Folia neuropathologica最新文献

Parkinson's disease occurs due to loss of dopaminergic neurons, which alters the behavioural changes. The present study evaluates the effect of exercise on neurodegeneration against Parkinson's disease (PD) rat model and postulates its effect on novel molecular pathway. Rotenone was administered at 1 mg/kg s.c. every 48 h for 18 days for the in-duction of PD and exercise was given to rats for a period of 2 weeks after the confirmation of PD. Moreover, PD rats also received CGS 21680 (adenosine A2A receptor agonist, 0.5 mg/kg, i.p.) with exercise for a period of 2 weeks after confirmation of PD. The effect of exercise was assessed for motor and cognitive function in PD rats. The level of inflammatory cytokines and neurotransmitters was estimated in brain tissue of PD rats. Data of investigation reveal that exercise attenuates cognitive and motor function in PD rats, the exercise + CGS 21680 group shows reverse in the behavioural changes compared to exercise-treated PD rats. The level of inflammatory cytokines and neurochemical level ameliorated in the exercise-treated group compared to the PD group of rats, which is reversed in the exercise + CGS 21680 group. In conclusion, exercise protects neurodegeneration in PD rats by reducing aggregation of a-synuclein and activity of adenosine 2A receptor.

Parkinson's disease (PD) is characterized by microglia activation that leads to neuroinflammation. Heat shock transcription factor 1 (HSF1) is known to exert neuroprotective effects on neurodegenerative diseases. This study sought to analyse the role and mechanism of HSF1 in PD-induced neuroinflammation. The PD mouse models were established using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Animal behaviour capacities and neuronal damage were assessed via behavioural tests, tyrosine hydroxylase (TH) staining, and immunofluorescence. Levels of HSF1, miR-214-3p, nuclear factor of activated T cells 2 (NFATc2), and neuroinflammatory factors were detected via RT-qPCR, Western blotting, and ELISA.Binding relationships between HSF1 and miR-214-3p, miR-214-3p, and NFATc2 were tested via dual-luciferase or chromatin immunoprecipitation assays. Functional rescue experiments were designed to confirm the roles of miR-214-3p and NFATc2. HSF1 expression in brain tissues was downregulated upon MPTP treatment. HSF1 overexpression reduced motor deficits and loss of dopaminergic neurons, increased TH-positive neurons, and repressed neuroinflammation and micro-glia activation. Mechanically, HSF1 bound to the miR-214-3p promoter to increase its expression and inhibited NFATc2 transcription. miR-214-3p downregulation or NFATc2 overexpression reversed the inhibition of HSF1 overexpression on neuroinflammation and microglia activation. Overall, our findings unveiled the therapeutic role of HSF1 in PD-induced neuroinflammation and microglia activation via regulating miR-214-3p and NFATc2.

Astragaloside IV (AST IV), a major saponin component and active ingredient isolated from Astragalus membranaceus, has been well known to exhibit neuroprotective effects on diverse models of neurological diseases. Accumulating evidence suggests that dynamic balance of microglia/macrophages and astrocytes plays a vital role in neuroprotection and remyelination. However, dysregulation of microglia/macrophages and astrocytes orchestrate the pathogenesis of nervous system disorders. Therefore, we hypothesized that switching the transformation of microglia/macrophages and astrocytes into the neuroprotective M2 and A2 phenotypes, respectively, could be a potential target for therapeutic intervention. In the present study, we evaluate the efficacy of AST IV intervention on the effects of microglia/macrophages and astrocytes in an experimental autoimmune encephalomyelitis (EAE) model. AST IV improved paralysis and pathology of EAE by inhibiting the neurotoxic M1 microglia/macrophage phenotype, promoting M2 phenotype, shifting astrocytes towards a neuroprotective A2 phenotype, and protecting neurons from apoptosis through inhibition of TLR4/Myd88/NF-kB signalling pathway. Our study showed that AST IV could be a potential and promising drug for multiple sclerosis treatment.

Spontaneous intracranial hypotension (SIH) is a condition of negative intracranial pressure resulting from cerebrospinal fluid (CSF) leakage from the dural sac and is a well-known cause of orthostatic headache. Diagnosis and management can be difficult, often requiring coordination between multiple disciplines. Low CSF pressure and diffuse meningeal enhancement on brain MRI are the major instrumental features of the classic syndrome. Neuroimaging plays a key role in diagnosing SIH, particularly in atypical clinical presentations, by recognizing the specific findings of brain sagging on MRI and detecting the level of CSF leak on spinal imaging, thus guiding therapy accordingly. Since SIH could present with such a heterogeneous clinical picture, careful history taking and increased awareness of atypical presentations are of utmost importance. We review the existing SIH literature, illustrate management, clinical and neuroimaging findings of four consecutive patients with atypical SIH, who were recently referred to our hospital for evaluation to simplify and streamline the management of SIH.

Alzheimer's disease (AD) is a chronic, neurodegenerative disorder that affects the central nervous system and is found predominantly in elderly populations. As amyloid b protein (Ab) is one of the key players responsible for the pathogenesis of AD, we sought to investigate the protective effects of fisetin in an Ab1-42-induced rat model of AD. In this model, the protective effects of fisetin on learning and memory impairment induced by Ab1-42 were determined via the Morris water maze and passive avoidance test. Furthermore, the antioxidant activity, anti-inflammation, and apoptosis effect of fisetin were investigated using biochemical and immunohistochemical methods. The results showed that intragastric (i.g.) administration of fisetin (100, 50, and 25 mg/kg) improved previous learning and memory impairments in Ab1-42-treated rats. Hippocampal tissue from these fisetin-treated rats revealed that the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were markedly enhanced, and that the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were significantly reduced. Meanwhile, fisetin also significantly attenuated Ab1-42-induced cholinergic dysfunction such as elevated the activity of choline acetyltransferase (ChAT) and reduced the activity of acetylcholine esterase (AChE). In addition, hippocampal tissue obtained from fisetin-treated rats revealed a reversal of Ab1-42-induced effects on apoptotic pathway protein (caspase-3) expression and inflammatory response of glial fibrillary acidic protein (GFAP). This indicated that the amount of degenerating hippocampal neurons with apoptotic features was dramatically reduced after treatment with fisetin. Collectively, these findings suggest that fisetin has potential as a treatment agent for Alzheimer's disease and that its effects occur through several mechanisms, including inhibition of oxidative stress, adjustments to previous cholinergic dysfunction, anti-inflammatory actions, and decreased apoptotic activity.

Introduction: The aim of the study was to research the mechanism by which IGF2BP3 regulates glioma progression as well as its upstream regulatory axis.

Material and methods: The researched mRNA was determined using differential expression analysis based on bioinformatics data, and its upstream miRNAs and lncRNAs were predicted. Interaction between genes we researched was identified by dual-luciferase method. The viability, migration, invasion and angiogenesis of glioma were measured with MTT, colony formation, Transwell and Matrigel tube formation experiments, respectively. The mRNA expression of each gene was tested with qRT-PCR. IGF2BP3 level was determined via western blot and immunohistochemistry. Subcellular fractionation of FOXD3-AS1 was tested with fluorescence in situ hybridization. In vivo tumorigenesis assay was conducted on nude mice.

Results: IGF2BP3 high level in glioma cells correlated with patient's prognosis. Downregulation of IGF2BP3 restrained proliferation, migration, invasion and angiogenesis in glioma cells both in vitro and in vivo. There was a binding relationship between IGF2BP3 and miR-128-3p. Besides, FOXD3-AS1 as a sponge of miR-128-3p was located mainly in cytoplasm. Additionally, FOXD3-AS1 facilitated IGF2BP3 level via sponging miR-128-3p to stimulate glioma angiogenesis.

Conclusions: FOXD3-AS1 was a sponge of miR-128-3p through upregulating IGF2BP3 in glioma. Our findings shed light on diagnosis and treatment of glioma.

Introduction: The aim of the study was to explore the analgesic mechanism of effects of intrathecally administered interferon a (IFN-a) on chronic constriction injury (CCI) model rats.

Material and methods: 24 rats were divided into 6 groups, with 4 rats in each group, including the negative control group (Group N, no operation or treatment), the sham operation group (Group S, only the left sciatic nerve of the rats was exposed without ligation, 0.9% NaCl was intrathecally administered), and four experimental groups (CCI model was established first and then different drugs were intrathecally administered respectively), including 0.9% NaCl (Group C), IFN-a (Group CI), morphine (Group CM), and IFN-a combined with morphine (Group CIM). The mRNA levels of G proteins in both the spinal cord and dorsal root ganglia (DRG), as well as the content of amino acid and chemokine (C-X-C motif) ligand 6 (CXCL-6) in the cerebrospinal fluid were measured and analysed in each group.

Results: Intrathecal administration of IFN-a increased the mechanical pain threshold in CCI rats (33.32 ±1.36 vs. 21.08 ±1.59, p < 0.001), achieving the effect comparable to that of morphine (33.32 ±1.36 vs. 32.44 ±3.18, p > 0.05), increased the mRNA expression level of Gi protein (0.62 ±0.04 vs. 0.49 ±0.05, p = 0.006), and decreased the mRNA expression level of Gs protein in the spinal cord (1.80 ±0.16 vs. 2.06 ±0.15, p = 0.035) and DRG (2.11 ±0.10 vs. 2.79 ±0.13, p < 0.001). The intrathecal administration of both IFN-a and morphine can reduce the glutamate content in the cerebrospinal fluid (261.55 ±38.12 vs. 347.70 ±40.69, p = 0.012), but without any statistically significant difference in the content of CXCL-6 across all groups ( p > 0.05).

Conclusions: Intrathecal injection of IFN-a improved the mechanical pain threshold in CCI rats, so we inferred that intrathecal administration of IFN-a had analgesic effects on neuropathic pain, possibly related to the activation of G-proteincoupled µ receptors in the spinal cord and the inhibition of glutamate release.

As of now, there are no satisfactory treatments for spinal cord injury (SCI), so new therapeutic approaches are necessary to be explored. Adipose-derived mesenchymal stem cell exosomes (ADMSC-Exo), delightfully, show remarkable therapeutic effects. Therefore, we try to investigate the effects and mechanisms of ADMSC-Exo on SCI, as well as to provide novel approaches for the treatment of SCI. Adipose-derived mesenchymal stem cells (ADMSC) were isolated from rats and then exosomes (Exo) were extracted from the cells. The extracted Exo were identified by flow cytometry, transmission electron microscopy and nanoparticle tracking analysis (NTA). Then, the SCI rat model was established by the spinal cord impactor and injected with 200 µl PBS or Exo into their tail veins at 30 min, 24 h, and 48 h after surgery. The rats in the Control group and Exo group only exposed the spine. Motor function recovery was assessed on days 0, 7, 14, 21, and 28; histopathological changes and apoptosis levels in spinal cord tissues were observed by HE staining and TUNEL staining; the levels of inflammatory cytokines TNF-a, IL-6, and MCP-1 in spinal cord tissues were measured by ELISA; the expression levels of iNOS, IL-12, Arg1, and Mrc1 in spinal cord tissues were detected by qRT-PCR; and Nrf2, HO-1, and NQO1 protein expression in spinal cord tissues were detected by Western blot. ADMSC-Exo were successfully isolated and identified. ADMSC-Exo significantly relieved SCI and promoted motor function recovery in SCI rats. Moreover, ADMSC-Exo inhibited the expression of both inflammatory factors in the spinal cord tissues and M1 microglia, promoted the expression of M2 microglia, and activated the Nrf2/HO-1 pathway. Altogether, ADMSC-Exo can not only ameliorate SCI, but also promote the motor function recovery of rats. And the mechanism of ADMSC-Exo improving SCI may be achieved by activating Nrf2/HO-1 pathway and microglial polarization.

Brain tumours are heterogeneous and are classified comprehensively into molecular subtypes based on genetic alterations. Glioblastoma rapid progression, drug resistance, and recurrence have been scientifically linked to several factors, including its rapid growth rate, loss of apoptosis, pro-survival signalling, molecular heterogeneities and hallmark features to infiltrate vital brain structures. Because of the growing demand for design and development of delivery systems to overcome the existing limitations with the current therapeutic strategies, researchers are exploiting multifaceted aspects of nanotechnology to improve delivery of the drug payload. Firstly, nanotechnology procedures can improve the drug delivery methods with the help of nanoparticles (NPs) based nanovectors that can efficiently cross blood-brain barrier. Secondly, NPs also improve the cellular uptake of the drug as they can efficiently bind with the cell surface. Thirdly, NPs make the delivery of siRNAs and peptides possible, which can suppress the resistance of glioblastoma against TMZ or other chemo-preventive drugs. Fourthly, the use of metal NPs increases the efficiency of scanning or magnetic resonance imaging (MRI) procedures as they can produce contrasts in it. Lastly, NPs make it possible to use highly targeted co-administered strategies like chemoprevention and near infrared (NIR) or radiotherapy (RT). Hence, nanotechnology offers several promising solutions against glioblastoma by countering it on many fronts.