brain were not changed after PO treatment. The permeability of BBB and form of UA would be potential factors to decide what kind role UA play on keeping balance between anti-oxidative stress and induction of inflammatory response.

Técnicas actuales de reparación nerviosa / Current techniques in peripheral nerve repair

Las lesiones del sistema nervioso periférico son uno de los retos terapéuticos de nuestra especialidad, no sólo por la dificultad técnica e instrumental necesaria para resolverlas, sino por la importancia de sus secuelas y los pobres resultados obtenidos con una deficiente técnica quirúrgica. Para obtener un óptimo resultado, es preceptivo, no sólo realizar un correcto diagnóstico, sino además, conocer y dominar las distintas opciones terapéuticas. El objetivo de la presente revisión es abordar las distintas indicaciones y técnicas quirúrgicas usadas actualmente para el tratamiento de las lesiones nerviosas

The injuries of the peripheral nervous system are one of the therapeutic challenges in our speciality given their technical and instrumental difficulty, the importance of the disability and the few results obtained with a deficient surgical technique. For an optimum result, a correct diagnosis is needed as well as to know and to dominate the different therapeutics options. The objetive of the current review is to deal with the different indications and surgery techniques currently used for the treatment of the nervous injuries

Glutamate signals through mGluR2 to control Schwann cell differentiation and proliferation.

Rapid saltatory nerve conduction is facilitated by myelin structure, which is produced by Schwann cells (SC) in the peripheral nervous system (PNS). Proper development and degeneration/regeneration after injury requires regulated phenotypic changes of SC. We have previously shown that glutamate can induce SC proliferation in culture. Here we show that glutamate signals through metabotropic glutamate receptor 2 (mGluR2) to induce Erk phosphorylation in SC. mGluR2-elicited Erk phosphorylation requires ErbB2/3 receptor tyrosine kinase phosphorylation to limit the signaling cascade that promotes phosphorylation of Erk, but not Akt. We found that Gßγ and Src are involved in subcellular signaling downstream of mGluR2. We also found that glutamate can transform myelinating SC to proliferating SC, while inhibition of mGluR2 signaling can inhibit demyelination of injured nerves in vivo. These data suggest pathophysiological significance of mGluR2 signaling in PNS and its possible therapeutic importance to combat demyelinating disorders including Charcot-Marie-Tooth disease.

Estudio preliminar experimental en ratas: uso de plasma rico en plaquetas en el tratamiento de lesiones agudas de nervios periféricos / Experimental preliminary study in rats: use of platelet rich plasma in the treatment of acute injuries of peripheral nerves

Antecedentes y Objetivos. Si consideramos la importancia social y laboral que han adquirido las lesiones de los nervios periféricos por las graves y permanentes secuelas motoras, sensitivas y vegetativas a que dan lugar, cualquier esfuerzo terapéutico para mejorar los resultados de la reparación nerviosa representa un paso positivo dentro del abordaje general de esta afección. A pesar de realizar una sutura técnicamente perfecta, nunca se logra repoblar el segmento distal con la misma cantidad de axones. Esto hace que se busquen alternativas para potenciar la regeneración nerviosa. Dentro de las terapias emergentes, la utilización de plasma rico en plaquetas (PRP) tiene un efecto beneficioso en la reparación nerviosa. Hasta este momento los estudios se han centrado en la utilización del PRP dentro de injertos o tutores interpuestos entre los cabos y no se ha prestado atención a la aplicación del mismo en la sutura directa. Material y Métodos. Estudiamos 8 ratas Wistar a las que se les seccionaron ambos nervios ciáticos; a una de las suturas se le aplicó PRP y el otro nervio suturado se tomó como caso control. En una segunda etapa realizamos la biopsia de ambos nervios a diferentes tiempos y fijamos con un fluoróforo lipofílico que tiñe las fibras regeneradas. Tomamos 2 grupos: a los 40 días y a los 60 días. Calculamos el índice de función del nervio ciático. Resultados. Los nervios seccionados y tratados con PRP presentaron un adelanto en la recuperación de la función nerviosa medida por pruebas funcionales; confirmamos anatómicamente mediante el estudio histológico del nervio. Conclusiones. Los resultados obtenidos en el estudio indican una estimulación del proceso fisiológico de reparación nerviosa usando PRP (AU)

Background and Objectives. Considering the social and laboral importance acquired by peripheral nerve injuries and the serious and permanent motor, sensory and vegetative damage leading to sequels, any therapeutic effort to improve the results of nerve repair represents a positive step in the overall management of this condition. Although a technically perfect suture was made, we never achieved repopulate the distal segment with the same amount of axons. This makes seeking alternatives to enhance nerve regeneration. Among the emerging therapies, the use of platelet rich plasma (PRP) has a beneficial effect on nerve repair. Until now, studies have focused on the use of PRP in grafts or guardians interposed between the ends and have not paid attention in its application in direct suture. Methods. We studied 8 Wistar rats with severed damage of both sciatic nerves: in one nerve suture was applied PRP and the other sutured nerve was taken as case control. In a second stage, both nerve biopsy was performed at different times and fixed with a lipophilic fluorophore which stains regenerated fibers. Controls were taken in 2 groups: 40 days and 60 days. Index sciatic nerve was calculated. Results. The nerves treated with PRP presented a breakthrough in the recovery of nerve function as measured by functional tests and confirmed by histological study of the nerve. Conclusions. The results indicate a physiological process stimulating nerve repair using PRP (AU)