Targeted Delivery of Erythropoietin Hybridized with Magnetic Nanocarriers for the Treatment of Central Nervous System Injury: A Literature Review.

Although the incidence of central nervous system injuries has continued to rise, no promising treatments have been elucidated. Erythropoietin plays an important role in neuroprotection and neuroregeneration as well as in erythropoiesis. Moreover, the current worldwide use of erythropoietin in the treatment of hematologic diseases allows for its ready application in patients with central nervous system injuries. However, erythropoietin has a very short therapeutic time window (within 6-8 hours) after injury, and it has both hematopoietic and nonhematopoietic receptors, which exhibit heterogenic and phylogenetic differences. These differences lead to limited amounts of erythropoietin binding to in situ erythropoietin receptors. The lack of high-quality evidence for clinical use and the promising results of in vitro/in vivo models necessitate fast targeted delivery agents such as nanocarriers. Among current nanocarriers, noncovalent polymer-entrapping or polymer-adsorbing erythropoietin obtained by nanospray drying may be the most promising. With the incorporation of magnetic nanocarriers into an erythropoietin polymer, spatiotemporal external magnetic navigation is another area of great interest for targeted delivery within the therapeutic time window. Intravenous administration is the most readily used route. Manufactured erythropoietin nanocarriers should be clearly characterized using bioengineering analyses of the in vivo size distribution and the quality of entrapment or adsorption. Further preclinical trials are required to increase the therapeutic bioavailability (in vivo biological identity alteration, passage through the lung capillaries or the blood brain barrier, and timely degradation followed by removal of the nanocarriers from the body) and decrease the adverse effects (hematological complications, neurotoxicity, and cytotoxicity), especially of the nanocarrier.

Effects of Pacap on Schwann Cells: Focus on Nerve Injury.

Schwann cells, the most abundant glial cells of the peripheral nervous system, represent the key players able to supply extracellular microenvironment for axonal regrowth and restoration of myelin sheaths on regenerating axons. Following nerve injury, Schwann cells respond adaptively to damage by acquiring a new phenotype. In particular, some of them localize in the distal stump to form the Bungner band, a regeneration track in the distal site of the injured nerve, whereas others produce cytokines involved in recruitment of macrophages infiltrating into the nerve damaged area for axonal and myelin debris clearance. Several neurotrophic factors, including pituitary adenylyl cyclase-activating peptide (PACAP), promote survival and axonal elongation of injured neurons. The present review summarizes the evidence existing in the literature demonstrating the autocrine and/or paracrine action exerted by PACAP to promote remyelination and ameliorate the peripheral nerve inflammatory response following nerve injury.

Recent progress in therapeutic drug delivery systems for treatment of traumatic CNS injuries.

Most therapeutics for the treatment of traumatic central nervous system injuries, such as traumatic brain injury and spinal cord injury, encounter various obstacles in reaching the target tissue and exerting pharmacological effects, including physiological barriers like the blood-brain barrier and blood-spinal cord barrier, instability rapid elimination from the injured tissue or cerebrospinal fluid and off-target toxicity. For central nervous system delivery, nano- and microdrug delivery systems are regarded as the most suitable and promising carriers. In this review, the pathophysiology and biomarkers of traumatic central nervous system injuries (traumatic brain injury and spinal cord injury) are introduced. Furthermore, various drug delivery systems, novel combinatorial therapies and advanced therapies for the treatment of traumatic brain injury and spinal cord injury are emphasized.

Insulin-Like Growth Factor-1-Loaded Polymeric Poly(Lactic-Co-Glycolic) Acid Microspheres Improved Erectile Function in a Rat Model of Bilateral Cavernous Nerve Injury.

BACKGROUND: Previous studies have documented improvement in erectile function after bilateral cavernous nerve injury (BCNI) in rats with the use of pioglitazone. Our group determined this improvement to be mediated by the insulin-like growth factor-1 (IGF-1) pathway. AIM: To eliminate the systemic effects of pioglitazone and evaluate the local delivery of IGF-1 by polymeric microspheres after BCNI in the rat. METHODS: Male Sprague-Dawley rats aged 10-12 weeks were assigned at random to 3 groups: sham operation with phosphate buffered saline (PBS)-loaded microspheres (sham group), crush injury with PBS-loaded microspheres (crush group), and crush injury with IGF-1-loaded microspheres (IGF-1 group). Poly(lactic-co-glycolic) acid microspheres were injected underneath the major pelvic ganglion (MPG). IGF-1 was released at approximately 30 ng/mL/day per MPG per rat. OUTCOMES: Functional results were demonstrated by maximal intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP). Protein-level analysis data of IGF-1 receptor (IGF-1R), extracellular signal-regulated kinase (ERK)-1/2, and neuronal nitric oxide synthase (nNOS) were obtained using Western blot analysis and immunohistochemistry for both the cavernosal tissue and the MPG and cavernous nerve (CN). RESULTS: At 2 weeks after nerve injury, animals treated with IGF-1 demonstrated improved erectile functional recovery (ICP/MAP) at all voltages compared with BCNI (2.5V, P = .001; 5V, P < .001; 7.5V, P < .001). Western blot results revealed that up-regulation of the IGF-1R and ERK-1/2 in both the nervous and erectile tissue was associated with improved erectile function recovery. There were no significant between-group differences in nNOS protein levels in cavernosal tissue, but there was an up-regulation of nNOS in the MPG and CN. Immunohistochemistry confirmed these trends. CLINICAL TRANSLATION: Local up-regulation of the IGF-1R in the neurovascular bed at the time of nerve injury may help men preserve erectile function after pelvic surgery, such as radical prostatectomy, eliminating the need for systemic therapy. STRENGTHS & LIMITATIONS: This study demonstrates that local drug delivery to the MPG and CN can affect the CN tissue downstream, but did not investigate the potential effects of up-regulation of the growth factor receptors on prostate cancer tissue. CONCLUSION: Stimulating the IGF-1R at the level of the CN has the potential to mitigate erectile dysfunction in men after radical prostatectomy, but further research is needed to evaluate the safety of this growth factor in the setting of prostate cancer. Haney NM, Talwar S, Akula PK, et al. Insulin-Like Growth Factor-1-Loaded Polymeric Poly(Lactic-Co-Glycolic) Acid Microspheres Improved Erectile Function in a Rat Model of Bilateral Cavernous Nerve Injury. J Sex Med 2019;16:383-393.

Cannabinoids for the treatment of spasticity.

This review summarizes studies that examined the effectiveness of cannabinoids in treating spasticity, with a focus on understanding the relevance of the existing evidence to paediatric populations. MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched to identify studies that examined the use of cannabinoids in spasticity. We identified 32 studies in adult and paediatric populations. Results were summarized by condition, with adult and paediatric studies considered separately. There is evidence from randomized controlled clinical trials that cannabinoids are more effective than placebo in reducing symptoms of spasticity in adults with multiple sclerosis. Most positive effects were based on patient-rated rather than clinician-rated measures, were modest in size, and should be considered in the context of the narrow therapeutic index of cannabinoids for spasticity and adverse effects. There were comparatively few, and no large studies, of spasticity in conditions other than multiple sclerosis. Few studies have been conducted in paediatric populations. Paediatric studies of spasticity provide low quality evidence and are inadequate to inform clinical practice. Cannabinoids have modest efficacy in reducing muscle spasticity in adults with multiple sclerosis. There is limited evidence of efficacy for cannabinoid use in other conditions, particularly in paediatric populations. Studies in paediatric populations have been of low quality and are insufficient to inform clinical practice.

CANNABINOIDES PARA EL TRATAMIENTO DE LA ESPASTICIDAD: Esta revisión resume los estudios que examinaron la efectividad de los cannabinoides en el tratamiento de la espasticidad, con un enfoque en la comprensión de la relevancia de la evidencia existente para las poblaciones pediátricas. Se realizaron búsquedas en Medline, Embase, PsycINFO y la Biblioteca Cochrane para identificar estudios que examinaron el uso de cannabinoides en la espasticidad. Se identificaron 32 estudios en poblaciones adultas y pediátricas. Los resultados se resumieron por condición, con estudios en adultos y pediátricos considerados por separado. Existe evidencia de ensayos clínicos controlados aleatorios de que los cannabinoides son más efectivos que el placebo para reducir los síntomas de la espasticidad en adultos con esclerosis múltiple. La mayoría de los efectos positivos se basaron en las medidas clasificadas por el paciente en lugar de las clasificadas por el médico, fueron de tamaño modesto y deben considerarse en el contexto del estrecho índice terapéutico de los cannabinoides para la espasticidad y los efectos adversos. Hubo comparativamente pocos, y no hay estudios grandes, de espasticidad en afecciones distintas a la esclerosis múltiple. Se han realizado pocos estudios en poblaciones pediátricas. Los estudios pediátricos de espasticidad proporcionan evidencia de baja calidad y son inadecuados para informar la práctica clínica.

CANABINÓIDES PARA O TRATAMENTO DA ESPASTICIDADE: Esta revisão sintetiza estudos que examinaram a efetividade de canabinóides no tratamento da espasticidade, com foco na compreensão da relevância da evidência existente para populações pediátricas. Medline, Embase, PsycINFO, e Cochrane Library foram pesquisados para identificar estudos que examinaram o uso de canabinóides na espasticidade. Identificamos 32 estudos em populações adultas e pediátricas. Os resultados foram sintetizados por condição com estudos em adultos e pediátricos considerados separadamente. Há evidência de ensaios clínicos randomizados controlados de que os canabinóides são mais efetivos do que placebos na redução de sintomas de espasticidade em adultos com esclerose múltipla. A maioria dos efeitos positivos foram baseados em medidas fornecidas por pacientes e não por clínicos, eram de tamanho modesto, e devem ser considerados no contexto do estreito índice terapêutico dos canabinóides para espasticidade e efeitos adversos. Houve comparativamente menos, e nenhum grande estudo, da espasticidade em condições diferentes da esclerose múltipla. Poucos estudos foram conduzidos em populações pediátricas. Estudos pediátricos da espasticidade fornecem baixa evidência de qualidade e são inadequados para informar a prática clínica.

Application of drug delivery systems for the controlled delivery of growth factors to treat nervous system injury.

Nervous system injury represent the most common injury and was unique clinical challenge. Using of growth factors (GFs) for the treatment of nervous system injury showed effectiveness in halting its process. However, simple application of GFs could not achieve high efficacy because of its rapid diffusion into body fluids and lost from the lesion site. The drug delivery systems (DDSs) construction used to deliver GFs were investigated so that they could surmount its rapid diffusion and retain at the injury site. This study summarizes commonly used DDSs for sustained release of GFs that provide neuroprotection or restoration effects for nervous system injury.

Evaluation of nerve growth factor (NGF) treated mesenchymal stem cells for recovery in neurotmesis model of peripheral nerve injury.

BACKGROUND: Peripheral nerve damages are a relatively common type of the nervous system injuries. Although peripheral nerves show some capacity of regeneration after injury, the extent of regeneration is not remarkable. The present study aimed to evaluate the effect of NGF treated mesenchymal stem cells on regeneration of transected sciatic nerve. MATERIALS AND METHODS: In this experimental study, forty-two male Wistar.rats (180-200 g) were randomly divided into 6 groups (n = 7) including control, Membrane + Cell (Mem + Cell), NGF group, NGF + Cell group, NGF + Mem group and NGF + Mem + Cell group. Regeneration of sciatic nerve was evaluated using behavioral analysis, electrophysiological assessment and histological examination. RESULTS: The rats in the NGF + Mem + Cell group showed significant decrease in sciatic functional index (SFI) and hot water paw immersion test during the 2nd to 8th weeks after surgery. (p < 0.001). At 8 weeks after surgery, electrophysiological findings showed that amplitude increased and latency decreased significantly in NGF + Mem + Cell group (p < 0.001). Measured histological parameters showed that number of nerve fibers, number of vessels and percent of vessel area also increased significantly in NGF + Mem + Cell group (p < 0.05). CONCLUSION: The present study showed that NGF in accompany with mesenchymal stem cells improved electrophysiological and histological indices.

Dickkopf2 rescues erectile function by enhancing penile neurovascular regeneration in a mouse model of cavernous nerve injury.

Penile erection is a neurovascular event and neurologic or vascular disturbances are major causes of erectile dysfunction (ED). Radical prostatectomy for prostate cancer not only induces cavernous nerve injury (CNI) but also results in cavernous angiopathy, which is responsible for poor responsiveness to oral phosphodiesterase-5 inhibitors. Dickkopf2 (DKK2) is known as a Wnt signaling antagonist and is reported to promote mature and stable blood vessel formation. Here, we demonstrated in CNI mice that overexpression of DKK2 by administering DKK2 protein or by using DKK2-Tg mice successfully restored erectile function: this recovery was accompanied by enhanced neural regeneration through the secretion of neurotrophic factors, and restoration of cavernous endothelial cell and pericyte content. DKK2 protein also promoted neurite outgrowth in an ex vivo major pelvic ganglion culture experiment and enhanced tube formation in primary cultured mouse cavernous endothelial cells and pericytes co-culture system in vitro. In light of critical role of neuropathy and angiopathy in the pathogenesis of radical prostatectomy-induced ED, reprogramming of damaged erectile tissue toward neurovascular repair by use of a DKK2 therapeutic protein may represent viable treatment option for this condition.

Application of ultrasound-guided C5 nerve root block using polydeoxyribonucleotide in traumatic C5 nerve root injury caused by fracture of the articular process of the cervical spine: A case report.

RATIONALE: Cervical nerve root injury is one of the complications of traumatic cervical spine fracture. Although one of the most effective treatments to reduce inflammation in nerve root injuries is the use of corticosteroids or nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids and NSAIDs can inhibit bone healing. So, when nerve injury accompanies bone fractures, corticosteroids and NSAIDs have limitations as therapeutic agents. However, polydeoxyribonucleotide (PDRN) may be useful in the treatment of neuropathy or musculoskeletal pain patients with contraindication of the use of corticosteroids because of its anti-inflammatory effect, as revealed in previous studies. To the best of our knowledge, there has been no report of treatment of traumatic nerve root injury due to an articular process fracture with an ultrasound-guided cervical nerve root block (NRB) using PDRN. PATIENTS CONCERNS: A 54-year-old female patient with motor weakness of the left upper extremity and tingling sensation in the left neck and shoulder. DIAGNOSES:: traumatic C5 nerve root injury due to a fracture of the left articular process in the C4 spine. INTERVENTION: Ultrasound-guided C5 NRB using PDRN. OUTCOMES: Her motor weakness and sensory symptoms of the left upper extremity were significantly improved after treatment using an ultrasound-guided C5 NRB using PDRN. LESSONS: Although it is impossible to draw a conclusion from a single case report, we suggest the ultrasound-guided NRB using PDRN could be a useful treatment for alleviating motor weakness and neuropathic pain caused by traumatic spinal nerve root injury in situations where corticosteroids cannot be used.

Methods of Drug Delivery in Neurotrauma.

The central nervous system (CNS) is protected by blood-brain barrier (BBB) and blood-cerebrospinal-fluid (CSF) barrier that limit toxic agents and most molecules from penetrating the brain and spinal cord. However, these barriers also prevent most pharmaceuticals from entering into the CNS. Drug delivery to the CNS following neurotrauma is complicated. Although studies have shown BBB permeability increases in various TBI models, it remains as the key mitigating factor for delivering drugs into the CNS. The commonly used methods for drug delivery in preclinical neurotrauma studies include intraperitoneal, subcutaneous, intravenous, and intracerebroventricular delivery. It should be noted that for a drug to be successfully translated into the clinic, it needs to be administered preclinically as it would be anticipated to be administered to patients. And this likely leads to better dose selection of the drug, as well as recognition of any possible side effects, prior to transition into a clinical trial. Additionally, novel approach that is noninvasive and yet circumvents BBB, such as drug delivery through nerve pathways innervating the nasal passages, needs to be investigated in animal models, as it may provide a viable drug delivery method for patients who sustain mild CNS injury or require chronic treatments. Therefore, the focus of this chapter is to present rationales and methods for delivering drugs by IV infusion via the jugular vein, and intranasally in preclinical studies.

Advanced and High-Throughput Method for Mitochondrial Bioenergetics Evaluation in Neurotrauma.

Mitochondrial dysfunction is one of the key posttraumatic neuropathological events observed in various experimental models of traumatic brain injury (TBI). The extent of mitochondrial dysfunction has been associated with the severity and time course of secondary injury following brain trauma. Critically, several mitochondrial targeting preclinical drugs used in experimental TBI models have shown improved mitochondrial bioenergetics, together with cortical tissue sparing and cognitive behavioral outcome. Mitochondria, being a central regulator of cellular metabolic pathways and energy producer of cells, are of a great interest for researchers aiming to adopt cutting-edge methodology for mitochondrial bioenergetics assessment. The traditional way of mitochondrial bioenergetics analysis utilizing a Clark-type oxygen electrode (aka. oxytherm) is time-consuming and labor-intensive. In the present chapter, we describe an advanced and high-throughput method for mitochondrial bioenergetics assessments utilizing the Seahorse Biosciences XF(e)24 Flux Analyzer. This allows for simultaneous measurement of multiple samples with higher efficiency than the oxytherm procedure. This chapter provides helpful guidelines for conducting mitochondrial isolation and studying mitochondrial bioenergetics in brain tissue homogenates following experimental TBI.

Neuroprotective Effects of Dexmedetomidine Against Hypoxia-Induced Nervous System Injury are Related to Inhibition of NF-κB/COX-2 Pathways.

Dexmedetomidine has been reported to provide neuroprotection against hypoxia-induced damage. However, the underlying mechanisms remain unclear. We examined whether dexmedetomidine's neuroprotective effects were mediated by the NF-κB/COX-2 pathways. Adult male C57BL/6 mice were subjected to a 30-min hypoxic treatment followed by recovery to normal conditions. They received dexmedetomidine (16 or 160 µg/kg) or 25 mg/kg atipamezole, an α2-adrenoreceptor antagonist, intraperitoneally before exposure to hypoxia. The whole brain was harvested 6, 18, or 36 h after the hypoxia to determine the histopathological outcome and cleaved caspase-3, Bax/Bcl, NF-κB, and COX-2 levels. Hypoxia treatment induced significant neurotoxicity, including destruction of the tissue structure and upregulation of the protein levels of caspase-3, the ratio of Bax/Bcl-2, NF-κB, and COX-2. Dexmedetomidine pretreatment effectively improved histological outcome and restored levels of caspase-3, the Bax/Bcl-2 ratio, NF-κB, and COX-2. Atipamezole reversed the neuroprotection induced by dexmedetomidine. Neuroprotection was achieved by PDTC and NS-398, inhibitors of NF-κB and COX-2, respectively. Dexmedetomidine use before hypoxia provides neuroprotection. Inhibition of NF-κB/COX-2 pathways activation may contribute to the neuroprotection of dexmedetomidine.

Therapeutics targeting the inflammasome after central nervous system injury.

Innate immunity is part of the early response of the body to deal with tissue damage and infections. Because of the early nature of the innate immune inflammatory response, this inflammatory reaction represents an attractive option as a therapeutic target. The inflammasome is a component of the innate immune response involved in the activation of caspase 1 and the processing of pro-interleukin 1ß. In this article, we discuss the therapeutic potential of the inflammasome after central nervous system (CNS) injury and stroke, as well as the basic knowledge we have gained so far regarding inflammasome activation in the CNS. In addition, we discuss some of the therapies available or under investigation for the treatment of brain injury, spinal cord injury, and stroke.

Effect of local application of transforming growth factor-ß at the nerve repair site following chronic axotomy and denervation on the expression of regeneration-associated genes. Laboratory investigation.

OBJECTIVES: Although peripheral nerves can regenerate after traumatic injury, functional recovery is often suboptimal, especially after injuries to large nerve trunks such as the sciatic nerve or brachial plexus. Current research with animal models suggests that the lack of functional recovery resides in the lack of sufficient mature axons reaching their targets due to the loss of neurotrophic support by Schwann cells in the distal stump of injured nerves. This study was designed to investigate the effect of one-time application of transforming growth factor-ß (TGF-ß) at the repair site of chronically injured nerve. METHODS: The authors used the rat tibial nerve injury and repair model to investigate the effects of application of physiological concentrations of TGF-ß plus forskolin or forskolin alone in vivo at the repair site on gene and protein expression and axon regeneration at 6 weeks after nerve repair. They used gene expression profiling and immunohistochemical analysis of indicative activated proteins in Schwann cells to evaluate the effects of treatments on the delayed repair. They also quantified the regenerated axons distal to the repair site by microscopy of paraffin sections. RESULTS: Both treatment with forskolin only and treatment with TGF-ß plus forskolin resulted in increased numbers of axons regenerated compared with saline-only control. There was robust activation and proliferation of both Schwann cells and macrophages reminiscent of the processes during Wallerian degeneration. The treatment also induced upregulation of genes implicated in cellular activation and growth as detected by gene array. CONCLUSIONS: Addition of TGF-ß plus forskolin to the repair after chronic nerve injury improved axonal regeneration, probably via upregulation of required genes, expression of growth-associated protein, and reactivation of Schwann cells and macrophages. Further studies are required to better understand the mechanism of the positive effect of TGF-ß treatment on old nerve injuries.

La Palmitoiletanolamida en lesiones nerviosas dolorosas: casos clínicos / No disponible

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New therapeutic advances in CNS injury and repair.

The 9th Global College of Neuroprotection and Neuroregeneration annual meeting was held in cooperation with the 5th International Association of Neurorestoratology and the 4th International Spinal Cord Injury Treatment and Trial Symposium in the beautiful city of Xi'an, Shaanxi Province, China, between 4 and 7 May 2012. This trilateral conference was held in the pleasing ambience of the Sofitel Hotel Complex in Renmin Square, Xi'an. Top Chinese government dignitaries including the National Deputy Health Minister, Vice Governor of Shaanxi Province, Vice President of Xi'an Jiaotong University and Party Secretary of the Medical Association inaugurated the congress. More than 1000 delegates from across the world, including approximately 600 medical researchers from China, participated in this meeting. The theme of this meeting was 'neurorestoration and neurorepair' using stem cell treatment, antibodies and pharmacotherapy, as well as nanomedicine and neurorehabilitation. Preclinical and clinical research was presented and discussed. Use of nanomedicine to enhance neurorepair or diagnosis of neurological diseases in clinical situations was the new attraction in this trilateral meeting. More than 50 leading experts in neuroprotection and neurorestoratology presented their cutting edge research in the area. New features included the Youth Forum in which 12 young scientists presented their innovative results, and more than 30 platform presentations were included. Thus, the trilateral conference of the Global College of Neuroprotection and Neuroregeneration, the International Association of Neurorestoratology and the International Spinal Cord Injury Treatment and Trial Symposium was extremely successful from both the scientific and social perspectives.

[Resveratrol: a neuroprotective polyphenol in the Mediterranean diet]. / Resveratrol: un polifenol neuroprotector de la dieta mediterranea.

INTRODUCTION: Resveratrol is a polyphenol present in grapes, some nuts and dried fruits, and red wine. A number of beneficial properties have been attributed to this compound. Its potential neuroprotective effects are the subject of much research today. AIM: To review the effects of resveratrol, and more particularly those related to its capacity to offer protection against the neurodegeneration associated with several pathologies and traumatic injuries in the central nervous system. DEVELOPMENT: It has been suggested that the daily consumption of red wine, and therefore of resveratrol, could account for the so-called 'French paradox', according to which the population in the south of France, despite eating a diet that is relatively high in saturated fats, presents a low risk of heart disease. From this first evidence of the cardioprotective properties of resveratrol, its study has been extended and equally attractive biopharmacological effects have now been found in many different fields. Thus, neuroprotective effects have been found in models of neurodegeneration (Alzheimer's, Parkinson's or Huntington's disease, or diverse neuropathies), of ischaemia and of brain and spinal cord injury, but further clinical data are still needed in this regard. CONCLUSIONS: Although few studies have been conducted in humans, recent findings in experimental models of neurological pathology are encouraging and open up the doors to future clinical studies that will allow the therapeutic value of resveratrol to be determined.

New strategies for CNS injury and repair using stem cells, nanomedicine, neurotrophic factors and novel neuroprotective agents.

The 8th Annual Conference of the Global College of Neuroprotection and Neuroregeneration (GCNN) was global in the true sense of the word as it was held beyond European boundaries for the first time in the beautiful ambience of the ancient and modern environment of the Hashemite Kingdom of Jordan on 27-30 April 2011. The meeting was organized together with the 4th International Association of Neurorestoratology (IANR; Beijing, China) and the 11th meeting of the American Society for Neural Therapy and Repair (ASNTR; FL, USA). The first joint meeting was extremely successful and attracted more than 600 delegates including top experts, research students and educators from industry, academia, research organizations, universities and medical representatives from across the globe. The focal theme of this meeting was 'Exploring new strategies for neuroregenerative therapy for CNS injury and repair'. The Jordanian Association of Orthopedic Surgeons chaired by Ziad Al Zoubi served as the local host. HRH Princess Basma Bint Talal of Jordan inaugurated the congress. The salient new discoveries and recommendations for future strategies discussed during the meeting are summarized in this article.

Protective effect of GCSB-5, an herbal preparation, against peripheral nerve injury in rats.

AIM OF THE STUDY: GCSB-5 (traditional name: Chungpa-Juhn), an herbal medicine composed of 6 crude herbs (Saposhnikovia divaricata Schiskin, Achyranthis bidentata Blume, Acanthopanax sessiliflorum Seem, Cibotium baromets J. Smith, Glycine max Meriill, and Eucommia ulmoides Oliver), has been widely used in Asia for treatment of neuropathic and inflammatory diseases. This study investigated the protective effect of GCSB-5 against peripheral nerve injury in vitro and in vivo. MATERIALS AND METHODS: After left sciatic nerve transection, rats received oral administration of GCSB-5 (30, 100, 300, and 600 mg/kg), or saline (vehicle), respectively, once daily for 8 weeks. Motor functional recovery and axonal nerve regeneration were evaluated by measurement of sciatic functional index (SFI), sensory regeneration distance, and gastrocnemius muscle mass ratio. The myelinated axon number was counted by morphometric analysis. In the in vitro study, the effects of GCSB-5 on H(2)O(2)-induced oxidative damage in SH-SY5Y cells were investigated by measurement of cell viability, production of reactive oxygen species (ROS), lipid peroxidation, release of lactate dehydrogenease (LDH), and cellular glutathione contents. Neurite outgrowth was also determined. RESULTS: After 8 weeks of nerve transection, SFI, regeneration distance, and gastrocnemius muscle mass ratio and myelinated axon number showed a significant decrease and these decreases were attenuated by GCSB-5. GCSB-5 significantly inhibited H(2)O(2)-induced cell death and oxidative stress, as evidenced by decreases in production of ROS and lipid peroxidation and release of LDH, and by increase in total GSH content. CONCLUSIONS: The neuroprotective effect afforded by GCSB-5 is due in part to reduced oxidative stress.

Uncovering new pharmacological targets to treat neuropathic pain by understanding how the organism reacts to nerve injury.

The neuropathic pain syndrome is complex. Current drugs to treat neuropathic pain, including anticonvulsivants and antidepressants, fail in up to 40-50% of the patients, while in the rest of them total alleviation is not normally achieved. Increased research advances in the neurobiology of neuropathic pain have not translated in more successful pharmacological treatments by the moment, but recent progress in the experimental methods available for this purpose could result in significant advances in the short term. One rational possibility for the pharmaceutical development of new drugs, including target identification, drug design and evaluation studies, could be to focus on mimicking what organism does to limit nerve damage or to enhance the regeneration of injured axons. Following this strategy, neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been postulated as potential pharmacological targets to treat neuropathic pain. In addition, during the last few years, strong scientific evidences point to novel neurotrophic factors, such as pleiotrophin (PTN), as important factors to limit neuropathic pain development because of their remodeling and angiogenic actions in the injured area. This review focuses on recent research advances identifying new pharmacological targets in the treatment of the cause, not only the symptoms, of neuropathic pain.