Folia neuropathologica最新文献

Introduction: Ischemic stroke (IS) is a disease caused by blood circulation disorders in the brain, ischemia, and hypoxia, resulting in ischemic necrosis or softening of localized brain tissue. Lipoic acid (ALA) is effective in resisting oxidative stress and alleviating the inflammatory response. This study evaluated the mechanism and effects of ALA on neurovascular unit remodeling after cerebral infarction.

Material and methods: In male C57BL/6 mice, cerebral infarction was induced using distal middle cerebral artery occlusion (dMCAO). In an in vitro model, cells were allocated to control, model, low dose, medium dose, and high dose groups. Infarct volume analysis, Evans blue extravasation, and enzyme-linked immunosorbent assay (ELISA) kits were used to evaluate the effects of ALA on IS. Cell Counting Kit-8 (CCK-8), 5-ethynyl 2'-deoxyuridine staining (EDU) staining, Western blot and immunohistochemistry were used to evaluate the mechanism of ALA in IS.

Results: This study found that the cerebral infarct volume of the ALA treatment group was similar to dMCAO mice. Treatment with ALA reduced the area of Evans blue compared with dMCAO mice at 7 days, and promoted astrocyte and pericyte proliferation in the peri-infarct area at 28 days. Meanwhile, treatment with ALA also increased vascular endothelial growth factor (VEGF), angiopoietin (Ang)-1 and claudin-5 protein expression levels, suppressed Ang-2 and matrix metalloproteinase-9 (MMP-9) protein expression levels, reduced neuronal apoptosis inhibitory protein (NAIP), leucine-rich repeat (LRR), and PYD domain-containing protein 3 (NLRP3) expression levels, and induced phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK) protein expression levels in cerebral infarction mice (all p < 0.05). On the other hand, ALA restored cell growth and the number of EDU cells, promoted cell migration, elevated superoxide dismutase (SOD) activity, reduced reactive oxygen species (ROS) and malondialdehyde (MDA) levels, and inhibited inflammation levels in the in vitro model (all p < 0.05). Treatment with ALA also suppressed NLRP3 and Ang-2 protein expression, reduced MMP-9 protein expression, and induced VEGF, Ang-1, claudin-5, and p-AMPK protein expression levels in the in vitro model (all p < 0.05).

Conclusions: ALA improved neurovascular unit remodeling after cerebral infarction through anti-inflammation effects via the AMPK/NLRP3 signaling pathway.

Introduction: Triggering receptor expressed on myeloid cells 2 (TREM2), part of the immunoglobulin superfamily, is implicated in various malignancies. However, its role in glioma formation remains unclear. Our study uncovered a potential mechanism involving TREM2.

Material and methods: The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets were utilized to assess the expression levels of TREM2 and DNAX-activating protein of 12 kDa (DAP12), explore their relationship, and evaluate their impact on patient prognosis. Western blotting was used to measure TREM2 expression in different glioma grades. Co-immunoprecipitation (Co-IP) was used to examine TREM2 and DAP12 interaction. Cell proliferation, invasion, and apoptosis were assessed via the cell proliferation test, cell invasion assay, and flow cytometry. An intracranial xenograft model was created by injecting tumor cells into nude mice. Mice injected with si-DAP12-transfected or non-transfected glioma cells were treated with 740Y-P, followed by survival analysis and immunohistochemistry.

Results: TREM2 and DAP12 were overexpressed in gliomas, with high levels associated with lower overall survival (p < 0.05 and p < 0.01). There was a strong positive correlation between TREM2 and DAP12 expression (p < 0.0001). TREM2 positively regulated DAP12, forming a complex that influenced glioma cell proliferation, apoptosis, and invasion (p < 0.05, p < 0.01, and p < 0.001). DAP12 knockdown significantly inhibited proliferation and invasion while promoting apoptosis of glioma cells, linked to the PI3K/AKT signaling pathway (p < 0.05 and p < 0.01). 740Y-P treatment counteracted the effects of DAP12 knockdown (p < 0.05, p < 0.01, p < 0.001, and p < 0.0001). In vivo, DAP12 knockdown inhibited glioma tumorigenicity (p < 0.001).

Conclusions: TREM2 positively regulates DAP12 and forms a complex that impacts glioma development via the PI3K/AKT pathway. Targeting the TREM2/DAP12 complex presents a potential therapeutic approach for gliomas.

Introduction: There remains uncertainty about the mechanism and specific location of the relative cortex with nonketotic hyperglycaemic hemichorea-hemiballismus (HC-HB). This paper aims to analyse the relationship between the disappearance of HC-HB and the supplementary motor area (SMA) infarction in a patient who recovered following an acute ischemic stroke.

Case presentation: An 83-year-old female patient with diabetes mellitus presenting with severe and refractory involuntary movement after hypoglycaemic therapy was referred to an outpatient neurosurgery department for further intervention. Laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) neuroimaging and physical examinations were performed. After a diagnosis of HC-HB was confirmed, the patient received hypoglycaemic therapy and haloperidol; however, there was no significant improvement. Brain MRI T1-weighted images and CT scans showed high signal intensity involving the bilateral putamen nucleus. CT perfusion and CT angiography showed a hypo-perfusion in the SMA of the right hemisphere without significant vascular occlusion. Then, aspirin and clopidogrel were administered, and the patient's left leg presented slight involuntary movement three days later. Interestingly, her involuntary movement disappeared again on the second day after the discontinuation of antiplatelet therapy. She was discharged three days later, and her symptoms did not recur during a follow-up for three months.

Conclusions: The SMA dysfunction caused by the acute infarction could terminate or reset the pathological neural path-way of nonketotic hyperglycaemic HC-HB and contribute to the disappearance of the involuntary movement on the contralateral side. The SMA may be a selective intervention target for patients with refractory nonketotic hyperglycaemic HC-HB.

Introduction: The aim was to explore the factors influencing hemorrhagic transformation (HT) after mechanical thrombectomy (MT) in acute anterior circulation large vessel occlusion stroke (ALVOS) and establish a corresponding prediction model.

Material and methods: A retrospective study was conducted on 180 ALVOS patients who underwent MT in our hospital between May 2022 and December 2023. The patients were divided into a bleeding group (134 cases) and a non-bleeding group (46 cases) based on whether there was intracranial hemorrhage in the immediate follow-up head CT after surgery. Logistic regression analysis was performed to explore the factors influencing HT after MT in ALVOS patients. A logistic regression prediction model based on risk factors was constructed. The predictive ability of the model was validated using receiver operating characteristic (ROC) curves.

Results: Significant differences were detected between the bleeding group and the non-bleeding group in terms of age, diabetes, NIHSS score on admission, time from onset to admission, time from onset to vascular recanalization, number of embolectomy attempts, and application of tirofiban (p < 0.05). Diabetes, NIHSS score on admission, time from onset to admission, time from onset to vascular recanalization, number of embolectomy attempts, and application of tirofiban were all significant factors influencing HT in ALVOS patients who underwent MT (p < 0.05). The logistic risk prediction model was constructed using the following model: Logit (P) = 0.625 × combined diabetes + 0.071 × NIHSS score + 0.035 × onset to hospital time + 2.321 × onset to vascular recanalization time + 1.461 × number of embolectomy attempts + 0.993 × application of tirofiban. The model had the likelihood ratio chi square (c2) = 196.85, DF = 6, p 2.03, the AUC was 0.882, 95% CI was 0.792-0.175, Z = 20.331, p < 0.001, with the predictive sensitivity of 85.35% and the specificity of 85.74%.

Conclusions: Age, diabetes, NIHSS score on admission, time from onset to admission, time from onset to vascular recanalization, number of thrombectomy attempts, and use of tirofiban were independent risk factors for HT after MT in ALVOS patients. A logistic risk prediction model incorporating independent risk factors had some predictive value for HT after thrombolysis.

Vitamin B 12 deficiency can cause subacute combined degeneration of the spinal cord and cerebellar lesions. The patient, a 78-year-old woman, presented with an unstable gait, speech impairment and memory decline for one month. The neurological examination revealed ataxia, cerebellar speech disorder and mild cognitive impairment. Head and cervical vertebra magnetic resonance imaging (MRI) showed spinal cord and cerebellar lesions. The patient's symptoms improved after supplementation with vitamin B 12 . We found few reports of such cases in the literature. In this case report, we describe the entire diagnostic and treatment process of vitamin B 12 deficiency involving cerebellar lesions and briefly discuss the related pathogenesis, research progress and treatment.

Introduction: Neuroinflammation plays a significant role in the pathological progression of traumatic brain injury (TBI) and represents a promising therapeutic target. The present study focused on exploring the mechanism of long noncoding RNA rhabdomyosarcoma 2 associated transcripts (RMST) in TBI-induced neuroinflammation.

Material and methods: Controlled cortex injury was constructed as an in vivo TBI rat model and lipopolysaccharide (LPS)-induced microglia BV2 was constructed as an in vitro cellular model. Reverse transcription-quantity polymerase chain reaction (RT-qPCR) was employed to detect RMST levels in cerebral cortical tissues and BV2 cells. The modified neurological severity score (mNSS) and Morris water maze test were used to analyze neurological deficits and cognitive dysfunction. Enzyme-linked immunosorbent assay (ELISA) assay and flow cytometry were conducted to examine inflammatory factor levels and apoptosis. Dual luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the target relationship between microRNA (miR)-139-5p and RMST.

Results: RMST was present at high levels in TBI cerebral cortex tissues and LPS-induced BV2 cells, while miR-139-5p was reduced compared with the sham. Silencing RMST alleviated neurological deficits and cognitive dysfunction in TBI rats, but this alleviation was partially eliminated by the reduction of miR-139-5p. Additionally, overactivated neuroinflammatory factors in the TBI cerebral cortex were also suppressed by the knockdown of RMST, but partially restored by reduced miR-139-5p. Finally, the promotion of apoptosis and inflammatory mediator secretion of BV2 by LPS was diminished by silencing of RMST. These effects were all partially attenuated by silencing of miR-139-5p.

Conclusions: RMST can aggravate neuroinflammation and apoptosis in microglia after TBI and thereby affect neurological dysfunction by regulating miR-139-5p.

Collision tumors, a rare phenomenon wherein two tumors with different histological features appear in the same anatomical region, present a challenging clinical diagnosis, particularly in the context of intraspinal collision tumors. This study reports the clinical data of a patient with an intraspinal collision tumor composed of schwannomas and ependymomas. A 47-year-old woman was admitted to the hospital with a six-month history of lumbosacral pain and numbness in both lower extremities. Lumbar magnetic resonance imaging (MRI) revealed two space-occupying lesions in the L1-2 spinal canal, which were initially diagnosed as two separate neurogenic tumors. Subsequent pathological examination revealed a collision tumor comprising a schwannoma and ependymoma. Intraspinal collision tumors, especially those combining schwannoma and ependymocytoma, are exceedingly rare. When two separate or conjoined tumors are present at the same anatomical site, the possibility of a collision tumor should be considered, despite its rarity. Interestingly, it was found that vertebral collision tumors tend to involve hemangiomas, whereas intraspinal collision tumors predominantly involve schwannomas.

Introduction: The present research focused on the function of lncRNA taurine upregulated 1 (TUG1) in a rat neuropathic pain (NP) model constructed by chronic contractile injury (CCI).

Material and methods: Construction of the NP rat model was performed by CCI surgery. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were applied to examine the NP behavior. RT-qPCR was established to explore the levels of TUG1, microRNA (miR)-29b-3p, and HMGB1. ELISA was carried out to evaluate the concentrations of interleukin (IL)-6, IL-1b, tumor necrosis factor a (TNF-a), IL-4, and IL-6. The underlying mechanisms of TUG1 were explored by RNA-binding protein immunoprecipitation (RIP) and dual-luciferase reporter (DLR) assay.

Results: TUG1 and HMGB1 were statistically elevated in the tissue of CCI rats, while miR-29b-3p was reduced. TUG1 competitively binds to miR-29b-3p to upregulate HMGB1 levels. Suppression of TUG1 persistently decreased PWL and PWT along with increased frequency of paw-lifting, whereas this alleviation was typically rescued by the abrogated miR-29b-3p. Analogously, knockdown of TUG1 inhibited CCI-induced overproduction of IL-6, IL-1b, and TNF-a, and reduction of IL-4 and IL-6, but this inhibition was partially abrogated by the reduction of miR-29b-3p.

Conclusions: Suppression TUG1 can alleviate NP hypersensitivity and neuroinflammation in CCI rats by competitively binding miR-29b-3p to weaken HMGB1.

Dysregulations in cholesterol homeostasis contribute to the pathogenesis of multiple sclerosis (MS) and its best described animal model, experimental autoimmune encephalomyelitis (EAE). Cholesterol is an important component of myelin, which is necessary for signal transmission between neurons. Demyelination leads to the formation of oxysterols, degradation products of cholesterol that are ligands for nuclear liver X receptors (LXRs). Genes regulated by LXRs are involved in cholesterol efflux, absorption, transport, and excretion, which we investigated in this study. In this study, we detected changes in gene expression of Srebf1, Ldlr, Soat1, Abca1, Lrp1, and Npc1, all of which are important in the regulation of cholesterol homeostasis, during the course of EAE in male and female rats. In particular, differential expression of Srebf1, Ldlr, and Soat1 was observed in the spinal cord of male and female rats during EAE. Moreover, these genes are altered during EAE. In contrast, the expression of Abca1 and Lrp1 was significantly affected only by sex. In male animals, the expression of Npc1 is conspicuously reduced in EAE pathology. Thus, our study confirms the involvement of enzymes of cholesterol metabolism in the pathophysiology of EAE, with sex and disease progression affecting the expression of these genes. These findings may improve the understanding of neurodegenerative diseases associated with impaired lipid metabolism in the brain, such as MS/EAE.