Axon Diameter Research Articles

A new open, high-resolution, multishell, diffusion-weighted imaging dataset of the living squirrel monkey

Although very well adapted to brain study, Magnetic Resonance Imaging (MRI) remains limited by the facilities and capabilities required to acquire data, especially for non-human primates. Addressing the data gaps resulting from these limitations requires making data more accessible and open. In contempt of the regular use of Saimiri sciureus in neuroscience research, in vivo diffusion has yet to be openly available for this species. Here we built and made openly available a unique new resource consisting of a high-resolution, multishell diffusion-weighted dataset in the anesthetized Saimiri sciureus. The data were acquired on 11 individuals with an 11.7 T MRI scanner (isotropic resolution of 400 µm3). This paper presents an overview of our dataset and illustrates some of its possible use through example analyses. To assess the quality of our data, we analyzed long-range connections (whole-brain tractography), microstructure (Neurite Orientation Dispersion and Density Imaging), and axon diameter in the corpus callosum (ActiveAx). Constituting an essential new resource for primate evolution studies, all data are openly available.

OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.

OPA1 Dominant Optic Atrophy: Pathogenesis and Therapeutic Targets.

The role of Gel-Ppy-modified nerve conduit on the repair of sciatic nerve defect in rat model.

The serious clinical challenge of peripheral nerve injury (PNI) is nerve regeneration. Nerve conduit represents a promising strategy to contribute to nerve regeneration by bridging injured nerve gaps. However, due to a unique microenvironment of nerve tissue, autologous nerves have not been substituted by nerve conduit. Nerve regeneration after nerve conduit implantation depends on many factors, such as conductivity and biocompatibility. Therefore, Gelatin (Gel) with biocompatibility and polypyrrole (Ppy) with conductivity is highly concerned. In this paper, Gel-Ppy modified nerve conduit was fabricated with great biocompatibility and conductivity to evaluate its properties of enhancing nerve regeneration in vivo and in vitro. The proliferation of Schwann cells on Gel-Ppy modified nerve conduit was remarkably increased. Consistent with in vitro results, the Gel-Ppy nerve conduit could contribute to the regeneration of Schwann cell in vivo. The axon diameters and myelin sheath thickness were also enhanced, resulting in the amelioration of muscle atrophy, nerve conduction, and motor function recovery. To explain this interesting phenomenon, western blot results indicated that the Gel-Ppy conduit facilitated nerve regeneration via upregulating the Rap1 pathway to induce neurite outgrowth. Therefore, the above results demonstrated that Gel-Ppy modified nerve conduit could provide an acceptable microenvironment for nerve regeneration and be popularized as a novel therapeutic strategy of PNI.

The Effect of Acetyl-L-Carnitine (ALCAR) on Peripheral Nerve Regeneration in Animal Models: A Systematic Review.

Peripheral neuropathies caused by the peripheral nervous system (PNS) damage can occur due to trauma and other disorders. They present as altered sensation, weakness, autonomic symptoms, and debilitating pain syndrome with a wide range of clinical signs. Acetyl-L-Carnitine (ALCAR) is a biological compound with essential roles in mitochondrial oxidative metabolism and anti-oxidant effects that protects mitochondria from oxidative damage and inhibits apoptosis caused by mitochondrial damage. This study is a systematic review and meta-analysis of the effects of ALCAR on peripheral nerve injuries. This review examines studies on treating traumatic peripheral neuropathies in which ALCAR is administered to rats with sciatic nerve injury with an appropriate control group. The articles were divided based on the mode of ALCAR administration. If one method was used in more than one article, their results were entered in the "Revman5.4" software and were meta-analyzed. Studies were selected from 1994 to 2018 on rats with varying physical injuries to their sciatic nerves. In one study, ALCAR was provided to rats in their drinking water, while in other studies, ALCAR was injected intra-peritoneally. Different mechanisms of ALCAR actions have been suggested in this study, but the underpinnings of the neuroprotective effects of ALCAR are still unclear. Further studies are mandatory to clarify the actual mechanisms of the neuroprotective activity of ALCAR. Based on the results of existing studies, ALCAR effectively increases the tolerance threshold of thermal and mechanical stimuli, reduces latency, and reduces apoptosis; finally, adjusting the dose and duration of administration may increase the dose and duration axon diameter.

A Method for In-Vivo Mapping of Axonal Diameter Distributions in the Human Brain Using Diffusion-Based Axonal Spectrum Imaging (AxSI).

In this paper we demonstrate a generalized and simplified pipeline called axonal spectrum imaging (AxSI) for in-vivo estimation of axonal characteristics in the human brain. Whole-brain estimation of the axon diameter, in-vivo and non-invasively, across all fiber systems will allow exploring uncharted aspects of brain structure and function relations with emphasis on connectivity and connectome analysis. While axon diameter mapping is important in and of itself, its correlation with conduction velocity will allow, for the first time, the explorations of information transfer mechanisms within the brain. We demonstrate various well-known aspects of axonal morphometry (e.g., the corpus callosum axon diameter variation) as well as other aspects that are less explored (e.g., axon diameter-based separation of the superior longitudinal fasciculus into segments). Moreover, we have created an MNI based mean axon diameter map over the entire brain for a large cohort of subjects providing the reference basis for future studies exploring relation between axon properties, its connectome representation, and other functional and behavioral aspects of the brain.

The Value of Various Post-Processing Modalities of Diffusion Weighted Imaging in the Detection of Multiple Sclerosis

Diffusion tensor imaging (DTI) showed its adequacy in evaluating the normal-appearing white matter (NAWM) and lesions in the brain that are difficult to evaluate with routine clinical magnetic resonance imaging (MRI) in multiple sclerosis (MS). Recently, MRI systems have been developed with regard to software and hardware, leading to different proposed diffusion analysis methods such as diffusion tensor imaging, q-space imaging, diffusional kurtosis imaging, neurite orientation dispersion and density imaging, and axonal diameter measurement. These methods have the ability to better detect in vivo microstructural changes in the brain than DTI. These different analysis modalities could provide supplementary inputs for MS disease characterization and help in monitoring the disease's progression as well as treatment efficacy. This paper reviews some of the recent diffusion MRI methods used for the assessment of MS in vivo.

Boosting neuregulin 1 type-III expression hastens SMA motor axon maturation

Intercellular communication between axons and Schwann cells is critical for attaining the complex morphological steps necessary for axon maturation. In the early onset motor neuron disease spinal muscular atrophy (SMA), many motor axons are not ensheathed by Schwann cells nor grow sufficiently in radial diameter to become myelinated. These developmentally arrested motor axons are dysfunctional and vulnerable to rapid degeneration, limiting efficacy of current SMA therapeutics. We hypothesized that accelerating SMA motor axon maturation would improve their function and reduce disease features. A principle regulator of peripheral axon development is neuregulin 1 type III (NRG1-III). Expressed on axon surfaces, it interacts with Schwann cell receptors to mediate axon ensheathment and myelination. We examined NRG1 mRNA and protein expression levels in human and mouse SMA tissues and observed reduced expression in SMA spinal cord and in ventral, but not dorsal root axons. To determine the impact of neuronal NRG1-III overexpression on SMA motor axon development, we bred NRG1-III overexpressing mice to SMA∆7 mice. Neonatally, elevated NRG1-III expression increased SMA ventral root size as well as axon segregation, diameter, and myelination resulting in improved motor axon conduction velocities. NRG1-III was not able to prevent distal axonal degeneration nor improve axon electrophysiology, motor behavior, or survival of older mice. Together these findings demonstrate that early SMA motor axon developmental impairments can be ameliorated by a molecular strategy independent of SMN replacement providing hope for future SMA combinatorial therapeutic approaches.

VEGFA-modified DPSCs combined with LC-YE-PLGA NGCs promote facial nerve injury repair in rats

ObjectiveThe aim of this research was to investigate the effect of vascular endothelial growth factor A (VEGFA)-overexpressing rat dental pulp stem cells (rDPSCs) combined with laminin-coated and yarn-encapsulated poly(l-lactide-co-glycolide) (PLGA) nerve guidance conduit (LC-YE-PLGA NGC) in repairing 10 mm facial nerve injury in rats. Study DesignrDPSCs isolated from rat mandibular central incisor were cultured and identified in vitro and further transfected with the lentiviral vectors (Lv-VEGFA). To investigate the role and mechanisms of VEGFA in neurogenic differentiation in vitro, semaxanib (SU5416), Cell Counting Kit-8 (CCK-8), real-time quantitative polymerase chain reaction (qPCR) and Western blotting were performed. Ten-millimeter facial nerve defect models in rats were established and bridged by LC-YE-PLGA NGCs. The repair effects were detected by transmission electron microscopy (TEM), compound muscle action potential (CMAP), immunohistochemistry and immunofluorescence. ResultsExtracted cells exhibited spindle-shaped morphology, presented typical markers (CD44+CD90+CD34−CD45−), and presented multidirectional differentiation potential. The DPSCs with VEGFA overexpression were constructed successfully. VEGFA enhanced the proliferation and neural differentiation ability of rDPSCs, and the expression of neuron-specific enolase (NSE) and βIII-tubulin was increased. However, these trends were reversed with the addition of SU5416. This suggests that VEGFA mediates the above effects mainly through vascular endothelial growth factor receptor 2 (VEGFR2) binding. The LC-YE-NGC basically meet the requirements of facial nerve repair. For the in vivo experiment, the CMAP latency period was shorter in DPSCS-VEGFA-NGC group in comparison with other experimental groups, while the amplitude was increased. Such functional recovery correlated well with an increase in histological improvement. Further study suggested that VEGFA-modified DPSCs could increase the myelin number, thickness and axon diameter of facial nerve. NSE, βIII-tubulin and S100 fluorescence intensity and immunohistochemical staining intensity were significantly enhanced. ConclusionVEGFA-modified rDPSCs combined with LC-YE-PLGA NGCs have certain advantages in the growth and functional recovery of facial nerves in rats.

Meta-analysis of the normal diffusion tensor imaging values of the peripheral nerves in the upper limb

Peripheral neuropathy affects 1 in 10 adults over the age of 40 years. Given the absence of a reliable diagnostic test for peripheral neuropathy, there has been a surge of research into diffusion tensor imaging (DTI) because it characterises nerve microstructure and provides reproducible proxy measures of myelination, axon diameter, fibre density and organisation. Before researchers and clinicians can reliably use diffusion tensor imaging to assess the ‘health’ of the major nerves of the upper limb, we must understand the “normal” range of values and how they vary with experimental conditions. We searched PubMed, Embase, medRxiv and bioRxiv for studies which reported the findings of DTI of the upper limb in healthy adults. Four review authors independently triple extracted data. Using the meta suite of Stata 17, we estimated the normal fractional anisotropy (FA) and diffusivity (mean, MD; radial, RD; axial AD) values of the median, radial and ulnar nerve in the arm, elbow and forearm. Using meta-regression, we explored how DTI metrics varied with age and experimental conditions. We included 20 studies reporting data from 391 limbs, belonging to 346 adults (189 males and 154 females, ~ 1.2 M:1F) of mean age 34 years (median 31, range 20–80). In the arm, there was no difference in the FA (pooled mean 0.59 mm2/s [95% CI 0.57, 0.62]; I2 98%) or MD (pooled mean 1.13 × 10–3 mm2/s [95% CI 1.08, 1.18]; I2 99%) of the median, radial and ulnar nerves. Around the elbow, the ulnar nerve had a 12% lower FA than the median and radial nerves (95% CI − 0.25, 0.00) and significantly higher MD, RD and AD. In the forearm, the FA (pooled mean 0.55 [95% CI 0.59, 0.64]; I2 96%) and MD (pooled mean 1.03 × 10–3 mm2/s [95% CI 0.94, 1.12]; I2 99%) of the three nerves were similar. Multivariable meta regression showed that the b-value, TE, TR, spatial resolution and age of the subject were clinically important moderators of DTI parameters in peripheral nerves. We show that subject age, as well as the b-value, TE, TR and spatial resolution are important moderators of DTI metrics from healthy nerves in the adult upper limb. The normal ranges shown here may inform future clinical and research studies.

Modeling extracellular stimulation of retinal ganglion cells: theoretical and practical aspects

Objective. Retinal prostheses use electric current to activate inner retinal neurons, providing artificial vision for blind people. Epiretinal stimulation primarily targets retinal ganglion cells (RGCs), which can be modeled with cable equations. Computational models provide a tool to investigate the mechanisms of retinal activation, and improve stimulation paradigms. However, documentation of RGC model structure and parameters is limited, and model implementation can influence model predictions. Approach. We created a functional guide for building a mammalian RGC multi-compartment cable model and applying extracellular stimuli. Next, we investigated how the neuron’s three-dimensional shape will influence model predictions. Finally, we tested several strategies to maximize computational efficiency. Main results. We conducted sensitivity analyses to examine how dendrite representation, axon trajectory, and axon diameter influence membrane dynamics and corresponding activation thresholds. We optimized the spatial and temporal discretization of our multi-compartment cable model. We also implemented several simplified threshold prediction theories based on activating function, but these did not match the prediction accuracy achieved by the cable equations. Significance. Through this work, we provide practical guidance for modeling the extracellular stimulation of RGCs to produce reliable and meaningful predictions. Robust computational models lay the groundwork for improving the performance of retinal prostheses.

Artificial PGA/Collagen-based Bilayer Conduit in Short Gap Interposition Setting Provides Comparable Regenerative Potential to Direct Suture.

Sixty-six female Lewis rats were randomly divided into the sham group (n = 13); no reconstruction (no-recon) group (n = 13; rat model with 10 mm sciatic nerve defect); direct group (n = 20; rat sciatic nerve injury directly connected by 10-0 Nylon); and SGI group (n = 20; sciatic nerve injury repaired using 5-mm Nerbridge). Motor function and histological recovery were evaluated. The sciatic nerve and gastrocnemius muscle were harvested for quantification of the degree of nerve regeneration and muscle atrophy. The SGI and direct groups achieved equal recovery in both functional and histological outcomes. At weeks 3 and 8 postsurgery, there was a significant improvement in the sciatic functional index of the SGI group when compared with that of the no-recon group (P < 0.05). Furthermore, the direct and SGI groups had less muscle atrophy at 4 and 8 weeks postsurgery compared with the no-recon group (P < 0.05). The axon density and diameter at the distal site in the SGI group were significantly higher than that in the no-recon group and comparable to that in the direct and sham groups. An artificial nerve conduit has equal potential as direct suture in motor nerve reconstruction when used in the SGI setting.

Drug repositioning: diacerein as a new therapeutic approach in a mice model of sciatic nerve injury.

Peripheral nerve injuries negatively impact the quality of life of patients, with no effective treatment available that accelerates sensorimotor recovery and promotes functional improvement and pain relief. The aim of this study was to evaluate the effects of diacerein (DIA) in an experimental mice model of sciatic nerve crush. In this study, male Swiss mice were used, randomly separated into six groups as follows: FO (false-operated + vehicle); FO + DIA (false-operated + diacerein 30mg/kg); SNI (sciatic nerve injury + vehicle); SNI + DIA in doses of 3, 10 and 30mg/kg (sciatic nerve injury + treatment with diacerein in doses of 3-30mg/kg). DIA or vehicle was administered 24h after the surgical procedure, intragastrically, twice a day. The lesion of the right sciatic nerve was generated by crush. We found that the treatment of animals with DIA accelerated sensorimotor recovery of the animal. In addition, animals in the sciatic nerve injury + vehicle (SNI) group showed hopelessness, anhedonia, and lack of well-being, which were significantly inhibited by DIA treatment. The SNI group showed a reduction in the diameters of nerve fibers, axons, and myelin sheaths, while DIA treatment recovered all these parameters. In addition, the treatment of animals with DIA prevented an increase the levels of interleukin (IL)-1β and a reduction in the levels of the brain-derived growth factor (BDNF). Treatment with DIA reduces hypersensitivity and depression like behaviors in animals. Furthermore, DIA promotes functional recovery and regulates IL-1β and BDNF concentrations.

Modulation of Schwann cell homeostasis by the BAP1 deubiquitinase.

Schwann cell programming during myelination involves transcriptional networks that activate gene expression but also repress genes that are active in neural crest/embryonic differentiation of Schwann cells. We previously found that a Schwann cell-specific deletion of the EED subunit of the Polycomb Repressive Complex (PRC2) led to inappropriate activation of many such genes. Moreover, some of these genes become re-activated in the pro-regenerative response of Schwann cells to nerve injury, and we found premature activation of the nerve injury program in a Schwann cell-specific knockout of Eed. Polycomb-associated histone modifications include H3K27 trimethylation formed by PRC2 and H2AK119 monoubiquitination (H2AK119ub1), deposited by Polycomb repressive complex 1 (PRC1). We recently found dynamic regulation of H2AK119ub1 in Schwann cell genes after injury. Therefore, we hypothesized that H2AK119 deubiquitination modulates the dynamic polycomb repression of genes involved in Schwann cell maturation. To determine the role of H2AK119 deubiquitination, we generated a Schwann cell-specific knockout of the H2AK119 deubiquitinase Bap1 (BRCA1-associated protein). We found that loss of Bap1 causes tomacula formation, decreased axon diameters and eventual loss of myelinated axons. The gene expression changes are accompanied by redistribution of H2AK119ub1 and H3K27me3 modifications to extragenic sites throughout the genome. BAP1 interacts with OGT in the PR-DUB complex, and our data suggest that the PR-DUB complex plays a multifunctional role in repression of the injury program. Overall, our results indicate Bap1 is required to restrict the spread of polycomb-associated histone modifications in Schwann cells and to promote myelin homeostasis in peripheral nerve.

Secondary Degeneration Impairs Myelin Ultrastructural Development in Adulthood following Adolescent Neurotrauma in the Rat Optic Nerve

Adolescence is a critical period of postnatal development characterized by social, emotional, and cognitive changes. These changes are increasingly understood to depend on white matter development. White matter is highly vulnerable to the effects of injury, including secondary degeneration in regions adjacent to the primary injury site which alters the myelin ultrastructure. However, the impact of such alterations on adolescent white matter maturation is yet to be investigated. To address this, female piebald-virol-glaxo rats underwent partial transection of the optic nerve during early adolescence (postnatal day (PND) 56) with tissue collection two weeks (PND 70) or three months later (PND 140). Axons and myelin in the transmission electron micrographs of tissue adjacent to the injury were classified and measured based on the appearance of the myelin laminae. Injury in adolescence impaired the myelin structure in adulthood, resulting in a lower percentage of axons with compact myelin and a higher percentage of axons with severe myelin decompaction. Myelin thickness did not increase as expected into adulthood after injury and the relationship between the axon diameter and myelin thickness in adulthood was altered. Notably, dysmyelination was not observed 2 weeks postinjury. In conclusion, injury in adolescence altered the developmental trajectory, resulting in impaired myelin maturation when assessed at the ultrastructural level in adulthood.

Temporal Diffusion Ratio (TDR) for imaging restricted diffusion: Optimisation and pre-clinical demonstration

Temporal Diffusion Ratio (TDR) is a recently proposed dMRI technique (Dell'Acqua et al., proc. ISMRM 2019) which provides contrast between areas with restricted diffusion and areas either without restricted diffusion or with length scales too small for characterisation. Hence, it has a potential for informing on pore sizes, in particular the presence of large axon diameters or other cellular structures. TDR employs the signal from two dMRI acquisitions obtained with the same, large, b-value but with different diffusion gradient waveforms. TDR is advantageous as it employs standard acquisition sequences, does not make any assumptions on the underlying tissue structure and does not require any model fitting, avoiding issues related to model degeneracy. This work for the first time introduces and optimises the TDR method in simulation for a range of different tissues and scanner constraints and validates it in a pre-clinical demonstration. We consider both substrates containing cylinders and spherical structures, representing cell soma in tissue. Our results show that contrasting an acquisition with short gradient duration, short diffusion time and high gradient strength with an acquisition with long gradient duration, long diffusion time and low gradient strength, maximises the TDR contrast for a wide range of pore configurations. Additionally, in the presence of Rician noise, computing TDR from a subset (50% or fewer) of the acquired diffusion gradients rather than the entire shell as proposed originally further improves the contrast. In the last part of the work the results are demonstrated experimentally on rat spinal cord. In line with simulations, the experimental data shows that optimised TDR improves the contrast compared to non-optimised TDR. Furthermore, we find a strong correlation between TDR and histology measurements of axon diameter. In conclusion, we find that TDR has great potential and is a very promising alternative (or potentially complement) to model-based approaches for informing on pore sizes and restricted diffusion in general.

Differential impacts of Cntnap2 heterozygosity and Cntnap2 null homozygosity on axon and myelinated fiber development in mouse.

Over the last decade, a large variety of alterations of the Contactin Associated Protein 2 (CNTNAP2) gene, encoding Caspr2, have been identified in several neuronal disorders, including neurodevelopmental disorders and peripheral neuropathies. Some of these alterations are homozygous but most are heterozygous, and one of the current challenges is to estimate to what extent they could affect the functions of Caspr2 and contribute to the development of these pathologies. Notably, it is not known whether the disruption of a single CNTNAP2 allele could be sufficient to perturb the functions of Caspr2. To get insights into this issue, we questioned whether Cntnap2 heterozygosity and Cntnap2 null homozygosity in mice could both impact, either similarly or differentially, some specific functions of Caspr2 during development and in adulthood. We focused on yet poorly explored functions of Caspr2 in axon development and myelination, and performed a morphological study from embryonic day E17.5 to adulthood of two major brain interhemispheric myelinated tracts, the anterior commissure (AC) and the corpus callosum (CC), comparing wild-type (WT), Cntnap2 -/- and Cntnap2 +/- mice. We also looked for myelinated fiber abnormalities in the sciatic nerves of mutant mice. Our work revealed that Caspr2 controls the morphology of the CC and AC throughout development, axon diameter at early developmental stages, cortical neuron intrinsic excitability at the onset of myelination, and axon diameter and myelin thickness at later developmental stages. Changes in axon diameter, myelin thickness and node of Ranvier morphology were also detected in the sciatic nerves of the mutant mice. Importantly, most of the parameters analyzed were affected in Cntnap2 +/- mice, either specifically, more severely, or oppositely as compared to Cntnap2 -/- mice. In addition, Cntnap2 +/- mice, but not Cntnap2 -/- mice, showed motor/coordination deficits in the grid-walking test. Thus, our observations show that both Cntnap2 heterozygosity and Cntnap2 null homozygosity impact axon and central and peripheral myelinated fiber development, but in a differential manner. This is a first step indicating that CNTNAP2 alterations could lead to a multiplicity of phenotypes in humans, and raising the need to evaluate the impact of Cntnap2 heterozygosity on the other neurodevelopmental functions of Caspr2.

Novel insights into axon diameter and myelin content in late childhood and adolescence.

White matter microstructural development in late childhood and adolescence is driven predominantly by increasing axon density and myelin thickness. Ex vivo studies suggest that the increase in axon diameter drives developmental increases in axon density observed with pubertal onset. In this cross-sectional study, 50 typically developing participants aged 8-18years were scanned using an ultra-strong gradient magnetic resonance imaging scanner. Microstructural properties, including apparent axon diameter $({d}_a)$, myelin content, and g-ratio, were estimated in regions of the corpus callosum. We observed age-related differences in ${d}_a$, myelin content, and g-ratio. In early puberty, males had larger ${d}_a$ in the splenium and lower myelin content in the genu and body of the corpus callosum, compared with females. Overall, this work provides novel insights into developmental, pubertal, and cognitive correlates of individual differences in apparent axon diameter and myelin content in the developing human brain.

Novel neuron-Schwann cell co-culture models to study peripheral nerve degeneration and regeneration.

Novel neuron-Schwann cell co-culture models to study peripheral nerve degeneration and regeneration.

Studying the Effect of Maternal Anemia and Neonatal Hematological Indices on Auditory Brainstem Responses of Newborn Babies

Purpose: Animal studies have shown the effect of maternal anemia (MA) and neonatal iron deficiency (ID) on the auditory system of young ones. However, the evidence supporting the same in human infants is inconclusive. Hence, the present study aims to investigate the effect of MA and neonatal iron status on the auditory brainstem responses (ABRs) of newborn babies. Materials and Methods: A total of 100 babies (gestational age ≥34 weeks) were divided into “Normal” group-57 babies without MA, “Mild” group-22 mild MA babies, and “Moderate” group-21 moderate MA babies. The ABR was recorded using 80 dBnHL click stimuli at 10 and 90 Hz repetition rates. Results: The results based on MA showed a significantly better presence of ABR peaks for the normal group than mild and moderate groups at a higher rate and no significant difference for latency and amplitude measures across the groups. The results based on neonatal hematological indices showed that the ABR measures were better in babies with probable ID which could be attributed to neural hyperactivity and an increase in axonal diameter leading to faster nerve conduction velocity. Conclusion: The auditory system maturation in newborn babies is influenced by maternal as well as neonatal iron status.

Pinostrobin from Boesenbergia rotunda attenuates oxidative stress and promotes functional recovery in rat model of sciatic nerve crush injury.

Oxidative stress plays a role in the delay of peripheral nerve regeneration after injury. The accumulation of free radicals results in nerve tissue damage and dorsal root ganglion (DRG) neuronal death. Pinostrobin (PB) is one of the bioflavonoids from Boesenbergia rotunda and has been reported to possess antioxidant capacity and numerous pharmacological activities. Therefore, this study aimed to investigate the effects of PB on peripheral nerve regeneration after injury. Male Wistar rats were randomly divided into 5 groups including control, sham, sciatic nerve crush injury (SNC), SNC + 20 mg/kg PB, and SNC + 40 mg/kg PB. Nerve functional recovery was observed every 7 days. At the end of the study, the sciatic nerve and the DRG were collected for histological and biochemical analyses. PB treatment at doses of 20 and 40 mg/kg reduced oxidative stress by up-regulating endogenous glutathione. The reduced oxidative stress in PB-treated rats resulted in increased axon diameters, greater number of DRG neurons, and p-ERK1/2 expression in addition to faster functional recovery within 4 weeks compared to untreated SNC rats. The results indicated that PB diminished the oxidative stress-induced nerve injury. These effects should be considered in the treatment of peripheral nerve injury.