Neurocysticercosis: An Overview of Pathology and Pathogenesis

Neurocysticercosis (NCC), a subtle parasite infection of the central nervous system, is a powerful example of the complex interaction between human behavior, zoonotic transmission, and neurological illness development. Given the disease’s worldwide prevalence and potentially fatal neurological consequences, research into NCC is critical for advancing knowledge, creating effective diagnostic tools and treatment options, and adopting preventative measures to lessen the disease’s impact. Cysticerci causes an immunological response in the CNS, resulting in inflammation and immune cell recruitment. The existence of intraventricular cysts, cysts in the cerebral aqueduct or fourth ventricle, and the degree of inflammation and scarring induced by the infection are all risk factors for the development of hydrocephalus. This book chapter provides an in-depth exploration of the pathology and pathogenesis of NCC, discussing the life cycle of the Taenia solium parasite, its invasion of the central nervous system, and the formation of cysticerci, as well as the diagnostic challenges and imaging findings, clinical manifestations, and potential neurological complications associated with NCC, serving as a valuable resource for medical professionals, researchers, and policymakers

First description of enhanced expression of glia maturation factor-beta in experimental toxoplasmic encephalitis

PubMed ID: 28774213Objective: We previously showed that Toxoplasma gondii infection induces severe neuropathology in the form of oxidative stress, high nitric oxide production, glial activation, and apoptosis. This study examined the association between glia maturation factor-beta (GMF-ß) expression, activated astrocytes/microglia, and neuropathology in toxoplasmic encephalitis (TE). Methods: Mouse brain GMF expression was examined by immunohistochemistry on days 10 and 30 post-T. gondii infection. Results: Neuropathology of infected mice was associated with increased GMF expression in reactive glial cells and neurons compared with healthy controls. Specific up-regulation of GMF-ß expression in glial cells was associated with increased gliosis in TE. Conclusions: GMF up-regulation in glial cells causes neuronal destruction, suggesting a TE pathological pathway involving GMF-mediated brain cell cytotoxicity. GMF-ß may therefore be a good biomarker for disease risk assessment and to estimate host neuropathy after exposure to T. gondii, as well as providing a new therapeutic target. This is the first study to demonstrate the expression of GMF-ß in reactive glial cells and its association with neuropathology in TE. © 2017, © The Author(s) 2017

Sınır hastalığı virüsü ile doğal enfekte kuzu ve oğlak beyinlerinde apoptotik ve anti-apoptotik mekanizmaların karşılıklı değerlendirilmesi

Tez (Doktora) -- Kırıkkale Üniversitesi89951

Evaluation of apoptotic and anti-apoptotic mechanisms in sheep and goat brains naturally infected with border disease virus

YÖK Tez ID: 331471Sınır Hastalığı (SH) Türkiye dahil, dünyada koyun ve keçi popülasyonlarında abortus veya persiste enfeksiyonlar nedeniyle ülke ekonomisinde ciddi kayıplara neden olan ve Pestivirüsler tarafından oluşturulan viral bir hastalıktır. Hücre kültüründeki sitopatojenitelerine göre Pestivirüsler, apoptotik hücre ölümünü tetikleyen sitopatik (SP) ve sitopatik olmayan (SPO) tür olarak ikiye ayrılırlar. Sitopatik olmayan türler enfekte ettiği hücrelerde apoptozisi engelleyici etki göstererek persiste enfeksiyondan sorumludur. Sınır Hastalığı Virüsü'nün (SHV) apoptotik ve anti-apoptotik mekanizmalarının merkezi sinir sisteminde araştırıldığı sınırlı sayıda çalışma vardır. Bu çalışmada, SHV enfekte kuzu ve oğlaklarda; apoptotik ve anti-apoptotik mekanizmaların karşılıklı araştırılması ve eğer varsa SHV'nin merkezi sinir sisteminde hangi yolakla apoptozisi tetiklediğinin ortaya konulması amaçlanmıştır. Bu amaçla da; SHV ile enfekte hayvanların beyin kökü ve orta beyin bölgesinde meydana gelen lezyonlarda; apoptotik (kaspaz 3, kaspaz 9) ve anti-apoptotik (Bcl-2) mekanizmalar, sitokin yanıtı (TNFR1, TNF-?, INF-?, eNOS ve iNOS), apoptotik hücre sayılarının tespiti (TUNEL), reaktif gliozis (GFAP), myelin hasarı (LFB) incelenerek sağlıklı kontrol dokuları ile karşılaştırılmıştır. Çalışmanın materyalini, moleküler ve immunoperoksidaz testlerle SH tanısı konulan 10 kuzu, 5 oğlak ve sağlıklı kontrol için ise sağlıklı 3 kuzu ve 3 oğlaktan alınan beyin dokuları oluşturmuştur. Parafine gömülen dokulardan alınan 5 ?m kalınlığındaki kesitler, hematoksilen-eozin ile boyandıktan sonra histopatolojik incelemede, nöron dejenerasyon ve nekrozu, gliozis, myelin kaybı, perivasküler hücre infiltrasyonu ve vaskülit bulguları dikkate alınarak lezyon şiddetine göre skorlandı. Bu çalışmada, SHV pozitif hayvanlardaki beyin kökü ve orta beyin bölgelerinden alınan kesitlerde; indirekt immunoperoksidaz testlerde tavşan-anti SHV poliklonal antikoru ve ticari firmalardan temin edilen apoptotik ve anti-apoptotik mekanizmaların tanımlanmasında rabbit poliklonal kaspaz 3, 9, Bcl-2, TNFR1, TNF-? ve INF- ?, TUNEL, GFAP, eNOS, iNOS antikorları ve myelin hasarı tespiti için histokimyasal boyama olarak da LFB kullanıldı. İmmunoperoksidaz test sonuçlarına göre; kaspaz 9, Bcl-2, TUNEL, GFAP, eNOS ve iNOS immunopozitif boyanma yüzde alanları, kontrol grubu hayvanlardakine oranla istatistiksel olarak önemli (p0.05). Deney grubu hayvanlarda, enfeksiyonun şiddetinde artışla birlikte myelin kaybı ve reaktif glia hücrelerinde GFAP varlığının arttığı görülmüştür. Sınır Hastalığı Virüsü ile enfekte çalışma grubu hayvanlar ile sağlıklı kontrol grubu hayvanların karşılaştırılması sonucunda; en çarpıcı bulgu beyinde eNOS ve iNOS varlığının hastalığın şiddeti ile doğru orantılı artmasıdır ve bunun SHV enfeksiyonunda şekillenen apoptozis belirteçleri ile uyumlu olduğu gösterilmiştir. Aynı zamanda, SHV ile enfekte hücreler arasında apoptozise giden hücrelerin baskın olarak içsel yolu seçtikleri ve içsel yol üzerine de en büyük etkinin önemli derecede artan NO seviyesi ile ilişkili olabileceği ortaya konulmuştur. Deney grubu hayvanlarda görülen myelin kaybı ile GFAP varlığı sonuçlarına göre; enfeksiyonun şiddeti arttıkça dejenerasyon derecesinin de paralel olarak arttığı görülmüştür.Border Disease is viral disease caused by Pestiviruses and has commonly been reported worldwide including Turkey. The disease creates a serious economic problem due to abortion and persistent infections in sheep and goats. Based on pathogenicity to cell culture, Pestiviruses are categorized into two classes: cytopathic (CP) and non-cytopathic, which have generally apoptotic and anti-apoptotic effects, respectively. Non-cytopathic viruses are responsible for persistent infections as they exert an anti-apoptotic effect in Pestivirus infected cells. There is limited number of studies focusing on the apoptotic and anti-apoptotic mechanisms in the central nervous system targeted by Border Disease Virus (BDV). In this study, investigation of comparision of apoptotic and anti-apoptotic mechanism and which pathway to trigger the apoptosis in cental nervous system in BDV infected lamb and kid was aimed. In BDV infected lesioned brain stem and mid brain regions, apoptotic (caspase 3 and caspase 9) and anti-apoptotic (Bcl-2) mechanisms, cytokine response (TNFR1, TNF-?, INF-?, eNOS, and iNOS), number of apoptotic cells (TUNEL), reactive gliosis (GFAP), myelin loss (Luxol Fast Blue-LFB) were examined and compared to control healthy tissues. The study materials included in the study were brain tissues collected form BDV diagnosed 10 sheep and 5 goats as well as control brain tissues from 3 lambs and 3 goat kids. Following sectioning from the paraffin embedded tissue, the 5 µm thick sections were stained with hematoxylin-eosin and examined histopathologically and scored according to presence and severity of neuron regenerations and necrosis, gliosis, myelin loss, perivascular cell infiltrations, and vasculitis. In BDV positive brain stem, cerebellum and mid-brain tissue sections, a rabbit polyclonal BDV antibody commercial and rabbit polyclonal anti caspase 3, caspase 9, Bcl-2, TNFR1, TNF-?, INF-?, eNOS, iNOS, and GFAP antibodies were employed. Number of apoptotic cells was determined by TUNEL method and myelin loss was determined histochemically by LFB staining. According to immunoperoxidase test results, the percent area of caspase 9, Bcl-2, TUNEL, GFAP, eNOS and iNOS immunopositive staining was higher in BDV infected tissues compared to control (p0.05). There was a consistency between the intensity of regenerations based on the score of myelin loss and GFAP tests and severity of infection. As a results, the most remarkable result was that the brain eNOS and iNOS expressions is positively correlated with the severity of the disease that is compatible with the expression of apoptotic markers in BDV infections. The results also indicated that among the BDV infected cells, apoptotic cells mainly prefer the intrinsic pathway and the highest effect on the intrinsic pathway is most likely related to nitric oxide levels

Pathologic Apoptosis And Diagnostic Methods

İlk kez Kerr ve arkadaşları tarafından 1972 de tanımlanan apoptozis, biyolojik görevlerini tamamlamışyapısal elemanları ya da DNA’sı hasar görmüş hücrelerin, ilişkili olduğu doku ve hücrelere zarar vermeyecek birbiçimde ortadan kaldırılmasını sağlayan, genlerle kontrol altında tutulan ve gerçekleşmesi için enerjiye ihtiyaçduyan programlı hücre ölümüdür. Apoptozisi fizyolojik olarak yaşamın her dönemimde görebiliriz. Patolojikapoptozis ise otoimmün ve nörodejeneratif hastalıklar, kanser, kalp hastalıkları ve viral enfeksiyonlar gibi birçokhastalığın patogenezinde yakından ilişkilidir. Apoptozis emri alan bir hücrede kromatin yoğunlaşması görülür vehücrenin boyutları küçülmeye başlar. Daha sonra apoptotik cisimciklere ayrılırlar. Bu apoptotik cisimcikleryüzeylerinde yeni reseptörlerle birlikte yakındaki fagositik sistem hücrelerini çağırarak fagotositoz ileuzaklaştırılır. Apoptozisin inhibisyonu/aktivasyonu tedavi için gen ürünleri ise tanı için potansiyel hedeflerdir.Bu makale; apoptozisin morfolojik özelliklerini ve nekrozdan farklarını, genetik düzenlenmesini, tanıyöntemlerini ve özellikle hastalıklardaki yakın ilişkisini içeren son literatür bilgileri gözden geçirilerektartışılmış bir derlemedir.First defined by Kerr et al. in 1972, the apoptosis is the programmed cell death which is kept undercontrol by genes and needs energy to occur, allowing structural elements with completed biological duties orcells with damaged DNA to be removed without damaging the associated tissue and cells. Apoptosis can be seenphysiologically in all stages of life. Pathological apoptosis is closely related in the pathogenesis many diseases,including autoimmune and neurodegenerative diseases, cancer, heart diseases and viral infections. Chromatincondensation is observed and the size of cell becomes smaller in a cell that receives the apoptosis order. Thenthey are fragmented into apoptotic bodies. These apoptotic bodies are removed by phagocytosis by callingnearby phagocytic system cells together with new receptors on their surfaces. Inhibition/activation of apoptosisand gene products are potential targets for treatment and diagnosis, respectively. This article is a compilation thatdiscusses morphologic characteristics of apoptosis, its differences from necrosis, genetic regulation, diagnosismethods and close association with diseases by reviewing the latest literature

Overexpression of ADAMTS-13 and neuronal nitric oxide synthase relates with neuropathology in streptozotocin-induced type 1 diabetic rats

Hyperglycemia plays a critical role in the development and progression of diabetic encephalopathy. A few studies have focused on a disintegrin and metalloprotease with thrombospondin type I repeats-13 (ADAMTS-13) expression in the central nervous system (CNS), and its function continues to remain unclear. The purpose of this study was to compare the expression of ADAMTS-13, neuron specific enolase (NSE), neurofilament (NF), neuronal nitric oxide synthase (nNOS) and glial fibrillary acidic protein (GFAP) in brain tissues of experimental streptozotocin (STZ)-induced diabetic rats. Expression of ADAMTS-13 (P < 0.001), nNOS (P < 0.001), NSE (P < 0.001) and NF (P < 0.001) expressions in the brain tissue markedly increased while GFAP decreased (P < 0.001) in diabetic animals versus controls. The most prominent finding of our study was that ADAMTS-13 expression increased significantly, suggesting that it may play an important function/s in the regulation and protection of the blood-brain barrier integrity and central nervous system microenvironment in diabetes. The results also suggested that nitric oxide production may increase due to increased nNOS expression and this also might contribute to neuropathology related with diabetes. Furthermore, increased expression of ADAMTS-13, NSE, NF and decreased expression of GFAP may give an idea of the disease progress and thus may have a critical diagnostic significance. To the best of the authors' knowledge, this is the first report on ADAMTS-13 expression in the CNS of STZ-induced diabetic animals

The effect of Pneumonic Pasteurellosis on Apoptosis and Nitric Oxide Synthase in the Lungs in Calves

Pneumonic Pasteurellosis (PP) is an infectious disease caused by Pasteurella multocida and Mannheimia haemolytica, mostly observed in cattle, sheep and calves. PP is characterized by fibrinous bronchopneumonia and pleuritis in the lungs. In this study, it was aimed to determine Caspase-3, Caspase-9, inducible nitric oxide synthase and neuronal nitric oxide synthase expressions by immunohistochemical methods in the lungs suffered from PP. For this purpose, twenty lung tissues were collected from calves with PP. For the Control Group, ten lungs of calves were collected from Aksaray Slaughterhouse. After necropsies of calves were confirmed to be PP by bacteriological examinations. Then the routine histological process was performed to tissues, and stained by Hematoxylin & Eosin for histopathology, and Caspase-3, Caspase-9, inducible nitric oxide synthase and neuronal nitric oxide synthase antibody staining for immunohistochemistry. The immunohistochemical findings indicated that Caspase-3, Caspase-9, inducible nitric oxide synthase and neuronal nitric oxide synthase positive reactions were seen in alveolar, bronchial and bronchiolar epithelia, and desquamated inflammatory cells in the lumens. In addition, the peripheral neural extensions were immunopositive for neuronal nitric oxide synthase and vascular endothelial cell were positive for inducible nitric oxide synthase. The findings can contribute to a better understanding of expressions of molecules such as Caspase and nitric oxide synthase. These results show that apoptosis and nitric oxide synthase expressions have triggered by airway epithelia and inflammatory cells in the lungs with Pneumonic Pasteurellosis in calves

First description of enhanced expression of transforming growth factor-alpha (TGF-?) and glia maturation factor-beta (GMF-ß) correlate with severity of neuropathology in border disease virus-infected small ruminants

PubMed ID: 30654008Border disease (BD) is caused by Pestivirus and characterized by severe neuropathology, and histopathologically observed severe hypomyelination. We have previously shown that small ruminants infected with border disease virus (BDV) play an important role for neuropathology and pathogenesis of severe oxidative damage in brain tissue, neuronal mtDNA; in the production of high pathologic levels of nitric oxide; in glial cell activation and stimulation of intrinsic apoptosis pathway. This study aimed to investigate the relationship between glia maturation factor beta (GMF-ß) and transforming growth factor alpha (TGF-?) expressions and the causes of BDV-induced neuropathology and to investigate their role in neuropathogenesis in a way that was not presented before. Expression levels of GMF-ß and TGF-? were investigated. Results of the study revealed that the levels of GMF-ß (P < 0.005) and TGF-? (P < 0.005) expression in the brain tissue markedly increased in the BDV-infected animals compared to the non-infected healthy control group. While TGF-? expressions were predominantly observed in neurons, GMF-ß expressions were found in astrocytes, glial cells and neurons. These results were reasonable to suggest that BDV-mediated increased GMF-ß might play a pivotal role neuropathogenesis and a different type of role in the mechanism of neurodegeneration/neuropathology in the process of BD. The results also indicated that increased levels of GMF up-regulation in glial cells and neurons causes neuronal destruction, suggesting pathological pathway involving GMF-mediated brain cell cytotoxicity. It is clearly indicated that the cause of astrogliosis is due to severe TGF-a expression. This is the first study to demonstrate the expression of GMF-ß and TGF-? in neurons and reactive glial cells and its association with neuropathology in BD. © 2019 Elsevier Lt