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1.
Materials (Basel) ; 17(3)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38592008

ABSTRACT

Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a biobased and biodegradable polymer. This polymer is considered promising, but it is also rather expensive. The objective of this study was to compound PHBV with three different organic fillers considered waste: human hair waste (HHW), sawdust (SD) and chitin from shrimp shells. Thus, the cost of the biopolymer is reduced, and, at the same time, waste materials are valorised into something useful. The composites prepared were characterised by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), tensile strength and scanning electron micrograph (SEM). Tests showed that chitin and HHW did not have a reinforcing effect on tensile strength while the SD increased the tensile strength at break to a certain degree. The biodegradation of the different composites was evaluated by a soil burial test for five months. The gravimetric test showed that neat PHBV was moderately degraded (about 5% weight loss) while reinforcing the polymer with organic waste clearly improved the biodegradation. The strongest biodegradation was achieved when the biopolymer was compounded with HHW (35% weight loss). The strong biodegradation of HHW was further demonstrated by characterisation by Fourier-transform infrared spectroscopy (FTIR) and solid-state nuclear magnetic resonance (NMR). Characterisation by SEM showed that the surfaces of the biodegraded samples were eroded.

2.
Glob Chall ; 8(3): 2300098, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38486927

ABSTRACT

A fungal biorefinery is presented to valorize food waste to fungal monofilaments with tunable properties for different textile applications. Rhizopus delemar is successfully grown on bread waste and the fibrous cell wall is isolated. A spinnable hydrogel is produced from cell wall by protonation of amino groups of chitosan followed by homogenization and concentration. Fungal hydrogel is wet spun to form fungal monofilaments which underwent post-treatments to tune the properties. The highest tensile strength of untreated monofilaments is 65 MPa (and 4% elongation at break). The overall highest tensile strength of 140.9 MPa, is achieved by water post-treatment. Moreover, post-treatment with 3% glycerol resulted in the highest elongation % at break, i.e., 14%. The uniformity of the monofilaments also increased after the post-treatments. The obtained monofilaments are compared with commercial fibers using Ashby's plots and potential applications are discussed. The wet spun monofilaments are located in the category of natural fibers in Ashby's plots. After water and glycerol treatments, the properties shifted toward metals and elastomers, respectively. The compatibility of the monofilaments with human skin cells is supported by a biocompatibility assay. These findings demonstrate fungal monofilaments with tunable properties fitting a wide range of sustainable textiles applications.

3.
Ageing Res Rev ; 95: 102228, 2024 03.
Article in English | MEDLINE | ID: mdl-38354985

ABSTRACT

Although sex differences in amyotrophic lateral sclerosis (ALS) have not been studied systematically, numerous clinical and preclinical studies have shown sex to be influential in disease prognosis. Moreover, with the development of advanced imaging tools, the difference between male and female brain in structure and function and their response to neurodegeneration are more definitive. As discussed in this review, ALS patients exhibit a sex bias pertaining to the features of the disease, and their clinical, pathological, (and pathophysiological) phenotypes. Several epidemiological studies have indicated that this sex disparity stems from various aetiologies, including sex-specific brain structure and neural functioning, genetic predisposition, age, gonadal hormones, susceptibility to traumatic brain injury (TBI)/head trauma and lifestyle factors.


Subject(s)
Amyotrophic Lateral Sclerosis , Humans , Male , Female , Amyotrophic Lateral Sclerosis/epidemiology , Amyotrophic Lateral Sclerosis/genetics , Brain/pathology , Biology
4.
Front Neurosci ; 17: 1276495, 2023.
Article in English | MEDLINE | ID: mdl-37901420

ABSTRACT

Introduction: Severe traumatic brain injury (TBI) is the world's leading cause of permanent neurological disability in children. TBI-induced neurological deficits may be driven by neuroinflammation post-injury. Abnormal activity of SH2 domain-containing inositol 5' phosphatase-1 (SHIP-1) has been associated with dysregulated immunological responses, but the role of SHIP-1 in the brain remains unclear. The current study investigated the immunoregulatory role of SHIP-1 in a mouse model of moderate-severe pediatric TBI. Methods: SHIP-1+/- and SHIP-1-/- mice underwent experimental TBI or sham surgery at post-natal day 21. Brain gene expression was examined across a time course, and immunofluorescence staining was evaluated to determine cellular immune responses, alongside peripheral serum cytokine levels by immunoassays. Brain tissue volume loss was measured using volumetric analysis, and behavior changes both acutely and chronically post-injury. Results: Acutely, inflammatory gene expression was elevated in the injured cortex alongside increased IBA-1 expression and altered microglial morphology; but to a similar extent in SHIP-1-/- mice and littermate SHIP-1+/- control mice. Similarly, the infiltration and activation of CD68-positive macrophages, and reactivity of GFAP-positive astrocytes, was increased after TBI but comparable between genotypes. TBI increased anxiety-like behavior acutely, whereas SHIP-1 deficiency alone reduced general locomotor activity. Chronically, at 12-weeks post-TBI, SHIP-1-/- mice exhibited reduced body weight and increased circulating cytokines. Pro-inflammatory gene expression in the injured hippocampus was also elevated in SHIP-1-/- mice; however, GFAP immunoreactivity at the injury site in TBI mice was lower. TBI induced a comparable loss of cortical and hippocampal tissue in both genotypes, while SHIP-1-/- mice showed reduced general activity and impaired working memory, independent of TBI. Conclusion: Together, evidence does not support SHIP-1 as an essential regulator of brain microglial morphology, brain immune responses, or the extent of tissue damage after moderate-severe pediatric TBI in mice. However, our data suggest that reduced SHIP-1 activity induces a greater inflammatory response in the hippocampus chronically post-TBI, warranting further investigation.

5.
J Neurotrauma ; 40(3-4): 365-382, 2023 02.
Article in English | MEDLINE | ID: mdl-36070444

ABSTRACT

Pediatric traumatic brain injury (TBI) is a major public health issue, and a risk factor for the development of post-traumatic epilepsy that may profoundly impact the quality of life for survivors. As the majority of neurotrauma research is focused on injury to the adult brain, our understanding of the developing brain's response to TBI remains incomplete. Neuroinflammation is an influential pathophysiological mechanism in TBI, and is thought to increase neuronal hyperexcitability, rendering the brain more susceptible to the onset of seizures and/or epileptogenesis. We here hypothesized that peripheral blood-derived macrophages, recruited into the injured brain via C-C motif ligand 2 (CCL2) chemokine/C-C chemokine receptor type 2 (CCR2) signaling, contributes to neuroinflammation and thus seizure susceptibility after experimental pediatric TBI. Using Ccr2 gene-deficient mice in the controlled cortical impact (CCI) model of TBI, in 3-week-old male mice we found that TBI led to an increase in susceptibility to pentylenetetrazol (PTZ)-evoked seizures, associated with considerable cortical tissue loss, a robust cellular neuroinflammatory response, and oxidative stress. Intriguingly, although Ccr2-deficiency increased CCL2 levels in serum, it did not exacerbate seizure susceptibility or the neuroinflammatory cellular response after pediatric TBI. Similarly, acute post-injury treatment with a CCR2 antagonist did not influence seizure susceptibility or the extent of tissue damage in wild-type (WT) mice. Together, our findings suggest that CCR2 is not a crucial driver of epileptogenesis or neuroinflammation after TBI in the developing brain. We propose that age may be an important factor differentiating our findings from previous studies in which targeting CCL2/CCR2 has been reported to be anti-inflammatory, neuroprotective or anti-seizure.


Subject(s)
Brain Injuries, Traumatic , Neuroinflammatory Diseases , Mice , Male , Animals , Quality of Life , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/genetics , Inflammation , Brain/metabolism , Chemokine CCL2/genetics , Receptors, CCR2/genetics , Receptors, CCR2/metabolism , Mice, Inbred C57BL
6.
Neuroimage Clin ; 34: 103016, 2022.
Article in English | MEDLINE | ID: mdl-35483133

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is characterized by transactive response DNA-binding protein 43 (TDP-43) pathology, progressive loss of motor neurons and muscle dysfunction. Symptom onset can be insidious and diagnosis challenging. Conventional neuroimaging is used to exclude ALS mimics, however more advanced neuroimaging techniques may facilitate an earlier diagnosis. Here, we investigate the potential for neurite orientation dispersion and density imaging and diffusion tensor imaging (DTI) to detect microstructural changes in an experimental model of ALS with neuronal doxycycline (Dox)-suppressible overexpression of human TDP-43 (hTDP-43). In vivo diffusion-weighted imaging (DWI) was acquired 1- and 3- weeks following the initiation of hTDP-43 expression (post-Dox) to investigate whether neurite density imaging (NDI) and orientation dispersion imaging (ODI) are affected early in this preclinical model of ALS and if so, how these metrics compare to those derived from the diffusion tensor. Tract-based spatial statistics at 1-week post-Dox, i.e. very early in the disease stage, demonstrated increased NDI in TDP-43 mice but no change in ODI or DTI metrics. At 3-weeks post-Dox, a reduced pattern of increased NDI was observed along with widespread increases in ODI, and decreased fractional anisotropy (FA), apparent diffusion coefficient (ADC) and axial diffusivity (AD). A hypothesis driven analysis of the bilateral corticospinal tracts demonstrated that at 1-week post-Dox, ODI was significantly increased caudally but decreased in the motor cortex of TDP-43 mice. Decreased cortical ODI had normalized by 3-weeks post-Dox and only significant increases were observed. A similar, but inverse pattern in FA was also observed. Together, these results suggest a non-monotonic relationship between DWI metrics and pathophysiological progression with TDP-43 mice exhibiting significantly altered diffusion metrics consistent with early inflammation followed by progressive axonal degeneration. Importantly, significant group-wise changes were observed in the earliest stages of disease when subtle pathology may be more elusive to traditional structural imaging techniques.


Subject(s)
Amyotrophic Lateral Sclerosis , Diffusion Tensor Imaging , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/pathology , Animals , DNA-Binding Proteins , Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging/methods , Humans , Mice , Neurites/pathology
7.
Bioengineered ; 13(4): 10010-10025, 2022 04.
Article in English | MEDLINE | ID: mdl-35416127

ABSTRACT

Agricultural residues are constantly increasing with increased farming processes, and improper disposal is detrimental to the environment. Majority of these waste residues are rich in lignocellulose, which makes them suitable substrate for bacterial fermentation in the production of value-added products. In this study, bacterial cellulose (BC), a purer and better form of cellulose, was produced by two Komagataeibacter sp. isolated from rotten banana and kombucha drink using corncob (CC) and sugarcane bagasse (SCB) enzymatic hydrolyzate, under different fermentation conditions, that is, static, continuous, and intermittent agitation. The physicochemical and mechanical properties of the BC films were then investigated by Fourier Transformed Infrared Spectroscopy (FTIR), Thermogravimetry analysis, Field Emission Scanning Electron Microscopy (FE-SEM), and Dynamic mechanical analysis. Agitation gave a higher BC yield, with Komagataeibacter sp. CCUG73629 producing BC from CC with a dry weight of 1.6 g/L and 1.4 g/L under continuous and intermittent agitation, respectively, compared with that of 0.9 g/L in HS medium. While BC yield of dry weight up to 1.2 g/L was obtained from SCB by Komagataeibacter sp. CCUG73630 under continuous agitation compared to that of 0.3 g/L in HS medium. FTIR analysis showed BC bands associated with cellulose I, with high thermal stability. The FE-SEM analysis showed that BC fibers were highly ordered and densely packed. Although the BC produced by both strains showed similar physicochemical and morphological properties, the BC produced by the Komagataeibacter sp. CCUG73630 in CC under intermittent agitation had the best modulus of elasticity, 10.8 GPa and tensile strength, 70.9 MPa.


Subject(s)
Acetobacteraceae , Saccharum , Acetobacteraceae/chemistry , Acetobacteraceae/metabolism , Agriculture , Cellulose/metabolism , Culture Media/chemistry , Fermentation , Saccharum/metabolism
8.
Int J Biol Macromol ; 209(Pt A): 618-630, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35427640

ABSTRACT

Here, cell wall of a zygomycete fungus, Rhizopus delemar, grown on bread waste was wet spun into monofilaments. Using the whole cell wall material omits the common chitosan isolation and purification steps and leads to higher material utilization. The fungal cell wall contained 36.9% and 19.7% chitosan and chitin, respectively. Solid state NMR of the fungal cell wall material confirmed the presence of chitosan, chitin, and other carbohydrates. Hydrogels were prepared by ultrafine grinding of the cell wall, followed by addition of lactic acid to protonate the amino groups of chitosan, and subsequently wet spun into monofilaments. The monofilament inhibited the growth of Bacillus megaterium (Gram+ bacterium) and Escherichia coli (Gram- bacterium) significantly (92.2% and 99.7% respectively). Cytotoxicity was evaluated using an in vitro assay with human dermal fibroblasts, indicating no toxic inducement from exposure of the monofilaments. The antimicrobial and biocompatible fungal monofilaments, open new avenues for sustainable biomedical textiles from abundant food waste.


Subject(s)
Chitosan , Refuse Disposal , Anti-Bacterial Agents/pharmacology , Chitin/chemistry , Chitosan/chemistry , Escherichia coli , Food , Humans
9.
Transl Neurodegener ; 11(1): 17, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35287738

ABSTRACT

BACKGROUND: Multiple lines of evidence suggest possible impairment of the glymphatic system in amyotrophic lateral sclerosis (ALS). To investigate this, we used in vivo magnetic resonance imaging (MRI) to assess glymphatic function early in the course of disease in a transgenic mouse with doxycycline (Dox)-controlled expression of cytoplasmic human TDP-43 (hTDP-43ΔNLS), mimicking the key pathology implicated in ALS. METHODS: Adult TDP-43 transgenic and littermate monogenic control mice underwent longitudinal multimodal MRI one and three weeks after the cessation of Dox feed, together with weekly rotarod assessments of motor performance. Glymphatic function was assessed using dynamic contrast-enhanced MRI to track the clearance of an MR contrast agent injected into the cisterna magna. RESULTS: Compared to their littermate controls, TDP-43 mice exhibited progressive neurodegeneration including that within the primary motor cortex, primary somatosensory cortex and corticospinal tract, significant weight loss including gastrocnemius atrophy, and shortened telomere length. Furthermore, in the presence of this ALS-like phenotype, these mice have significantly disrupted glymphatic function. CONCLUSIONS: Although the relationship between glymphatic clearance and ALS disease progression remains to be elucidated, these changes occurred very early in the disease course. This provides initial evidence to suggest that the glymphatic system might be a potential therapeutic target in the treatment of ALS.


Subject(s)
Amyotrophic Lateral Sclerosis , Amyotrophic Lateral Sclerosis/diagnostic imaging , Amyotrophic Lateral Sclerosis/genetics , Amyotrophic Lateral Sclerosis/metabolism , Animals , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Disease Models, Animal , Disease Progression , Mice , Mice, Transgenic , Telomere/metabolism , Telomere/pathology , Telomere Shortening
10.
Polymers (Basel) ; 13(12)2021 Jun 21.
Article in English | MEDLINE | ID: mdl-34205755

ABSTRACT

The work demonstrates the utilization of fractionalized lignin from the black liquor of soda pulping for the development of starch-lignin biocomposites. The effect of ultrafine friction grinding on lignin particle size and properties of the biocomposites was investigated. Microscopic analysis and membrane filtration confirmed the reduction of lignin particle sizes down to micro and nanoparticles during the grinding process. Field Emission Scanning Electron Microscopy confirmed the compatibility between lignin particles and starch in the composites. The composite films were characterized for chemical structure, ultraviolet blocking, mechanical, and thermal properties. Additional grinding steps led to the reduction of large lignin particles and the produced particles were uniform. The formation of 7.7 to 11.3% lignin nanoparticles was confirmed in the two steps of membrane filtration. The highest tensile strain of the biocomposite films were 5.09 MPa, which displays a 40% improvement compared to starch films. Further, thermal stability of the composite films was better than that of starch films. The results from ultraviolet transmission showed that the composite films could act as an ultraviolet barrier in packaging applications.

11.
Polymers (Basel) ; 13(13)2021 Jun 28.
Article in English | MEDLINE | ID: mdl-34203312

ABSTRACT

Adipic acid was evaluated as a novel solvent for wet spinning of chitosan fibers. A solvent with two carboxyl groups could act as a physical crosslinker between the chitosan chains, resulting in improved properties of the fibers. The performance of adipic acid was compared with conventional solvents, i.e., lactic, citric, and acetic acids. Chitosan solutions were injected into a coagulation bath to form monofilaments. Sodium hydroxide (NaOH) and its mixture with ethanol (EtOH) were used as coagulation agents. Scanning electron microscopy confirmed the formation of uniform chitosan monofilaments with an even surface when using adipic acid as solvent. These monofilaments generally showed higher mechanical strength compared to that of monofilaments produced using conventional solvents. The highest Young's modulus, 4.45 GPa, was recorded for adipic acid monofilaments coagulated in NaOH-EtOH. This monofilament also had a high tensile strength of 147.9 MPa. Furthermore, taking advantage of chitosan insolubility in sulfuric acid (H2SO4) at room temperature, chitosan fibers were successfully formed upon coagulation in H2SO4-EtOH. The dewatering of fibers using EtOH before drying resulted in a larger fiber diameter and lower mechanical strength. Adipic acid fibers made without dehydration illustrated 18% (for NaOH), 46% (for NaOH-EtOH), and 91% (for H2SO4-EtOH) higher tensile strength compared to those made with dehydration.

13.
Cereb Cortex ; 31(10): 4411-4419, 2021 08 26.
Article in English | MEDLINE | ID: mdl-33860291

ABSTRACT

Sports-related concussion (SRC) is a serious health concern. However, the temporal profile of neuropathophysiological changes after SRC and how these relate to biological sex are still poorly understood. This preliminary study investigated whether diffusion-weighted magnetic resonance imaging (dMRI) was sensitive to neuropathophysiological changes following SRC; whether these changes were sex-specific; and whether they persisted beyond the resolution of self-reported symptoms. Recently concussed athletes (n = 14), and age- and education-matched nonconcussed control athletes (n = 16), underwent MRI 24-48-h postinjury and again at 2-week postinjury (i.e., when cleared to return-to-play). Male athletes reported more symptoms and greater symptom severity compared with females. dMRI revealed white matter differences between athletes with SRC and their nonconcussed counterparts at 48-h postinjury. These differences were still present at 2-week postinjury, despite SRC athletes being cleared to return to play and may indicate increased cerebral vulnerability beyond the resolution of subjective symptoms. Furthermore, we identified sex-specific differences, with male SRC athletes having significantly greater white matter disruption compared with female SRC athletes. These results have important implications for the management of concussion, including guiding return-to-play decisions, and further improve our understanding regarding the role of sex in SRC outcomes.


Subject(s)
Athletic Injuries/diagnostic imaging , Brain Concussion/diagnostic imaging , White Matter/diagnostic imaging , Adolescent , Adult , Diffusion Magnetic Resonance Imaging , Female , Humans , Image Processing, Computer-Assisted , Male , Self Report , Sex Characteristics , Soccer/injuries , Young Adult
14.
Chemosphere ; 278: 130443, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33836399

ABSTRACT

It has been suggested that cellulolytic enzymes can be effective on the degradation of PLA samples. The idea was investigated by examining the impact of cellulase on degradation of PLA and PLA-jute (64/36) composite in an aqueous medium. The obtained results demonstrated 55% and 61% thickness reduction in PLA and PLA-jute specimens after four months of treatment, respectively. Gel permeation chromatography (GPC) showed significant decline in the number average molecular weight (Mn) approximately equal to 85% and 80% for PLA and PLA-jute in comparison with their control. The poly dispersity index (PDI) of PLA and PLA-jute declined 41% and 49% that disclosed more homogenous distribution in molecular weight of the polymer after treatment with cellulase. The cellulase promiscuity effect on PLA degradation was further revealed by Fourier-transform infrared spectroscopy (FT-IR) analysis where substantial decrease in the peak intensities of the polymer related functional groups were observed. In addition, PLA biodegradation was studied in more detail by differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA) of control and cellulase treated specimens. The obtained results confirmed the promiscuous function of cellulase in the presence or the absence of jute as the specific substrate of cellulase. This can be considered as a major breakthrough to develop effective biodegradation processes for PLA products at the end of their life cycle.


Subject(s)
Cellulase , Polyesters , Polymers , Spectroscopy, Fourier Transform Infrared
15.
J Neuroinflammation ; 18(1): 72, 2021 Mar 17.
Article in English | MEDLINE | ID: mdl-33731173

ABSTRACT

BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability in young children, yet the factors contributing to poor outcomes in this population are not well understood. TBI patients are highly susceptible to nosocomial infections, which are mostly acquired within the first week of hospitalization, and such infections may modify TBI pathobiology and recovery. In this study, we hypothesized that a peripheral immune challenge such as lipopolysaccharide (LPS)-mimicking a hospital-acquired infection-would worsen outcomes after experimental pediatric TBI, by perpetuating the inflammatory immune response. METHODS: Three-week-old male mice received either a moderate controlled cortical impact or sham surgery, followed by a single LPS dose (1 mg/kg i.p.) or vehicle (0.9% saline) at 4 days post-surgery, then analysis at 5 or 8 days post-injury (i.e., 1 or 4 days post-LPS). RESULTS: LPS-treated mice exhibited a time-dependent reduction in general activity and social investigation, and increased anxiety, alongside substantial body weight loss, indicating transient sickness behaviors. Spleen-to-body weight ratios were also increased in LPS-treated mice, indicative of persistent activation of adaptive immunity at 4 days post-LPS. TBI + LPS mice showed an impaired trajectory of weight gain post-LPS, reflecting a synergistic effect of TBI and the LPS-induced immune challenge. Flow cytometry analysis demonstrated innate immune cell activation in blood, brain, and spleen post-LPS; however, this was not potentiated by TBI. Cytokine protein levels in serum, and gene expression levels in the brain, were altered in response to LPS but not TBI across the time course. Immunofluorescence analysis of brain sections revealed increased glia reactivity due to injury, but no additive effect of LPS was observed. CONCLUSIONS: Together, we found that a transient, infection-like systemic challenge had widespread effects on the brain and immune system, but these were not synergistic with prior TBI in pediatric mice. These findings provide novel insight into the potential influence of a secondary immune challenge to the injured pediatric brain, with future studies needed to elucidate the chronic effects of this two-hit insult.


Subject(s)
Brain Injuries, Traumatic/immunology , Brain Injuries, Traumatic/pathology , Cross Infection/immunology , Encephalitis/immunology , Encephalitis/pathology , Adaptive Immunity/immunology , Animals , Anxiety/etiology , Anxiety/psychology , Behavior, Animal , Brain Injuries, Traumatic/psychology , Cerebral Cortex/pathology , Disease Models, Animal , Encephalitis/psychology , Lipopolysaccharides/pharmacology , Male , Mice , Mice, Inbred C57BL , Motor Activity , Social Behavior , Weight Loss
16.
Exp Neurol ; 339: 113652, 2021 05.
Article in English | MEDLINE | ID: mdl-33609501

ABSTRACT

Young children have a high risk of sustaining a traumatic brain injury (TBI), which can have debilitating life-long consequences. Importantly, the young brain shows particular vulnerability to injury, likely attributed to ongoing maturation of the myelinating nervous system at the time of insult. Here, we examined the effect of acute treatment with the partial tropomyosin receptor kinase B (TrkB) agonist, LM22A-4, on pathological and neurobehavioral outcomes after pediatric TBI, with the hypothesis that targeting TrkB would minimize tissue damage and support functional recovery. We focused on myelinated tracts-the corpus callosum and external capsules-based on recent evidence that TrkB activation potentiates oligodendrocyte remyelination. Male mice at postnatal day 21 received an experimental TBI or sham surgery. Acutely post-injury, extensive cell death, a robust glial response and disruption of compact myelin were evident in the injured brain. TBI or sham mice then received intranasal saline vehicle or LM22A-4 for 14 days. Behavior testing was performed from 4 weeks post-injury, and brains were collected at 5 weeks for histology. TBI mice showed hyperactivity, reduced anxiety-like behavior, and social memory impairments. LM22A-4 ameliorated the abnormal anxiolytic phenotype but had no effect on social memory deficits. Use of spectral confocal reflectance microscopy detected persistent myelin fragmentation in the external capsule of TBI mice at 5 weeks post-injury, which was accompanied by regionally distinct deficits in oligodendrocyte progenitor cells and post-mitotic oligodendrocytes, as well as chronic reactive gliosis and atrophy of the corpus callosum and injured external capsule. LM22A-4 treatment ameliorated myelin deficits in the perilesional external capsule, as well as tissue volume loss and the extent of reactive gliosis. However, there was no effect of this TrkB agonist on oligodendroglial populations detected at 5 weeks post-injury. Collectively, our results demonstrate that targeting TrkB immediately after TBI during early life confers neuroprotection and preserves myelin integrity, and this was associated with some improved neurobehavioral outcomes as the pediatric injured brain matures.


Subject(s)
Benzamides/administration & dosage , Brain Injuries, Traumatic/prevention & control , Membrane Glycoproteins/agonists , Myelin Sheath/drug effects , Neuroprotection/drug effects , Remyelination/drug effects , Animals , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/pathology , Disease Models, Animal , Drug Administration Schedule , Male , Mice , Mice, Inbred C57BL , Myelin Sheath/metabolism , Myelin Sheath/pathology , Neuroprotection/physiology , Protein-Tyrosine Kinases , Remyelination/physiology , Treatment Outcome
17.
Brain Imaging Behav ; 15(6): 2766-2774, 2021 Dec.
Article in English | MEDLINE | ID: mdl-33411159

ABSTRACT

Pediatric traumatic brain injury (pTBI) is a major community health concern. Due to ongoing maturation, injury to the brain at a young age can have devastating consequences in later life. However, how pTBI affects brain development, including white matter maturation, is still poorly understood. Here, we used advanced diffusion weighted imaging (DWI) to assess chronic white matter changes after experimental pTBI. Mice at post-natal day 21 sustained a TBI using the controlled cortical impact model and magnetic resonance imaging (MRI) was performed at 6 months post-injury using a 4.7 T Bruker scanner. Four diffusion shells with 81 directions and b-values of 1000, 3000, 5000, and 7000s/mm2 were acquired and analyzed using MRtrix3 software. Advanced DWI metrics, including fiber density, fiber cross-section and a combined fiber density and cross-section measure, were investigated together with three track-weighted images (TWI): the average pathlength map, mean curvature and the track density image. These advanced metrics were compared to traditional diffusion tensor imaging (DTI) metrics which indicated that TBI injured mice had reduced fractional anisotropy and increased radial diffusivity in the white matter when compared to age-matched sham controls. Consistent with previous findings, fiber density and TWI metrics appeared to be more sensitive to white matter changes than DTI metrics, revealing widespread reductions in fiber density and TWI metrics in pTBI mice compared to sham controls. These results provide additional support for the use of advanced DWI metrics in assessing white matter degeneration following injury and highlight the chronic outcomes that can follow pTBI.


Subject(s)
Brain Injuries, Traumatic , White Matter , Animals , Brain/diagnostic imaging , Brain Injuries, Traumatic/diagnostic imaging , Child , Diffusion Magnetic Resonance Imaging , Diffusion Tensor Imaging , Humans , Magnetic Resonance Imaging , Mice , White Matter/diagnostic imaging
18.
Int J Biol Macromol ; 167: 1126-1134, 2021 Jan 15.
Article in English | MEDLINE | ID: mdl-33188816

ABSTRACT

Chitin nanofibers (ChNFs) were extracted from Mucor indicus by a purification method followed by a mechanical treatment, cultivated under obtained optimum culture medium conditions to improve fungal chitin production rate. A semi synthetic media containing 50 g/l glucose was used for cultivation of the fungus in shake flasks. The cell wall analysis showed that N-acetyl glucosamine (GlcNAc) content, which is an indication of chitin content, was maximum in presence of 2.5 g/l H3PO4, 2.5 g/l of NaOH, 1 g/l of yeast extract, 1 mg/l of plant hormones, and 1 ml/l of trace metals. The chemical characterizations demonstrated that the isolated fibers had a degree of deacetylation lower than of 10%, and were phosphate free. The FTIR results revealed successful removal of different materials during the purification step. The FE-SEM of fibrillated chitin illustrated an average diameter of 28 nm. Finally, X-ray diffraction results showed that the crystallinity index of nanofibers was 82%.


Subject(s)
Chitin/chemistry , Culture Media/chemistry , Fungal Polysaccharides/chemistry , Mucor/chemistry , Nanofibers/chemistry , Biomass , Chemical Fractionation/methods , Chitin/isolation & purification , Chitosan/chemistry , Culture Media/analysis , Culture Media, Conditioned/analysis , Culture Media, Conditioned/chemistry , Phosphates/chemistry , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction
19.
Polymers (Basel) ; 12(12)2020 Nov 29.
Article in English | MEDLINE | ID: mdl-33260411

ABSTRACT

The present work is focused on the synthesis of bio-based thermoset polymers and their thermo-oxidative ageing and biodegradability. Toward this aim, bio-based thermoset resins with different chemical architectures were synthesized from lactic acid by direct condensation with ethylene glycol, glycerol and pentaerythritol. The resulting branched molecules with chain lengths (n) of three were then end-functionalized with methacrylic anhydride. The chemical structures of the synthesized lactic acid derivatives were confirmed by proton nuclear magnetic resonance spectroscopy (1H-NMR) and Fourier transform infrared spectroscopy (FT-IR) before curing. To evaluate the effects of structure on their properties, the samples were investigated by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and the tensile testing. The samples went through thermo-oxidative ageing and biodegradation; and their effects were investigated. FT-IR and 1H-NMR results showed that three different bio-based resins were synthesized using polycondensation and end-functionalization. Lactic acid derivatives showed great potential to be used as matrixes in polymer composites. The glass transition temperature of the cured resins ranged between 44 and 52 °C. Pentaerythritol/lactic acid cured resin had the highest tensile modulus and it was the most thermally stable among all three resins. Degradative processes during ageing of the samples lead to the changes in chemical structures and the variations in Young's modulus. Microscopic images showed the macro-scale surface degradation on a soil burial test.

20.
Sci Rep ; 10(1): 18170, 2020 10 23.
Article in English | MEDLINE | ID: mdl-33097782

ABSTRACT

Stroke is caused by obstructed blood flow (ischaemia) or unrestricted bleeding in the brain (haemorrhage). Global brain ischaemia occurs after restricted cerebral blood flow e.g. during cardiac arrest. Following ischaemic injury, restoration of blood flow causes ischaemia-reperfusion (I/R) injury which worsens outcome. Secondary injury mechanisms after any stroke are similar, and encompass inflammation, endothelial dysfunction, blood-brain barrier (BBB) damage and apoptosis. We developed a new model of transient global forebrain I/R injury (dual carotid artery ligation; DCAL) and compared the manifestations of this injury with those in a conventional I/R injury model (middle-cerebral artery occlusion; MCAo) and with intracerebral haemorrhage (ICH; collagenase model). MRI revealed that DCAL produced smaller bilateral lesions predominantly localised to the striatum, whereas MCAo produced larger focal corticostriatal lesions. After global forebrain ischaemia mice had worse overall neurological scores, although quantitative locomotor assessment showed MCAo and ICH had significantly worsened mobility. BBB breakdown was highest in the DCAL model while apoptotic activity was highest after ICH. VCAM-1 upregulation was specific to ischaemic models only. Differential transcriptional upregulation of pro-inflammatory chemokines and cytokines and TLRs was seen in the three models. Our findings offer a unique insight into the similarities and differences in how biological processes are regulated after different types of stroke. They also establish a platform for analysis of therapies such as endothelial protective and anti-inflammatory agents that can be applied to all types of stroke.


Subject(s)
Cerebrovascular Circulation/physiology , Hemorrhagic Stroke/pathology , Ischemic Stroke/pathology , Prosencephalon/blood supply , Reperfusion Injury/pathology , Animals , Anti-Inflammatory Agents/therapeutic use , Apoptosis/immunology , Blood-Brain Barrier/diagnostic imaging , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/pathology , Carotid Arteries/physiopathology , Cerebrovascular Circulation/drug effects , Collagenases/administration & dosage , Collagenases/adverse effects , Cytokines/genetics , Cytokines/immunology , Disease Models, Animal , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Hemorrhagic Stroke/drug therapy , Hemorrhagic Stroke/immunology , Hemorrhagic Stroke/physiopathology , Humans , Ischemic Stroke/drug therapy , Ischemic Stroke/immunology , Ischemic Stroke/physiopathology , Ligation , Locomotion/physiology , Magnetic Resonance Imaging , Male , Mice , Middle Cerebral Artery/physiopathology , Prosencephalon/diagnostic imaging , Prosencephalon/drug effects , Prosencephalon/pathology , Protective Agents/therapeutic use , Reperfusion Injury/drug therapy , Reperfusion Injury/immunology , Reperfusion Injury/physiopathology , Toll-Like Receptors/genetics , Transcriptional Activation/immunology
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