Mature Nervous System Research Articles

A Promising Application of Injectable Hydrogels in Nerve Repair and Regeneration for Ischemic Stroke.

Ischemic stroke, a condition that often leads to severe nerve damage, induces complex pathological and physiological changes in nerve tissue. The mature central nervous system (CNS) lacks intrinsic regenerative capacity, resulting in a poor prognosis and long-term neurological impairments. There is no available therapy that can fully restore CNS functionality. However, the utilization of injectable hydrogels has emerged as a promising strategy for nerve repair and regeneration. Injectable hydrogels possess exceptional properties, such as biocompatibility, tunable mechanical properties, and the ability to provide a supportive environment for cell growth and tissue regeneration. Recently, various hydrogel-based tissue engineering approaches, including cell encapsulation, controlled release of therapeutic factors, and incorporation of bioactive molecules, have demonstrated great potential in the treatment of CNS injuries caused by ischemic stroke. This article aims to provide a comprehensive review of the application and development of injectable hydrogels for the treatment of ischemic stroke-induced CNS injuries, shedding light on their therapeutic prospects, challenges, recent advancements, and future directions. Additionally, it will discuss the underlying mechanisms involved in hydrogel-mediated nerve repair and regeneration, as well as the need for further preclinical and clinical studies to validate their efficacy and safety.

Neurological examination of healthy term infants at ages 6 and 10 weeks in Tshwane District.

Globally, there is a significant gap in detailed neurodevelopmental data for infants under 3 months, despite 6 weeks being identified a critical milestone for neuro-behavioural development. Normative values and optimal scores for healthy infants at 6 and 10 weeks postnatally are lacking in many settings. In South Africa, the statutory neurodevelopmental assessments at these ages exclude notable characteristics of central nervous system maturation and limit opportunities to collect data of early developmental progress. Our study aimed to assess developmental characteristics of healthy term infants aged 6 and 10 weeks using the Hammersmith Neonatal Neurological Examination (HNNE). A prospective longitudinal study was performed on 35 healthy term-born infants from low-risk pregnancies at 6 and 10 weeks' postnatal age in the Tshwane district. The statuses of infants' neurodevelopment in six domains were recorded using the HNNE. Optimality scores were derived from the raw scores of 34 items, using the 10th and 5th percentiles as cut-off points. Evidences of neurodevelopmental advancements, particularly in posture, muscle tone and visual behaviour between 6 and 10 weeks were illustrated, and total examination optimality scores of 29.5 in 91% and 31.5 in 94% of infants were recorded at 6 and 10 weeks, respectively. This article provides data on the neurodevelopment characteristics of infants at and between 6- and 10-weeks post term ages. The findings support the viewpoint to identify important milestone characteristics during early screening.

Maternal singing sustains preterm hospitalized newborns’ autonomic nervous system maturation: an RCT

BackgroundPremature birth is known to affect the newborn’s autonomic nervous system (ANS) maturation, with potential short and long-term impact on their neurobehavioral development. The purpose of the study was to investigate the effects of maternal directed singing and speaking on the preterm infants’ autonomic nervous system (ANS) maturation as measured by the heart rate variability (HRV) parameters.MethodsIn this multi-center randomized clinical trial, 30 stable preterm infants (m = 29,6 weeks of gestational age), without any abnormalities were randomized into an intervention (16) or a control group (14). HRV was measured weekly, for a total of 80 recordings during hospitalization, as well as before and after each session of singing or speaking.ResultsThe intervention group showed a significant increase of the percentage value of HRV power in the high frequency range when compared to the control group (p = 0.044). More specifically, the maternal singing significantly increased the high frequency power and decreased the low/high frequency power ratio (p = 0.037).ConclusionsThe preterm infant’s vagal activity significantly increased in the intervention group, potentially enhancing their ANS maturation. The effect is specifically evidenced in the singing condition.ImpactMaternal singing affects the autonomic nervous system maturation of preterm hospitalized newborns in the NICU.No previous studies investigated how early vocal parental intervention can affect preterm infants developement, throught their autonomic nervous system maturation.Early Vocal Contact as an early intervention involving parents has a positive impact on preterm infant’s development and it can be easily implemented in the care of preterm infants.Trial registrationNCT04759573, retrospectively registered, 17 February 2021.

Verification studies of tryptophan and kynurenine determination using HPLC and evaluation of the kynurenine pathway and neopterin levels in human colostrum samples.

Colostrum, the first breast fluid produced by mammals after giving birth, is followed by breast milk, which serves as the sole source of nutrients for breastfed newborns and infants. Tryptophan, an essential amino acid, plays a crucial role in the development and maturation of the central nervous system in infants. Tryptophan is primarily degraded through the kynurenine pathway. Owing to its sensitivity to dietary intake, immune-mediated tryptophan degradation is assessed by the kynurenine-to-tryptophan ratio, with a focus on one of the rate-limiting enzymes in the pathway. This study involved the validation of the simultaneous determination of tryptophan and kynurenine using HPLC. The validated method was then used to detect levels of tryptophan and kynurenine, as well as to calculate the kynurenine-to-tryptophan ratio in colostrum samples. Simultaneously, these results were compared with colostrum neopterin levels measured using commercial enzyme-linked immunosorbent assay kits. The mean levels for tryptophan, kynurenine, and neopterin were 17.3 ± 62.4 μM, 0.45 ± 0.03 μM, and 28.9 ± 2.6 nM, respectively. This study is among the few that have evaluated these parameters in colostrum samples. Neopterin levels secreted by the mammary gland were found not to be correlated with tryptophan degradation, a process influenced by the mother's nutritional status.

Sensory event-related potential morphology predicts age in premature infants

ObjectiveWe investigated whether sensory-evoked cortical potentials could be used to estimate the age of an infant. Such a model could be used to identify infants who deviate from normal neurodevelopment. MethodsInfants aged between 28- and 40-weeks post-menstrual age (PMA) (166 recording sessions in 96 infants) received trains of visual and tactile stimuli. Neurodynamic response functions for each stimulus were derived using principal component analysis and a machine learning model trained and validated to predict infant age. ResultsPMA could be predicted accurately from the magnitude of the evoked responses (training set mean absolute error and 95% confidence intervals: 1.41 [1.14; 1.74] weeks,p = 0.0001; test set mean absolute error: 1.55 [1.21; 1.95] weeks,p = 0.0002). Moreover, we show that their predicted age (their brain age) is correlated with a measure known to relate to maturity of the nervous system and is linked to long-term neurodevelopment. ConclusionsSensory-evoked potentials are predictive of age in premature infants and brain age deviations are related to biologically and clinically meaningful individual differences in nervous system maturation. SignificanceThis model could be used to detect abnormal development of infants’ response to sensory stimuli in their environment and may be predictive of neurodevelopmental outcome.

Conditional knockout of REST/NRSF in excitatory neurons reduces seizure susceptibility to chemical kindling.

The repressor element-1 silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is an epigenetic master regulator that plays a crucial role during nervous system development and maturation. REST function was originally described during development, where it determines neuronal phenotype. However, recent studies showed that REST participates in several processes in the adult brain, including neuronal plasticity and epileptogenesis. In this regard, the relationships between REST and epilepsy are still controversial and need further investigation. As forebrain excitatory neurons are the common final pathway of seizure susceptibility, we investigated the role of REST in epilepsy by inducing REST conditional knockout (REST-cKO) specifically in excitatory neurons of the hippocampus. To target the excitatory neuronal population, we cloned the calcium/calmodulin-dependent protein kinase IIα minimal promoter upstream of Cre recombinase. After assessing the specificity of the promoter's expression, the transgenes were packaged in an engineered adeno-associated virus able to cross the blood-brain and blood-cerebrospinal fluid barriers and delivered in the lateral ventricles of 2-month-old RESTflox/flox mice to characterize, after 1 month, the cognitive phenotype and the seizure propensity. We show that REST-cKO mice display lower levels of anxiety in the light-dark test with respect to control mice but have unaltered motor, social, and cognitive profiles. The evaluation of the susceptibility to epileptic seizures showed that REST-cKO mice are more resistant to pentylenetetrazole-induced kindling but not to seizures induced by a single administration of the convulsant and show higher survival rates. Overall, these data suggest that the absence of REST in forebrain excitatory neurons decreases seizure susceptibility, pointing to a pro-epileptogenic role of the transcriptional repressor under conditions of pathological excitation/inhibition imbalance.

Inflammatory Mediators of Axon Regeneration in the Central and Peripheral Nervous Systems.

Although most pathways in the mature central nervous system cannot regenerate when injured, research beginning in the late 20th century has led to discoveries that may help reverse this situation. Here, we highlight research in recent years from our laboratory identifying oncomodulin (Ocm), stromal cell-derived factor (SDF)-1, and chemokine CCL5 as growth factors expressed by cells of the innate immune system that promote axon regeneration in the injured optic nerve and elsewhere in the central and peripheral nervous systems. We also review the role of ArmC10, a newly discovered Ocm receptor, in mediating many of these effects, and the synergy between inflammation-derived growth factors and complementary strategies to promote regeneration, including deleting genes encoding cell-intrinsic suppressors of axon growth, manipulating transcription factors that suppress or promote the expression of growth-related genes, and manipulating cell-extrinsic suppressors of axon growth. In some cases, combinatorial strategies have led to unprecedented levels of nerve regeneration. The identification of some similar mechanisms in human neurons offers hope that key discoveries made in animal models may eventually lead to treatments to improve outcomes after neurological damage in patients.

CRYAB plays a role in terminating the presence of pro-inflammatory macrophages in the older, injured mouse peripheral nervous system

Evidence indicates that dysfunction of older Schwann cells and macrophages contributes to poor regeneration of more mature peripheral nervous system (PNS) neurons after damage. Since the underlying molecular factors are largely unknown, we investigated if CRYAB, a small heat shock protein that is expressed by Schwann cells and axons and whose expression declines with age, impacts prominent deficits in the injured, older PNS including down-regulation of cholesterol biosynthesis enzyme genes, Schwann cell dysfunction, and macrophage persistence. Following sciatic nerve transection injury in 3- and 12-month-old wildtype and CRYAB knockout mice, we found by bulk RNA sequencing and RT-PCR, that while gene expression of cholesterol biosynthesis enzymes is markedly dysregulated in the aging, injured PNS, CRYAB is not involved. However, immunohistochemical staining of crushed sciatic nerves revealed that more macrophages of the pro-inflammatory but not immunosuppressive phenotype persisted in damaged 12-month-old knockout nerves. These pro-inflammatory macrophages were more efficient at engulfing myelin debris. CRYAB thus appears to play a role in resolving pro-inflammatory macrophage responses after damage to the older PNS.

Pilot study shows skin-to-skin care with parents improves heart rate variability in preterm infants in the neonatal intensive care unit.

Skin-to-skin care in the newborn intensive care unit typically lasts for short periods of time and enhances breastfeeding, attachment, and parental self-esteem. Heart rate variability (HRV) increases with gestational age and is a measure of maturation of parasympathetic vs. sympathetic autonomic nervous system activity. HRV measurements may be useful in capturing changes in autonomic regulation in response to skin-to-skin care. To analyze the effects of skin-to-skin care on HRV in preterm infants receiving respiratory support. We hypothesized that skin-to-skin care would result in a more mature pattern of parasympathetic activity. In this prospective crossover study, infants <30 weeks' gestation and 1-6 weeks postnatal age had HRV recorded for 30 min before, during, and after skin-to-skin care sessions. HRV characteristics analyzed included the standard deviation of the normal-to-normal interval (SDNN), the root mean squared of successive differences of normal-to-normal intervals (RMSSD), and the standard deviation of decelerations (SDDec). 10 infants between 25 5/7-29 6/7 weeks gestational age and 7-41 days postnatal age completed 22 sessions while receiving respiratory support (positive pressure ventilation or nasal cannula oxygen). Two measures of HRV (SDNN and RMSSD) were significantly decreased by the end of the skin-to-skin sessions, compared to pre-session values. SDNN decreased from a median of 10.44 ms before the session to 6.70 ms after being placed back in bed (p < 0.05), with RMSSD decreasing from a median of 6.80 ms before the session to 4.32 ms while being held at the end of 30 min (p < 0.05). Skin-to-skin care with a parent resulted in a more mature autonomic nervous system pattern in preterm infants receiving respiratory support, suggesting physiologic benefit for the infant. No adverse events were seen during any session.

Contemporary Understanding of the Central Autonomic Nervous System in Fetal-Neonatal Transition

THE CRITICAL ROLE OF THE CENTRAL AUTONOMIC NERVOUS SYSTEM IN FETAL-NEONATAL TRANSITION: Sarah B. Mulkey, Adre dú Plessis Seminars in Pediatric Neurology Volume 28, December 2018, Pages 29-37 The objective of this article is to understand the complex role of the central autonomic nervous system in normal and complicated fetal-neonatal transition and how autonomic nervous system dysfunction can lead to brain injury. The central autonomic nervous system supports coordinated fetal transitional cardiovascular, respiratory, and endocrine responses to provide safe transition of the fetus at delivery. Fetal and maternal medical and environmental exposures can disrupt normal maturation of the autonomic nervous system in utero, cause dysfunction, and complicate fetal-neonatal transition. Brain injury may both be caused by autonomic nervous system failure and contribute directly to autonomic nervous system dysfunction in the fetus and newborn. The central autonomic nervous system has multiple roles in supporting transition of the fetus. Future studies should aim to improve real-time monitoring of fetal autonomic nervous system function and in supporting typical autonomic nervous system development even under complicated conditions.

Plasticity and genetic effects contribute to different axes of neural divergence in a community of mimetic Heliconius butterflies.

Changes in ecological preference, often driven by spatial and temporal variation in resource distribution, can expose populations to environments with divergent information content. This can lead to adaptive changes in the degree to which individuals invest in sensory systems and downstream processes, to optimize behavioural performance in different contexts. At the same time, environmental conditions can produce plastic responses in nervous system development and maturation, providing an alternative route to integrating neural and ecological variation. Here, we explore how these two processes play out across a community of Heliconius butterflies. Heliconius communities exhibit multiple Mullerian mimicry rings, associated with habitat partitioning across environmental gradients. These environmental differences have previously been linked to heritable divergence in brain morphology in parapatric species pairs. They also exhibit a unique dietary adaptation, known as pollen feeding, that relies heavily on learning foraging routes, or trap-lines, between resources, which implies an important environmental influence on behavioural development. By comparing brain morphology across 133 wild-caught and insectary-reared individuals from seven Heliconius species, we find strong evidence for interspecific variation in patterns of neural investment. These largely fall into two distinct patterns of variation; first, we find consistent patterns of divergence in the size of visual brain components across both wild and insectary-reared individuals, suggesting genetically encoded divergence in the visual pathway. Second, we find interspecific differences in mushroom body size, a central component of learning and memory systems, but only among wild caught individuals. The lack of this effect in common-garden individuals suggests an extensive role for developmental plasticity in interspecific variation in the wild. Finally, we illustrate the impact of relatively small-scale spatial effects on mushroom body plasticity by performing experiments altering the cage size and structure experienced by individual H. hecale. Our data provide a comprehensive survey of community level variation in brain structure, and demonstrate that genetic effects and developmental plasticity contribute to different axes of interspecific neural variation.

A new microfluidic model to study dendritic remodeling and mitochondrial dynamics during axonal regeneration of adult zebrafish retinal neurons.

Unlike mammals, adult zebrafish are able to fully regenerate axons and functionally recover from neuronal damage in the mature central nervous system (CNS). Decades of research have tried to identify the mechanisms behind their spontaneous regenerative capacity, but the exact underlying pathways and molecular drivers remain to be fully elucidated. By studying optic nerve injury-induced axonal regrowth of adult zebrafish retinal ganglion cells (RGCs), we previously reported transient dendritic shrinkage and changes in the distribution and morphology of mitochondria in the different neuronal compartments throughout the regenerative process. These data suggest that dendrite remodeling and temporary changes in mitochondrial dynamics contribute to effective axonal and dendritic repair upon optic nerve injury. To further elucidate these interactions, we here present a novel adult zebrafish microfluidic model in which we can demonstrate compartment-specific alterations in resource allocation in real-time at single neuron level. First, we developed a pioneering method that enables to isolate and culture adult zebrafish retinal neurons in a microfluidic setup. Notably, with this protocol, we report on a long-term adult primary neuronal culture with a high number of surviving and spontaneously outgrowing mature neurons, which was thus far only very limitedly described in literature. By performing time-lapse live cell imaging and kymographic analyses in this setup, we can explore changes in dendritic remodeling and mitochondrial motility during spontaneous axonal regeneration. This innovative model system will enable to discover how redirecting intraneuronal energy resources supports successful regeneration in the adult zebrafish CNS, and might facilitate the discovery of new therapeutic targets to promote neuronal repair in humans.

Dedicated macrophages organize and maintain the enteric nervous system.

Correct development and maturation of the enteric nervous system (ENS) is critical for survival1. At birth, the ENS is immature and requires considerable refinement to exert its functions in adulthood2. Here we demonstrate that resident macrophages of the muscularis externa (MMϕ) refine the ENS early in life by pruning synapses and phagocytosing enteric neurons. Depletion of MMϕ before weaning disrupts this process and results in abnormal intestinal transit. After weaning, MMϕ continue to interact closely with the ENS and acquire a neurosupportive phenotype. The latter is instructed by transforming growth factor-β produced by the ENS; depletion of the ENS and disruption of transforming growth factor-β signalling result in a decrease in neuron-associated MMϕ associated with loss of enteric neurons and altered intestinal transit. These findings introduce a new reciprocal cell-cell communication responsible for maintenance of the ENS and indicate that the ENS, similarly to the brain, is shaped and maintained by a dedicated population of resident macrophages that adapts its phenotype and transcriptome to the timely needs of the ENS niche.

Plexina4 and cell survival in the developing zebrafish hindbrain.

Growth factors are important in the developing and mature nervous system to support the survival of neurons. Developmental signaling molecules are known for their roles in controlling neurogenesis and neural circuit formation. Whether or not these molecules also have roles in cell survival in the developing nervous system is poorly understood. Plexins are a family of transmembrane receptors that bind Semaphorin ligands and are known to function in the guidance of developing axons and blood vessels. In embryonic zebrafish, plexina4 is expressed widely in the brain, becoming largely restricted to the hindbrain as neurogenesis and differentiation proceed. Apoptosis is increased in the embryonic hindbrain of a plexina4ca307/ca307 CRISPR mutant. Based on the literature, we tested the secreted heat shock protein, Clusterin, as a candidate ligand to mediate cell survival through Plexina4. clusterin is expressed by the floor plate of the embryonic zebrafish hindbrain, in proximity to plexina4-expressing hindbrain cells. Morpholino-mediated knockdown of Clusterin increases cell apoptosis in the hindbrain, with additional cell death observed in epistasis experiments where Clusterin is knocked down in a plexina4 mutant background. Our data suggest that Plexina4 promotes cell survival in the developing zebrafish hindbrain, likely through a pathway independent of Clusterin.

Brain-derived neurotrophic factor: Its role in energy balance and cancer cachexia

Brain-derived neurotrophic factor (BDNF) plays an important role in the development of the central and peripheral nervous system during embryogenesis. In the mature central nervous system, BDNF is required for the maintenance and enhancement of synaptic transmissions and the survival of neurons. Particularly, it is involved in the modulation of neurocircuits that control energy balance through food intake, energy expenditure, and locomotion. Regulation of BDNF in the central nervous system is complex and environmental factors affect its expression in murine models which may reflect to phenotype dramatically. Furthermore, BDNF and its high-affinity receptor tropomyosin receptor kinase B (TrkB), as well as pan-neurotrophin receptor (p75NTR) is expressed in peripheral tissues in adulthood and their signaling is associated with regulation of energy balance. BDNF/TrkB signaling is exploited by cancer cells as well and BDNF expression is increased in tumors. Intriguingly, previously demonstrated roles of BDNF in regulation of food intake, adipose tissue and muscle overlap with derangements observed in cancer cachexia. However, data about the involvement of BDNF in cachectic cancer patients and murine models are scarce and inconclusive. In the future, knock-in and/or knock-out experiments with murine cancer models could be helpful to explore potential new roles for BDNF in the development of cancer cachexia.

Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice

Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes according to the age of infection and sex in mice: neonatally infected animals presented an increase in PPI and delayed startle latency. However, adult-infected male mice presented lower startle amplitude, while a PPI impairment was observed 14 days after infection in both sexes. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the startle reflex testing in ZIKV-exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.

Biological functions of the Olig gene family in brain cancer and therapeutic targeting.

The Olig genes encode members of the basic helix-loop-helix (bHLH) family of transcription factors. Olig1, Olig2, and Olig3 are expressed in both the developing and mature central nervous system (CNS) and regulate cellular specification and differentiation. Over the past decade extensive studies have established functional roles of Olig1 and Olig2 in development as well as in cancer. Olig2 overexpression drives glioma proliferation and resistance to radiation and chemotherapy. In this review, we summarize the biological functions of the Olig family in brain cancer and how targeting Olig family genes may have therapeutic benefit.

Higher Availability of Long-Chain Monounsaturated Fatty Acids in Preterm than in Full-Term Human Milk.

While the role of n-3 and n-6 long-chain polyunsaturated fatty acids (LCPUFAs) in the maturation of the infantile nervous system is extensively studied and relatively well-characterized, data on the potential developmental importance of the n-9 long-chain monounsaturated fatty acid (LCMUFA), nervonic acid (NA, C24:1n-9) are scarce and ambiguous. Therefore, the aim of the present study was to reanalyze our available data on the contribution of NA and its LCMUFA precursors, gondoic acid (C20:1n-9) and erucic acid (EA, C22:1n-9) to the fatty acid composition of human milk (HM) during the first month of lactation in mothers of both preterm (PT) and full-term (FT) infants. HM samples were obtained daily during the first week of lactation, and then on the 14th, 21st, and 28th days. Values of the LCMUFAs, C20:1n-9, EA, and NA were significantly higher in colostrum than in transient and mature HM. Consequently, there were highly significant inverse associations between LCMUFA values and the duration of lactation. Moreover, C20:1n-9, EA, and NA values were monotonously, considerably, and at many timepoints significantly higher in PT than in FT HM samples. By the 28th day of lactation, summarized LCMUFA values in PT HM samples declined to the level measured in FT HM samples on the first day of lactation; however, EA and NA values were still significantly higher in PT than in FT HM on the 28th day. Significantly higher availability of LCMUFAs in PT than in FT HM underpins the potential biological role of this hitherto somewhat neglected group of fatty acids.

Comparison of spatiotemporal gait parameters and their variability in typically developing children aged 2, 3, and 6 years.

Independent walking is an important milestone in a child's development. The maturation of central nervous system, changes in body proportions, spatiotemporal parameters of gait and their variability change are dependent on age. The first aim of this study was to compare non-normalized and normalized spatiotemporal parameters and their variability in children. The second aim was to determine which spatiotemporal parameters are most affected by aging. Data from 64 typically developing children (age: 2.0-6.9 years), who walked at a self-selected speed along a 10m walkway, were collected with a motion capture system. Spatiotemporal parameters were normalized based on leg length. The main effect of the non-normalized walking speed revealed a moderate effect size (ES = 0.72) comparing 2- and 3-years-old, a large effect size comparing 2- and 6-years-old (ES = 1.77), and a large ES comparing 3- and 6-years-old (ES = 1.22). The normalized stride width parameter showed a statistically significant difference with large effect size between 2 vs 3 (ES = 1.00), 2 vs 6 (ES = 3.17), and 3 vs 6 (ES = 1.96). A statistically significant decrease in intra-individual gait variability with increasing age was observed in all parameters except for stride width. The variability of stride width may serve as a parameter in 2-year-olds to assess deviations from typically developing children. The assessment of effect size could be a useful indicator for clinical practice.

Identification of potential inhibitors of tropomyosin receptor kinase B targeting CNS-related disorders and cancers

Tropomyosin receptor kinase B (TrkB), also known as neurotrophic tyrosine kinase receptor type 2 (NTRK2), is a protein that belongs to the family of receptor tyrosine kinases (RTKs). NTRK2 plays a crucial role in regulating the development and maturation of the central nervous system (CNS) and peripheral nervous system (PNS). Elevated TrkB expression levels observed in different pathological conditions make it a potential target for therapeutic interventions against neurological disorders, including depression, anxiety, Alzheimer’s disease, Parkinson’s disease, and certain types of cancer. Targeting TrkB using small molecule inhibitors is a promising strategy for the treatment of a variety of neurological disorders. In this research, a systematic virtual screening was carried out on phytoconstituents found in the IMPPAT library to identify compounds potentially inhibiting TrkB. The retrieved compounds from the IMPPAT library were first filtered using Lipinski’s rule of five. The compounds were then sorted based on their docking score and ligand efficiency. In addition, PAINS, ADMET, and PASS evaluations were carried out for selecting drug-like compounds. Finally, in interaction analysis, we found two phytoconstituents, Wedelolactone and 3,8-dihydroxy-1-methylanthraquinone-2-carboxylic acid (DMCA), which possessed considerable docking scores and specificity on the TrkB ATP-binding pocket. The selected compounds were further assessed employing molecular dynamics (MD) simulations and essential dynamics. The results revealed that the elucidated compounds bind well with the TrkB binding pocket and lead to fewer conformations fluctuations. This study highlighted using phytoconstituents, Wedelolactone and DMCA as starting leads in developing novel TrkB inhibitors. Communicated by Ramaswamy H. Sarma