Folia neuropathologica最新文献

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.

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.

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.

Introduction: Alzheimer's disease (AD) is classified as a neurodegenerative disorder without efficacious therapeutic interventions. Accumulating evidence has demonstrated the deposition of b-amyloid peptide (Ab) in the spinal cord in several mouse AD models. Neuregulin 2 (Nrg2), structurally homologous to neuregulin 1 (Nrg1), exerts a regulatory influence over various biological processes within the nervous system. However, the neuroprotective role of Nrg2 in the spinal cord in AD remains unclear.

Material and methods: Reverse transcription PCR (RT-PCR) was employed to confirm the expression of mutated amyloid precursor protein (APP) in APPswe mice. Immunohistochemical staining was used to compare the differences between wild-type and APPswe mice in APP and GFAP expression. We applied western blot to test the changes of ErbB4, Akt1, and Erk1/2 activation, as well as that of GFAP in response to recombinant Nrg2 (rNrg2) treatment in the spinal cord in APPswe mice.

Results: In the current study, we observed that mutated APP mRNA level was upregulated, and astrocytes were activated in the spinal cord of APPswe transgenic mice. rNrg2 treatment down-regulated astrocyte activation, as indicated by the reduced level of GFAP. Meanwhile, Nrg2 treatment enhanced the phosphorylation-mediated activation of ErbB4, Akt1, and Erk1/2 in most of the spinal cord segments.

Conclusions: These combined results suggest the involvement of astrocytosis in the spinal cord of APPswe transgenic mice. Neuregulin 2, when administered exogenously, may represent a potential strategy for preventing and treating AD-induced astrocytosis in the spinal cord.

Introduction: Intervertebral discs are generally known as the body's largest avascular structures. In the human body, there is not yet a collective resource characterizing intervertebral vascularization. When an intervertebral disc herniation occurs, new blood vessels proliferate in the capsule of the herniated tissue. In this study, we aimed to investigate intervertebral disc degeneration, neovascularization, and histopathological findings in patients who underwent surgical treatment.

Material and methods: The study was carried out by retrospective, double-blind examination of lumbar intervertebral disc tissue removed during the operation of 72 patients. To observe the structure of the disc, 5-6-micron-thick sections were taken, stained with hematoxylin and eosin (HE), and neovascularization and angiogenesis in the degenerated intervertebral disc tissue were examined microscopically.

Results: The results showed that neovascularization and bleeding measurements were not independent from each other, and there was a statistically significant association between them. Also, a higher level of neovascularization was found to be associated with higher bleeding and higher mononuclear inflammation.

Conclusions: With the development of degeneration in the intervertebral disc tissue, angiogenesis, neovascularization and mononuclear cell migration occur. It is predicted that proinflammatory cytokines cooperate with angiogenesis and mononuclear cells in the development of degeneration. There is currently no treatment to prevent intervertebral disc degeneration. In order to develop successful treatments to prevent this disease, its pathogenesis needs to be understood.

This study assessed the effect of batatasin-III on cerebral microvascular endothelial cell (EC) injury. Endothelial cell injury was induced in isolated cells by oxygenglucose deprivation/reperfusion (OGD/R) conditions. During 4 h of OGD insult, cells were treated with batatasin-III at different concentrations, and an MTT assay was performed to estimate cellular viability. Nitric oxide, mitochondrial membrane potential (MMP), and release of lactate dehydrogenase (LDH) were determined in ECs exposed to OGD/R. Cerebral ischemia was performed to induce brain injury to assesses the effect of batatasin-III. There was improvement in the viability of cell and reduction of release of LDH in batatasin-III-treated, OGD/R-induced EC injury. Treatment with batatasin-III ameliorates the altered integrity of mitochondrial membrane and expression of apoptotic proteins in OGD/R injured ECs. Apoptosis of neuronal cells and infarct size were reduced in batatasin-III-treated middle cerebral artery occlusion (MCAO) rats, and pathological changes were reversed. Based on study data, we concluded that cerebral injury was attenuated by batatasin-III treatment by reducing oxidative stress and cellular apoptosis.

Introduction: Stathmin, recognised as the protein associated with the disassembly of microtubules, plays a vital role in the modulation of human fear as well as anxiety responses. However, it is unclear whether stathmin regulates the specific mechanism of disruption of fear-associated memory resulting from posttraumatic stress disorder (PTSD). This study aims to observe the impact of stathmin on deficit in fear-based memory during PTSD and investigate the underlying mechanisms involved, in order to establish an empirical foundation for elucidating the molecular mechanisms underlying the pathogenesis of PTSD.

Material and methods: We used an single prolonged stress (SPS) protocol to induce the PTSD in the rat model. Open field test and forced swimming test were used to examine the anxious and fearful behaviours exhibited by the rats. STAT3/stathmin signalling-related expressions were assessed through immunofluorescence, immunohistochemical, RT-qPCR and Western blotting. Stathmin and STAT3 binding activity was detected by molecular docking. Amygdala apoptosis was detected by TUNEL staining.

Results: In this study, while stathmin gene expression in amygdala was significantly downregulated, after 7 days of SPS, activation of STAT3 was observed in the rats' amygdala, accompanied by a notable increase in the apoptosis rate. Consequently, the rats exhibited heightened fear and anxiety responses. However, the above results were reversed after overexpression of the stathmin gene. In addition, following the administration of the STAT3 inhibitor, WP1066, there was a notable reduction in the apoptosis rate, leading to decreased levels of fear and anxiety in rats exposed to SPS. In rats exposed to SPS, administered WP1066, and injected with adenovirus expressing stathmin-targeted siRNA into the amygdala to make the inhibition of stathmin expression partially counteracted the protective effect of WP1066.

Conclusions: The findings above suggest that SPS could potentially modulate the stathmin gene's expression by activating the STAT3 pathway, subsequently leading to apoptosis in amygdala cells. This sequence of events ultimately contributes to the PTSD rat model fear memory impairment.