Folia neuropathologica最新文献

Paclitaxel (PTX) is a potent chemotherapy drug commonly used to treat various solid tumours, including breast and ovarian cancers. However, its effectiveness in treating IDH-wildtype glioblastoma has been limited due to challenges crossing the blood-brain barrier (BBB). Glioblastoma remains one of the most difficult cancers to treat, with a median survival of 15 months from diagnosis. Recent advancements in nanotechnology have led to innovative PTX delivery systems that enhance its bioavailability and enable targeted brain therapy. These include nanoparticles composed of biocompatible materials that enhance drug solubility and targeting while addressing BBB permeability. Examples include albumin-bound PTX (Abraxane), self-assembled nanoparticles from natural bioactive molecules, poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles, and hydrophilic nano-prodrugs, each showing promise in enhancing the therapeutic impact of PTX. These systems utilize biocompatible nanoparticles that enhance drug solubility, targeting, and BBB permeability. Numerous ongoing clinical trials and preclinical studies are exploring the efficacy of these nanocarrier systems in overcoming drug resistance and improving patient outcomes. The latest advancements in PTX-based nanotherapeutics for glioblastoma focus on overcoming the BBB, developing nanoparticle delivery systems, and evaluating the clinical significance of these developments.

Anatomical studies of the brain and successive analyses of this organ were performed in ancient times. Indeed, notes found in the Edwin Smith Papyrus mention that the Egyptians identified the meninges and gyri millennia ago. Their successors examined the content of the skull, examined it and illustrated it in greater detail. Alexandrians (Herophilus and Erasistratus) described the cerebral ventricles and blood circulation and supply to the brain. More accurate depictions emerged during the Renaissance with Leonardo da Vinci (1452-1519), Charles Estienne (1504-1564) and Andreas Vesalius (1514-1564), followed by Thomas Bartholin (1616-1680), Franciscus Sylvius (1614-1672) and later scholars. The present study focuses on neuroanatomy and is devoted to the study of nervous system structures by the eminent pathologist Rudolph Virchow. When reorganizing the procedure and reporting of the post-mortem examination, including a meticulous autopsy of the brain, neuropathology was a discipline yet to be developed. He pioneered a new approach to the autopsy and analysis of its results, aiming to benefit not only the patients but also clinicians and pathologists.

Introduction: A molecular sequencing and phenotyping study was conducted on chemokines CCL2, CCL5, and CXCL10 to assess the relation to multiple sclerosis (MS).

Material and methods: The molecular detection study included extractions of DNA from the blood of cases and a control group, as well as amplification and confirmation of all extracted DNA. The 490-bp primer-size PCR product corresponded to CCL2, the 481-bp primer-size PCR product corresponded to CCL5, and the 310-bp primer-size PCR product corresponded to CXCL10.

Results: DNA sequencing of CCL2, CCL5, and CXCL10 showed that there was convergence between the obtained results and data from the GenBank database (NCBI) with 99% identity (439/445) in the forward CCL2 sequence, which had a single transition mutation, GGT to GGG. In addition, the reverse CCL2 showed 99% identity (426/427) when compared with the GenBank database (NCBI), which found a single deletion mutation, TGA to GGG. There was convergence between the studied CCL5 isolated and that of the GenBank database (NCBI) with 99% identity (443/447) in the forward CCL5. Four mutations were recorded: three transversions - TTT to TTA, AAA to AAT, and GCC to GCA - and one deletion, TGA to TGG. On the other hand, the reverse CCL2 showed 99% identity (436/439) when compared with the GenBank database (NCBI), with three mutations: two deletions - TGA to TG-, and CCA to CC- - and one transversion, ATT to ATA. Also, there was convergence between the studied CXCL10 isolated and that of the GenBank database (NCBI), with 98% identity 64/65 in the forward CXCL10 and one transversion mutation, GGT to GGG.

Conclusions: New genes for the chemokines CCL2, CCL5 and CXCL10 have been recorded. The results were registered in the NCBI database under accession numbers LC727557, LC727558, and LC727558, respectively. The study revealed the important roles of chemokines in the pathogenesis of MS, suggesting their potential as targets for future therapy.

Introduction: Malignant tumours diagnosed in the central nervous system are among the leading causes of death from cancer. Central nervous system tumours are the 10th most frequent cause of mortality due to cancer. Immunohistochemistry has become an important tool in the diagnosis of brain tumours. Brain tissue and meninges tumours comprise a heterogeneous group with diverse biological behaviour, treatment management, and different prognoses. Although conventional haematoxylin-eosin staining is crucial for diagnosis, diagnostic neuropathology has benefited from the inclusion of immunohistochemistry and recent advances in the field over the past 20 years. GFAP, S100, IDH, OLIG 2, EMA, ATRX, P53 and Ki67 are the most frequently used immunohistochemical markers globally, which we also highlighted in our study.

Material and methods: Ninety-seven cases including primary-metastatic intracranial tumours, operated on in the Neurosurgery Clinic and diagnosed in the Medical Pathology Laboratory between 2018 and 2023 years, were examined retrospectively from the archive. Haematoxylin-eosin slides were re-evaluated under the light microscope by 2 double-blind pathologists and immunohistochemical features and characteristics of tumours were examined. Data were analysed using the program SPSS 22. Differences were accepted as statistically significant at p < 0.05.

Results: According to the analysis of results, 46 (47.4%) of the 97 included patients were female and 51 (52.6%) were male. The most common tumour types were meningioma with 31 (32%) and high-grade neuroglial tumours with 31 (32%). GFAP, OLIG2, ATRX, and P53 values were found to be significantly higher in high-grade neuroglial tumours. While S 100 and EMA values were especially high in meningiomas, a positive correlation was found with IDH value in low-grade neuroglial tumours. The study showed that the median Ki67 value was significantly higher in high-grade neuroglial tumours and metastatic tumours.

Conclusions: Intracranial tumours cause significant morbidity and mortality in patients. Diagnostic, prognostic and predictive biomarkers evaluated in patient biopsy specimens and/or body fluids are important in neuropathological oncology. By regularly updating our biomarkers and following new treatment approaches, we can improve survival with rapid diagnosis and appropriate treatment in central nervous system tumours after surgery.

Introduction: The nucleotide-binding domain leucine-rich repeat-containing family pyrin domain-containing 3 (NLRP3) inflammasome has been implicated in numerous neurological disorders, including epilepsy, through its role in inflammation and pyroptosis. Dihydromyricetin (DHM) has neuroprotective effects in patients with neurological disorders. However, the impact of DHM on the NLRP3 inflammasome pathway in epilepsy and related cognitive impairment is yet to be fully understood. Herein, we evaluated whether DHM can alleviate pilocarpine-induced neuronal injury and learning and memory disorders in the hippocampal body of rats by regulating the NLRP3 inflammasome.

Material and methods: An epileptic rat model was established, and spontaneous recurrent seizure (SRS) frequency and duration were recorded. The function of hippocampal pyramidal neurons was evaluated using Nissl staining. Western blotting, real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to detect changes in NLRP3 inflammatory pathway-related factors in the hippocampus. Cognitive function was verified using the Morris water maze test, hippocampal late-phase long-term potentiation recording and associated synaptic protein expression assessment.

Results: Treatment with DHM after status epilepticus (SE) induction decreases the frequency and length of SRS in rats receiving pilocarpine, suggesting that DHM has the potential to improve long-term potentiation and cognitive deficits after SE induction in rats. Additionally, after inducing SE in rats, DHM raises the expression of synaptic proteins. It may prevent harm to hippocampal pyramidal neurons, and DHM-induced neuroprotection may contribute to the pyroptosis associated with NLRP3 in epileptic rats. DHM guards against harm to hippocampus pyramidal neurons.

Conclusions: We found that DHM plays a role in treating epilepsy and its comorbid cognitive impairment by inhibiting pyroptosis and inflammation.

Autoimmune diseases (AID) such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory neuropathies, and some 100 other conditions, affect 5-10% of the global population, and their incidence is increasing, particularly in women. Among these, myasthenia gravis (MG) is a relatively rare but debilitating disease, which represents a prototype antibody-mediated autoimmune condition with well-studied pathogenesis. MG is a neuromuscular junction disorder marked clinically by fatigable muscle weakness and serologically by the presence of pathogenic autoantibodies. In MG pathological B- and T-cell subtypes are implicated, including memory B and plasma cells. In recent years there has been significant progress in the field of therapy, with several novel drugs introduced targeting major components of the pathogenetic pathway. However, there are still unmet needs in the treatment, especially the lack of a curative, upstream approach in contrast to the existing chronic downstream immunomodulatory actions. A nucleoside analog cladribine was primarily developed for the treatment of chronic leukaemias, in particular hairy cell leukaemia. For these indications, the injectable formulation of the drug was registered in 1997, and it has been manufactured in several countries since then. Later the oral formulation of cladribine (Mavenclad, Merck KGaA) was registered worldwide for use as immune reconstitution therapy (IRT) for relapsing multiple sclerosis. In this setting it has gained a strong position in the group of high-efficacy compounds, exerting long-term impact on the immune system. In a pilot clinical study, we found appreciable efficacy and safety profile of a short course of cladribine in MG. Herein, we present the design of a prospective, multicentre, randomised, controlled trial (RCT) using a parenteral preparation of cladribine in MG, currently ongoing in 6 clinical centres in Poland (EudraCT No. 2020-005762-34). In addition, we discuss the concept of immune reconstitution, which seems applicable for MG treatment.