Nerve growth factor (NGF) is a neurotrophic peptide largely revealed for its ability to regulate the growth and survival of peripheral sensory, sympathetic, and central cholinergic neurons. The pro-survival and regenerative properties of neurotrophic factors propose a therapeutic potential in a wide range of brain diseases, and NGF, in particular, has appeared as an encouraging potential treatment. In this review, a summary of clinical studies regarding NGF and its therapeutic effects published to date, with a specific interest in the pediatric context, will be attempted. NGF has been studied in neurological disorders such as hypoxic-ischemic encephalopathy, traumatic brain injury, neurobehavioral and neurodevelopmental diseases, congenital malformations, cerebral infections, and in oncological and ocular diseases. The potential of NGF to support neuronal survival, repair, and plasticity in these contexts is highlighted. Emerging therapeutic strategies for NGF delivery, including intranasal administration as well as advanced nanotechnology-based methods, are discussed. These techniques aim to enhance NGF bioavailability and target specificity, optimizing therapeutic outcomes while minimizing systemic side effects. By synthesizing current research, this review underscores the promise and challenges of NGF-based therapies in pediatric neurology, advocating for continued innovation in delivery methods to fully harness NGF\'s therapeutic potential.

UNASSIGNED: Hippocampal neurogenesis is critical for improving learning, memory, and spatial navigation. Inhabiting and navigating spatial complexity is key to stimulating adult hippocampal neurogenesis (AHN) in rodents because they share similar hippocampal neuroplasticity characteristics with humans. AHN in humans has recently been found to persist until the tenth decade of life, but it declines with aging and is influenced by environmental enrichment. This systematic review investigated the impact of spatial complexity on neurogenesis and hippocampal plasticity in rodents, and discussed the translatability of these findings to human interventions.
UNASSIGNED: Comprehensive searches were conducted on three databases in English: PubMed, Web of Science, and Scopus. All literature published until December 2023 was screened and assessed for eligibility. A total of 32 studies with original data were included, and the process is reported in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement and checklist.
UNASSIGNED: The studies evaluated various models of spatial complexity in rodents, including environmental enrichment, changes to in-cage elements, complex layouts, and navigational mazes featuring novelty and intermittent complexity. A regression equation was formulated to synthesize key factors influencing neurogenesis, such as duration, physical activity, frequency of changes, diversity of complexity, age, living space size, and temperature.
UNASSIGNED: Findings underscore the cognitive benefits of spatial complexity interventions and inform future translational research from rodents to humans. Home-cage enrichment and models like the Hamlet complex maze and the Marlau cage offer insight into how architectural design and urban navigational complexity can impact neurogenesis in humans. In-space changing complexity, with and without physical activity, is effective for stimulating neurogenesis. While evidence on intermittent spatial complexity in humans is limited, data from the COVID-19 pandemic lockdowns provide preliminary evidence. Existing equations relating rodent and human ages may allow for the translation of enrichment protocol durations from rodents to humans.

UNASSIGNED: Neurotrophins have been implicated in multiple psychiatric disorders. Nerve Growth Factor (NGF) is one of the major neurotrophins that has attracted much research interest. Therefore, we undertook, to the best of our knowledge, the first scoping review encompassing all major psychiatric disorders and their relation to NGF. This review aimed to identify the current position of NGF in psychiatric research and to outline present gaps in knowledge, which can be answered with a more detailed systematic review in the future.
UNASSIGNED: Suitable studies were identified using PubMed. A total of 20 studies were included in the review: two on bipolar affective disorder (BPAD), three on schizophrenia, seven on depression, and eight on alcohol use disorder.
UNASSIGNED: NGF levels are definitively reduced in BPAD and depression, while NGF levels in schizophrenia decreased further after treatment than in the drug-naïve state. The effect of treatment on NGF levels in depression varied based on treatment modalities and severity of depression. In patients with depression, raised NGF was a predictor of conversion to bipolar disorder (BD). NGF levels were raised in acute alcohol intoxication and withdrawal but normalized slowly as abstinence was maintained. NGF may play a protective role in preventing the toxic ill effect of acute alcohol intoxication on the central nervous system.
UNASSIGNED: Based on current knowledge, NGF levels may be a useful biomarker of a chronic mental stress condition. However, further research is needed before it can be used to identify a specific psychiatric illness or predict treatment response.

The impact of cannabis uses on blood levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) remains uncertain, with conflicting findings reported in the literature. BDNF and NGF both are essential proteins for neuron\'s growth, and their dysregulation is seen in various mental disorders. This study aims to evaluate the relationship between cannabis usage and BDNF and NGF levels due to their potential implications for mental health.
A comprehensive search of electronic databases was performed using appropriate MeSH terms and keywords. Inclusion criteria comprised human studies investigating the relationship between cannabis use and BDNF and NGF levels.
A total of 11 studies met the inclusion criteria and were included. The pooled analysis revealed a nonsignificant association between cannabis use and dysregulated blood levels of BDNF (random-effects model, standardized mean differences [SMD] = .26, 95% CI -.34 to .76, p = .40). The results of our subgroup analysis based on BDNF source showed a nonsignificant between-group difference. For NGF levels, four studies were included, the pooled analysis revealed a nonsignificant association between cannabis use and dysregulated blood levels of NGF (random-effects model, SMD = -.60, 95% CI -1.43 to -.23, p = .16). In both analyses, high heterogeneity was observed among the included studies which is a notable limitation to current meta-analysis.
This systematic review highlights the need for further research to elucidate the relationship between cannabis use and these neurotrophic factors. A better understanding of these associations can contribute to our knowledge of the neurobiological effects of cannabis and inform potential implications for mental health, cognitive function, and neurodegenerative disorders.

OBJECTIVE: The aim of this systematic review is to assess urinary biomarkers studied in children with neurogenic and non-neurogenic lower urinary tract dysfunction (LUTD).
METHODS: The systematic review was conducted in accordance with the PRISMA guidelines. The screening was performed on PUBMED without any publication date limitation. Only original articles were included. Parameters related to the following topics were obtained: study design, characteristics of participants, number of participants, age, control group, types of biomarkers, measurement technique in urine, subgroup analysis, urodynamic findings, and outcome. Dutch Cochrane Checklist (DCC) and level of evidence by EBRO platform were used for quality assessment. Meta-analysis was performed with the Comprehensive Meta-Analysis Version 4 program.
RESULTS: A total of 494 studies were screened and 16 studies were included. 11 (68.75%) were conducted in children with non-neurogenic LUTD and 5 (31.25%) neurogenic LUTD. Nerve growth factor (NGF) was evaluated in 12 studies, brain-derived neurotrophic factor (BDNF) in 5, Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) in 2, transforming growth factor beta-1 (TGF Beta-1) in 2, neutrophil gelatinase-associated lipocalin (NGAL) in 1, and Aquaporin-2 in 1. According to DCC, 10 (62.5%) articles were evaluated on 4 (37.5%) items and 4 articles on 5 items. The average score was 3.91+/-0.56. The level of evidence was found as B for 13 (81.25%) articles and C for 3 (18.75%). In meta-analysis, urinary NGF levels in children with non-neurogenic LUTS were significantly higher than in the healthy control group (Hedges\'s g = 1.867, standard error = 0.344, variance = 0.119, p = 0.0001).
CONCLUSIONS: Urinary biomarkers are promising for the future with their noninvasive features. However, prospective studies with larger sample sizes are needed to better understand the potential of urinary biomarkers to reflect urodynamic and clinical findings in children with LUTD.

To study the process of neuronal differentiation, the human neuroblastoma (SH-SY5Y) and the murine neuroblastoma (Neuro2a) cell lines have proven to be effective models. For this approach, different protocols involving known neurotrophic factors and other molecules, such as retinoic acid (RA), have been assessed to better understand the neuronal differentiation process. Thus, the goal of this manuscript was to provide a brief overview of recent studies that have used protocols to promote neurodifferentiation in SH-SY5Y and Neuro2a cell lines and used acquired morphology and neuronal markers to validate whether differentiation was effective. The published results supply some guidance regarding the relationship between RA and neurotrophins for SH-SY5Y, as well a serum concentrations for both cell lines. Furthermore, they demonstrate the potential application of Neuro2a, which is critical for future research on neuronal differentiation.

With a constantly growing elderly population, incidences of neurodegenerative diseases are also rising and are expected to further increase over the next years, while costing health systems across the world trillions of dollars. Therefore, biomarkers to detect manifestations of brain aging early and interventions to slow down its pace are of great interest. In the last years, the importance of the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the context of cognitive function and the aging brain has increased, besides the already well-established amyloid-beta (Aβ) and tau plaques. Due to their wide range of beneficial health effects as well as their antioxidant and anti-inflammatory properties, a class of secondary plant-metabolites, the so-called polyphenols, gained increasing attention. In this review, we discuss the roles of BDNF, Aβ, NGF, and tau proteins as biomarkers of brain aging and the effect of dietary polyphenol interventions on these biomarkers, assessed via blood analysis, magnetic resonance imaging (MRI), and positron emission tomography (PET).

Endometriosis is diagnosed by laparoscopic surgery. The availability of biomarkers can help understand the pathophysiology and aid in the diagnosis of the condition. In this context, this review aimed to examine levels of expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are increased amongst patients with endometriosis and if they can serve as a potential biomarker. PubMed, CENTRAL, Scopus, Web of Science, and Embase databases were searched for studies comparing BDNF or NGF levels amongst endometriosis patients and controls. Data were pooled for serum and tissue levels of BDNF and NGF. Ten fulfilled the inclusion criteria. On comparing BDNF levels, it was noted that endometrial tissue had significantly higher expression of BDNF levels as compared to controls (SMD: 1.73 95% CI: 0.64, 2.82 I2 = 89%). Similarly, the meta-analysis found significantly higher serum levels of BDNF in endometriosis patients as compared to controls (SMD: 1.66 95% CI: 0.73, 2.59 I2 = 95%). Pooled analysis showed significantly increased levels of NGF in endometrial tissue as compared to controls (SMD: 4.15 95% CI: 0.11, 8.18 I2 = 98%) but with unstable results on sensitivity analysis. Only one study showed higher levels of NGF in serum amongst endometriosis patients. Limited data shows higher expression of BDNF in endometrial lesions and increased serum levels of BDNF in endometriosis patients. Similar results were noted for NGF but with very scarce data. Further research is needed to establish BDNF and NGF as suitable biomarkers for the disease.

The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.

The Zingiberaceae family possess various phenolic compounds that have significant systemic bioactivities in the brain, including in age-related neurodegenerative diseases. Neurotrophins are growth factors that protect neurons from oxidative stress, and dysregulation of the neurotrophic system may result in neurocognitive disease. Phenolic compounds from the Zingiberaceae family have been used in traditional and complementary medicine (TCM) to improve cognitive functions. These compounds may affect the expression of neurotrophic agents, but their underlying molecular mechanisms require further investigation. Therefore, the goal of this review is to determine the expression and functional roles of phenolic compounds from the Zingiberaceae family in brain disorders and age-related neurodegenerative disorders. While previous studies have proposed various mechanisms for the neuroprotective activity of these compounds, their precise mechanism of action remains complex and poorly understood. Despite some promising findings, there are still shortcomings in the therapeutic use of these herbs, and current interventions involving the Zingiberaceae family appear to be clinically insufficient. This article aims to summarize recent discoveries of phenolic compounds from several Zingiberaceae family members and their use as neuroprotectants and provide the first review of evidence-linked neuroprotective activity of bioactive ingredients from prominent members of the Zingiberaceae family.