Translational evaluation of metabolic risk factors impacting DBS efficacy for PD-Related sleep and depressive disorders: preclinical, prospective and cohort studies.

BACKGROUND: Parkinson's disease (PD) is linked with metabolic risk factors including body mass index (BMI), fasting blood glucose (FBG), cholesterol levels, and triglycerides (TG). The extent to which these factors affect motor symptoms, depression, and sleep problems in PD, as well as their role in determining the success of deep brain stimulation (DBS) therapy, is yet to be fully understood. METHODS: This study delved into the effects of metabolic risk factors like BMI, FBG, cholesterol, and TG on the outcomes of DBS in treating PD-related depression and sleep disturbances, across both mouse models and human subjects. RESULTS: DBS showcased noticeable betterment in depression and sleep perturbations in both PD-afflicted mice and patients. High-sugar-high-fat diet aggravates MPTP-induced depression and sleep disorders in mice. PD-afflicted individuals presenting with depressive and sleep disorders demonstrated elevated metrics of BMI, FBG, blood cholesterol, and TG. Remarkably, these metrics bore considerable adverse influences on the efficiency of DBS in ameliorating depression and sleep issues, yet spared motor symptoms. The favorable impacts of DBS persisted for approximately 6 years, post which a significant decline was noted. Importantly, our translational evidence from both murine controls and patient cohorts indicated that antihyperglycemic and antihyperlipidemic therapies bolstered the efficacy of DBS in mitigating PD-related depression and sleep disturbances, without impinging upon motor functions in patients. CONCLUSION: In summary, this research emphasizes that DBS is a powerful treatment option for depression and sleep issues in PD, with its success influenced by metabolic risk factors. It further suggests that incorporating treatments for high blood sugar and cholesterol can enhance the efficacy of DBS in treating depression and sleep disturbances in PD, without impacting motor symptoms, highlighting the importance of metabolic risk management in PD patients receiving DBS.

Sonic Hedgehog reduces inflammatory response, decreases blood-spinal cord barrier permeability, and improves locomotor function recovery in an acute spinal cord injury rat model.

BACKGROUND: Sonic Hedgehog (Shh), extensively researched for its role in early neurogenesis and brain development, has recently been recognized for its neuroprotective potential following neuronal injuries. This study examines the immediate impact of early administered Shh on the local inflammatory response post-acute spinal cord injury in rats. METHODS: Thirty-four female Wistar rats underwent either sham surgery (laminectomy; n = 10) or clip compression/contusion spinal cord injury (SCI) at the T9 level. This was followed by implantation of an osmotic pump and a subdural catheter for continuous intrathecal delivery of Shh (n = 12) or placebo (NaCl; n = 12). Locomotor function was assessed at 3- and 7-days post-injury (dpi) using the Basso, Beattie, and Bresnahan (BBB) score and the Gridwalk test. Animals were euthanized after 3 or 7 days for immunohistochemical analysis of the local inflammatory reaction and immune cell migration. RESULTS: Shh-treated rats demonstrated significant hindlimb movement and coordination improvements at 7 days post-injury, compared to controls. This enhancement was accompanied by a significant reduction in both immune cell presence and blood plasma products within spinal cord lesions, suggesting Shh's dual role in modulating immune cell migration and maintaining the integrity of the blood-spinal cord barrier. Separately, these Shh-treated rats also showed an increase in M(IL-4) polarization of macrophages, further underlining the potential therapeutic impact of Shh in post-injury recovery. Notably, these effects were not evident at three days post-injury. CONCLUSION: Shh application at 7 days post-injury showed immunomodulatory effects, possibly via enhanced blood-spinal cord barrier integrity, reduced immune cell migration, and increased anti-inflammatory immune cell differentiation. These mechanisms collectively contribute to enhanced locomotor recovery.

The injection of maternal B complex vitamin during the transition period: The impact on performance, thyroid hormones levels and immunological parameters in the Sannen goats and their kids, as well as the faeces status of newborn kids.

BACKGROUND: It is proven that B vitamins through promote a wide range of metabolic pathways in animals as cofactors improve animal performance. OBJECTIVES: This study was conducted to investigate the impacts of maternal B complex vitamin injection on performance and plasma parameters in goats and their offspring, as well as the faeces status of newborn kids. METHODS: In this research, the pregnant goats (3 years old) were randomly divided into two groups: the control group (without B complex vitamin injection) and the B complex vitamin group (5 mL B complex vitamin injection per animal). The animals were injected with 5 mL B complex vitamin twice during the transition period (5 weeks pre- and 5 weeks post-kidding). The goats during the transition period and kids on days 10, 20 and 30 were weighed. Feed intake by goats and consumption of milk and starter in kids were recorded daily. The dry matter digestibility by kids was tested by collecting samples of faeces and feed for 5 days in the last week. Chemical analysis was determined using the AOAC method. The kids' faeces were prepared daily during the study. The blood samples of goats and newborn kids were taken 7 days after kidding. Then, levels of B group vitamin, as well as concentrations of liver enzymes, thyroid hormones and immunological parameters, were determined in plasma of goat and their offspring. In addition, concentrations of glucose and insulin were measured in goat plasma (Asadi et al., 2024). RESULTS: According to results, the performances of goats and their offspring, as well as kids' faeces status, were improved by maternal B complex vitamin injection (p < 0.0001). The levels of cobalamin, pyridoxine, thiamine, folic acid, nicotinic, pantothenic and unconjugated pteridine increased in the plasma of goats and their kids in the B complex vitamin group compared with the control group during the transition period (p < 0.0001). Injection of maternal B complex vitamin raised the plasma levels of triiodothyronine and tetraiodothyronine, immunoglobulin G and immunoglobulin M in goats and their offspring (p < 0.0001). Higher levels of glucose and lower levels of insulin were determined in the goats injected with B complex vitamin (p < 0.0001). CONCLUSIONS: These results suggest that maternal B complex vitamin injection is required for the improvement of performance, health status and the blood plasma parameters in pregnant goats and their kids.

Vaccine-based immunotherapy and related preclinical models for glioma.

Glioma, the most common primary malignant tumor in the central nervous system (CNS), lacks effective treatments, and >60% of cases are glioblastoma (GBM), the most aggressive form. Despite advances in immunotherapy, GBM remains highly resistant. Approaches that target tumor antigens expedite the development of immunotherapies, including personalized tumor-specific vaccines, patient-specific target selection, dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) and T cell receptor (TCR) T cells. Recent studies show promising results in treating GBM and lower-grade glioma (LGG), fostering hope for future immunotherapy. This review discusses tumor vaccines against glioma, preclinical models in immunological research, and the role of CD4+ T cells in vaccine-induced antitumor immunity. We also summarize clinical approaches, challenges, and future research for creating more effective vaccines.

The effects of MitoQ as a mitochondrial-targeted antioxidant in a plant-based extender on buck sperm quality parameters during cryopreservation.

Sperm cryopreservation plays an important role in the artificial insemination (AI) industry of small ruminants. It, however the use of frozen-thawed goat semen is limited due to the insufficient number of sperm with good biological functions. Mitochondria are the most sensitive organelles to cryopreservation damage in sperm. This study was conducted to determine the effects of MitoQ, the mitochondrial-targeted antioxidant, in a plant-based extender on the quality parameters of Markhoz goat sperm after the freezing and thawing process. Semen samples were collected and diluted in the extender, divided into five equal aliquots and supplemented with 0, 1, 10, 100 and 1000 nM MitoQ and cryopreserved in liquid nitrogen. After thawing, sperm motility, membrane functionality, abnormal morphology, mitochondrial activity, acrosome integrity, lipid peroxidation (LPO), DNA fragmentation, reactive oxygen species (ROS) concentration, viability and apoptotic-like changes were measured. The use of 10 and 100 nM MitoQ resulted in higher (P≤0.05) total motility (TM), progressive motility (PM), viability, membrane functionality, mitochondrial activity, and acrosome integrity compared to the other groups. On the other hand, LPO, apoptotic-like changes, DNA fragmentation and ROS concentration were lower (P≤0.05) in MQ10 and MQ100 groups compared to the other groups. MitoQ has no effect (P>0.05) on sperm abnormal morphology and velocity parameters. In conclusion, MitoQ can reduce oxidative stress by regulating mitochondrial function during the cryopreservation process of buck sperm and could be an effective additive in the cryopreservation media to protect sperm quality.

Acute alcohol consumption modulates corneal biomechanical properties as revealed by optical coherence elastography.

Acute alcohol ingestion has been found to impact visual functions, including eye movement, but its effects on corneal biomechanical properties remain unclear. This study aimed to investigate the influence of acute alcohol consumption on corneal biomechanical properties using optical coherence elastography (OCE). An air-coupled ultrasound transducer induced elastic waves in mice corneas in vivo, and a high-resolution phase-sensitive optical coherence tomography (OCT) system tracked the mechanical waves to quantify the elastic wave speed. In vivo measurements were performed on three groups of age- and gender-matched mice: control, placebo (administered saline), and alcohol (administered ethanol) groups. Longitudinal measurements were conducted over a one-hour period to assess acute temporal changes in wave speeds, which are associated with inherent biomechanical properties of the cornea. The results showed a significant decrease in wave speed for the alcohol group after 10 min of ingestion in comparison to pre-ingestion values (p = 0.0096), whereas the temporal wave speed changes for the placebo group were statistically insignificant (p = 0.076). In contrast, the control group showed no significant changes in elastic wave speed and corneal thickness. Furthermore, a significant difference was observed between the wave speeds of the placebo and alcohol groups at each measurement time point between 10 and 50 min (p < 0.05), though both groups exhibited a similar trend in corneal thickness change. The findings of this study have important implications for clinical assessments and research in corneal disorders, highlighting the potential of OCE as a valuable tool for evaluating such changes.

Noninvasive Tracking of Embryonic Cardiac Dynamics and Development with Volumetric Optoacoustic Spectroscopy.

Noninvasive monitoring of cardiac development can potentially prevent cardiac anomalies in adulthood. Mouse models provide unique opportunities to study cardiac development and disease in mammals. However, high-resolution noninvasive functional analyses of murine embryonic cardiac models are challenging because of the small size and fast volumetric motion of the embryonic heart, which is deeply embedded inside the uterus. In this study, a real time volumetric optoacoustic spectroscopy (VOS) platform for whole-heart visualization with high spatial (100 µm) and temporal (10 ms) resolutions is developed. Embryonic heart development on gestational days (GDs) 14.5-17.5 and quantify cardiac dynamics using time-lapse-4D image data of the heart is followed. Additionally, spectroscopic recordings enable the quantification of the blood oxygenation status in heart chambers in a label-free and noninvasive manner. This technology introduces new possibilities for high-resolution quantification of embryonic heart function at different gestational stages in mammalian models, offering an invaluable noninvasive method for developmental biology.

The first case of isolation of Magnusiomyces capitatus from the oral cavity of an addicted patient.

Magnusiomyces capitatus (M. capitatus) is an emerging opportunistic yeast, rarely found as a causal agent of invasive fungal infection. In this study, we report a 31-year-old man infected with M. capitatus in the oral cavity, with a history of heroin and amphetamine abuse. M. capitatus was isolated through culture and microscopic analysis and identified by PCR amplification of the ITS DNA region. Based on the in vitro antifungal susceptibility test, the lowest MICs for M. capitatus were recorded for nystatin, itraconazole, and amphotericin, while higher MICs were observed for caspofungin and fluconazole. Treatment with nystatin successfully eliminated M. capitatus and relieved the clinical symptoms. This study presents the first case of M. capitatus in a patient with substance use disorder, manifesting as a plaque-like ulcer in the oral cavity.

The effect of maternal organic manganese supplementation on performance, immunological status, blood biochemical and antioxidant status of Afshari ewes and their newborn lambs in transition period.

It has been documented that adequate maternal manganese (Mn) status is vital for performance and health of ewes and their newborn lambs. However, required level and form of dietary Mn in ruminants are not well defined. The current study was conducted to evaluate the effect of maternal organic Mn supplementation on performance, immunological status, blood biochemical and antioxidant status of Afshari ewes and their newborn lambs in transition period. For this purpose, various organic Mn concentrations were utilized as a supplementary ingredient in formulating the diets of ewes. The ewes were randomly allocated into three groups, fed with 0, and 80 mg/kg organic Mn supplemented diet. At the end of the experiment, the parameters including the performance of newborn lambs, as well as biochemical factors, immune status and antioxidant status in ewes and their newborn lambs were evaluated. The results showed a significant increase in the plasma concentrations of Mn, glucose, insulin, thyroid hormones (T3 , T4 ) and enzymatic antioxidants (SOD, GPX , CAT) in ewes and their newborn lambs that were treated with maternal organic Mn. Moreover, inorganic Mn treatments, the concentration of IgG in newborn lamb's plasma, and colostrum of ewes increased. According to this research, organic Mn acts as a valuable and safe supplementary material that could be exploited for enhancing health of ewes and their newborn lambs.

Worldwide prevalence of extended-spectrum ß-lactamases-producing uropathogenic Escherichia coli isolates among kidney transplant patients: a systematic review and meta-analysis.

A significant proportion of urinary tract infections (UTIs), typically affecting kidney transplant patients (KTPs), is attributed to the presence of extended-spectrum ß-lactamases (ESBLs) and multi-drug resistance (MDR) in Escherichia coli strains. For this reason, the current meta-analysis was conducted to summarize the frequency of ESBL-producing UPEC among KTPs. A systematic search was conducted to identify studies in the Web of Science, PubMed, Embase, and Scopus electronic databases between 2000 and 2021. Finally, 16 articles were selected for data extraction, and meta-analysis was performed using the metaprop command in the STATA (version 11) software. From those studies, the pooled prevalence of ESBL-producing uropathogenic E. coli (UPEC) isolates was 40%. The subcategory analysis results based on continent indicated that Asian countries had the highest rate of ESBL-producing isolates with 45%, followed by 40%, 28%, and 16% in Europe, South America and North America, respectively. Uncomfortably, high level of UPEC isolates in the current investigation was ESBL-producing isolates. These isolates pose a high serious threat to public health because they can contribute to the spread of antimicrobial resistance in the local population and hasten the ineffectiveness of the majority of commonly prescribed antibiotics for the treatment of UTI in KTPs and other patients.

Nanobomb optical coherence elastography in multilayered phantoms.

Many tissues are composed of layered structures, and a better understanding of the changes in the layered tissue biomechanics can enable advanced guidance and monitoring of therapy. The advent of elastography using longitudinally propagating shear waves (LSWs) has created the prospect of a high-resolution assessment of depth-dependent tissue elasticity. Laser activation of liquid-to-gas phase transition of dye-loaded perfluorocarbon (PFC) nanodroplets (a.k.a., nanobombs) can produce highly localized LSWs. This study aims to leverage the potential of photoactivation of nanobombs to incudce LSWs with very high-frequency content in wave-based optical coherence elastography (OCE) to estimate the elasticity gradient with high resolution. In this work, we used multilayered tissue-mimicking phantoms to demonstrate that highly localized nanobomb (NB)-induced LSWs can discriminate depth-wise tissue elasticity gradients. The results show that the NB-induced LSWs rapidly change speed when transitioning between layers with different mechanical properties, resulting in an elasticity resolution of ∼65 µm. These results show promise for characterizing the elasticity of multilayer tissue with a fine resolution.

Thiadiazole - A promising structure in design and development of anti-Alzheimer agents.

The design and development of effective multitargeted agents in treating Alzheimer disease (AD) has always been a hot topic in the field of drug discovery. Since AD is a multifactorial disorder, various key hidden players such as deficit of acetylcholine (ACh), tau-protein aggregation, and oxidative stress have been associated with the incidence and progress of AD. In pursuit of improving efficacy and expanding the range of pharmacological activities of current AD drugs, the molecular hybridization method is also used intensively. Five-membered heterocyclic systems such as thiadiazole scaffolds have previously been shown to have therapeutic activity. Thiadiazole analogs as an anti-oxidant compound have been known to include a wide range of biological activity from anti-cancer to anti-Alzheimer properties. The suitable pharmacokinetic and physicochemical properties of the thiadiazole scaffold have introduced it as a therapeutic target in medicinal chemistry. The current review portrays the critical role of the thiadiazole scaffold in the design of various compounds with potential effects in the treatment of Alzheimer's disease. Furthermore, the rationale used behind hybrid-based design strategies and the outcomes achieved through the hybridization of Thiadiazole analogs with various core structures have been discussed. In addition, the data in the present review may help researchers in the design of new multidrug combinations that may provide new options for the treatment of AD.

Antioxidant Compounds in the Treatment of Alzheimer's Disease: Natural, Hybrid, and Synthetic Products.

Alzheimer's disease (AD) which is associated with cognitive dysfunction and memory lapse has become a health concern. Various targets and pathways have been involved in AD's progress, such as deficit of acetylcholine (ACh), oxidative stress, inflammation, ß-amyloid (Aß) deposits, and biometal dyshomeostasis. Multiple pieces of evidence indicate that stress oxidative participation in an early stage of AD and the generated ROS could enable neurodegenerative disease leading to neuronal cell death. Hence, antioxidant therapies are applied in treating AD as a beneficial strategy. This review refers to the development and use of antioxidant compounds based on natural products, hybrid designs, and synthetic compounds. The results of using these antioxidant compounds were discussed with the given examples, and future directions for the development of antioxidants were evaluated.

Egg yolk plasma enriched with ß-carotene through the diet of laying hens and adding it to the extender improves the quality of frozen semen in Arabic stallions.

Equine semen cryopreservation is one of the major procedures for the genetic conservation of rare and endangered genotypes. The current study was conducted to evaluate the effect of egg yolk plasma (EYP) enriched with ß-carotene as an antioxidant supplement on INRA-96 extender regarding freezing Arabic stallion sperm. For this purpose, ß-carotene various concentrations were utilized as a supplementary ingredient in formulating the diets of laying hens. Birds were randomly divided into four groups, fed with 0 (control), 500, 1000 and 2000 mg/kg in a supplemented diet with ß-carotene. Subsequently, various variants of enriched extender (INRA-96 + 2.5% glycerol [G]) were gained by adding 2% EYP from four treatment groups. The sperm characteristics, including motility, viability, morphology, plasma membrane integrity (HOS test), lipid peroxidation (MDA) and DNA fragmentation, were evaluated after thawing. According to the results obtained in this study, the addition of EYP from T2 and T4 (500 and 2000 mg/kg of ß-carotene in hens' diet) to the extender (INRA-96 + 2.5% G) leads to an increase in total motility (50.50% and 49.49%, respectively), progressive motility (32.6% and 31.8%, respectively), viability (68.7% and 66.1%, respectively) and plasma membrane integrity (57.7% and 50.6%, respectively). Moreover, lipid peroxidation (1.3 and 1.4 nmol/mL, respectively) and DNA fragmentation (8.6% and 9.9%, respectively) were diminished using the mentioned treatments. However, sperm morphology was not affected by the treatments. In the current study, we concluded that the optimal concentration of ß-carotene in the laying hen's diet (500 mg/kg) could reveal the best results about sperm quality. So, EYP enriched with ß-carotene acts as a valuable natural and safe supplementary material that could be exploited for enhancing stallion sperm quality in cryopreservation conditions.

Neuromyotonia with Central Nervous System Lesions following Quadrivalent Human Papilloma Virus Vaccination.

Neuromyotonia is a rare peripheral nerve hyperexcitability syndrome often associated with antibodies directed against contactin-associated protein-like 2 and leucine-rich, glioma inactivated 1. The quadrivalent human papilloma virus vaccine Gardasil®, first approved in 2006, is known to be a highly effective prophylaxis against papillomavirus types 6, 11, 16, and 18. Molecularly, this non-infectious recombinant vaccine is based on purified L1 proteins from the human papilloma virus capsid. Since the approval of this vaccine, several studies have investigated its safety regarding the occurrence of autoimmune conditions following application. Here, we present the first case of neuromyotonia with active Gadolinium enhancing demyelinating central nervous system lesions following vaccination with Gardasil®.

Trichophyton indotineae-An Emerging Pathogen Causing Recalcitrant Dermatophytoses in India and Worldwide-A Multidimensional Perspective.

Trichophyton (T.) indotineae is a newly identified dermatophyte species that has been found in a near-epidemic form on the Indian subcontinent. There is evidence of its spread from the Indian subcontinent to a number of countries worldwide. The fungus is identical to genotype VIII within the T. mentagrophytes/T. interdigitale species complex, which was described in 2019 by sequencing the Internal Transcribed Spacer (ITS) region of ribosomal DNA of the dermatophyte. More than 10 ITS genotypes of T. interdigitale and T. mentagrophytes can now be identified. T. indotineae causes inflammatory and itchy, often widespread, dermatophytosis affecting the groins, gluteal region, trunk, and face. Patients of all ages and genders are affected. The new species has largely displaced other previously prevalent dermatophytes on the Indian subcontinent. T. indotineae has become a problematic dermatophyte due to its predominantly in vitro genetic resistance to terbinafine owing to point mutations of the squalene epoxidase gene. It also displays in vivo resistance to terbinafine. The most efficacious drug currently available for this terbinafine-resistant dermatophytoses, based on sound evidence, is itraconazole.

Evaluation of catalase activity of clinical and environmental isolates of Aspergillus species.

Background and Objectives: Catalases are a good scavenger of H2O2 which degrades hydrogen peroxide into water and oxygen. They are considered as a virulence factor that are present in both spores and hypha of fungi. There is limited data regarding catalase activity in Aspergillus species. This study aimed to assess the mycelial catalase activity of clinical and environmental isolates of Aspergillus niger, A. tubingensis, A. flavus, A. luchuensis, A. piperis and A. terreus. Materials and Methods: Briefly, clinical and environmental Aspergillus species were used in the current study. Catalase activity was assessed for both groups of isolates including 13 A. flavus (12 clinical, 1 environmental), 13 A. terreus (8 clinical, 5 environmental), 26 A. tubingensis (13 clinical, 13 environmental), and 44 A. niger (25 environmental, 19 clinical) species. Fungal balls of mycelia were separated from the liquid culture and were crushed using homogenizer. The supernatants were collected and used for a catalase activity assay. Results: Totally, in our study 98 Aspergillus including 45 environmental and 53 clinical isolates were assessed for catalase activity. High catalase activity was detected among environmental Aspergillus species (Mean= 1.62 mU/ml) and the mean of mycelial catalase activity among clinical A. terreus isolates was higher than environmental strains. Conclusion: In summary, mycelial catalase activity varied among species and environmental isolates demonstrated higher catalase activity. Totally a significant difference was found between clinical and environmental Aspergillus isolates.

Milk Supplemented with Organic Iron Improves Performance, Blood Hematology, Iron Metabolism Parameters, Biochemical and Immunological Parameters in Suckling Dalagh Lambs.

This study was conducted to investigate the effect of milk supplemented with organic iron on performance, blood hematology, iron metabolism parameters, biochemical and immunological parameters in suckling lambs. Thirty-six newborn Dalagh lambs were randomly divided into three groups with 12 replications. The control group was fed with milk without organic iron. The other two groups were fed milk supplemented with 25 and 50 mg/d organic iron, respectively. During the experiment, increased daily weight gain and total body weight were observed in the iron-supplemented groups. An increase in the levels of red blood cell, hemoglobin, hematocrit, mean corpuscular hemoglobin, and mean corpuscular concentration in iron supplemented groups was indicated. Consumption of organic iron caused a significant decrease in plasma copper concentration. Total antioxidant status level was lower, but levels of glutathione peroxidase, superoxide dismutase, and catalase were higher in iron supplemented groups. In organic iron supplemented groups, insulin and thyroid hormones levels were significantly increased, and glucose level was significantly decreased. In organic iron supplemented groups, alkaline phosphatase level significantly increased, and aminotransferase level significantly decreased. Overall, the use of organic iron in the milk improved the performance and health in suckling lambs, and since a lower level of supplementation is naturally preferable, supplementation of milk with 25 mg/d organic iron is recommended.

The Sonic Hedgehog Pathway Modulates Survival, Proliferation, and Differentiation of Neural Progenitor Cells under Inflammatory Stress In Vitro.

The Sonic Hedgehog protein (Shh) has been extensively researched since its discovery in 1980. Its crucial role in early neurogenesis and endogenous stem cells of mature brains, as well as its recently described neuroprotective features, implicate further important effects on neuronal homeostasis. Here, we investigate its potential role in the survival, proliferation, and differentiation of neural precursors cells (NPCs) under inflammatory stress as a potential adjunct for NPC-transplantation strategies in spinal cord injury (SCI) treatment. To this end, we simulated an inflammatory environment in vitro using lipopolysaccharide (LPS) and induced the Shh-pathway using recombinant Shh or blocked it using Cyclopamine, a potent Smo inhibitor. We found that Shh mediates the proliferation and neuronal differentiation potential of NPCs in vitro, even in an inflammatory stress environment mimicking the subacute phase after SCI. At the same time, our results indicate that a reduction of the Shh-pathway activation by blockage with Cyclopamine is associated with reduced NPC-survival, reduced neuronal differentiation and increased astroglial differentiation. Shh might thus, play a role in endogenous NPC-mediated neuroregeneration or even be a potent conjunct to NPC-based therapies in the inflammatory environment after SCI.