Brain Cysts Research Articles

Hyperacute brain cyst after deep brain stimulation surgery: a case with complete spontaneous resolution.

Hyperacute brain cyst after deep brain stimulation surgery: a case with complete spontaneous resolution.

Heterologous immunization targeting the CST1 antigen confers better protection than ROP18 in mice.

Aim: To evaluate the protective efficacy induced by heterologous immunization with recombinant baculoviruses or virus-like particles targeting the CST1 and ROP18 antigens of Toxoplasma gondii.Materials & methods: Recombinant baculovirus and virus-like particle vaccines expressing T. gondii CST1 or ROP18 antigens were developed to evaluate protective immunity in mice upon challenge infection with 450 Toxoplasma gondii (ME49).Results: Immunization with CST1 or ROP18 vaccines induced similar levels of T. gondii-specific IgG and IgA responses. Compared with ROP 18, CST1 vaccine showed better antibody-secreting cell response, germinal center B cell activation, and significantly reduced brain cyst burden and body weight loss.Conclusion: Our findings suggest that CST1 heterologous immunization elicited better protection than ROP18, providing important insight into improving the toxoplasmosis vaccine design strategy.

Live-attenuated PruΔgra72 strain of Toxoplasma gondii induces strong protective immunity against acute and chronic toxoplasmosis in mice

BackgroundToxoplasma gondii is an intracellular opportunistic pathogenic protozoan that poses serious threats, particularly in immunocompromised individuals. In the absence of a robust prophylactic measure, the mitigation and management of toxoplasmosis present formidable challenges to public health. We recently found that GRA72 plays an important role in parasitophorous vacuole (PV) morphology, growth and virulence of T. gondii. However, whether gra72-deficient strain can be used as a vaccine remains unknown.MethodsWe first examined the attenuated virulence of gra72 gene knockout strain (PruΔgra72) and the parasite load in organs of the infected mice. Subsequently, we evaluated the immune-protective effects of the PruΔgra72 vaccination against challenge with various types of T. gondii tachyzoites and Pru cysts. Furthermore, levels of antibodies and cytokines induced by PruΔgra72 vaccination were examined. Statistical analysis was conducted by Student’s t-test or Mantel-Cox log-rank test based on data obtained from three independent experiments with GraphPad Prism 8.0.ResultsWe found that PruΔgra72 strain exhibited a significantly attenuated virulence even at the highest dose of 5 × 107 tachyzoites in Kunming mice model. The significant decrease of brain cyst burden and parasite load in the organs of the PruΔgra72-infected mice suggested its potentiality as a live-attenuated vaccine. Hence, we explored the protective immunity of PruΔgra72 vaccination against toxoplasmosis. Results showed that vaccination with 5 × 106 PruΔgra72 tachyzoites triggered a strong and sustained Th1-biased immune response, marked by significantly increased levels of anti-T. gondii IgG antibodies, and significantly higher levels of Th1 type cytokines (IL-2, IL-12 and IFN-γ) compared to that of Th2 type (IL-4 and IL-10). Vaccination with 5 × 106 PruΔgra72 tachyzoites in mice conferred long-term protection against T. gondii infection by less virulent tachyzoites (ToxoDB#9 PYS and Pru strains) and Pru cysts, provided partial protection against acute infection by high virulent Type I RH tachyzoites and significantly decreased brain cyst burden of chronically infected mice.ConclusionsThe avirulent PruΔgra72 induced strong protective immunity against acute and chronic T. gondii infection and is a promising candidate for developing a safe and effective live-attenuated vaccine against T. gondii infection.Graphical

Effectiveness of Miltefosine Nanoemulsion Concerning the Treatment of Acute and Chronic Toxoplasmosis: In Vivo Study.

Toxoplasma gondii is one of the most common parasites worldwide. It is of great importance to identify new potential drugs that are effective and less harmful in pregnant women and newborns. We investigated nanoemulsion miltefosine (NEM) in treating experimental acute and chronic toxoplasmosis. A combination of triacetin, Tween 80, and ethanol (1:2) was used for the development of NEM formulations. The size of NEM was calculated to be 17.463 nm by DLS and TEM. To investigate the performance of miltefosine (MLF), NEM, sulfadiazine (SDZ), and pyrimethamine (PYR) (positive control) in vivo, acute toxoplasmosis was induced in mice by an intraperitoneal injection of RH strain tachyzoites. After five days, the mice were examined for the number and condition of tachyzoites and histopathological changes in the liver and spleen. Chronic toxoplasmosis was investigated in rats and the number and size of brain cysts along with histopathological changes were assessed in different groups. The results of the in vivo assessment of drugs in acute toxoplasmosis showed the following order regarding a decrease in the number of tachyzoites and an increase in survival rate: SDZ&PYR > NEM > MLF. The effects of drugs on chronic toxoplasmosis showed a significant effect of NEM (50%) on reducing the number of cysts compared to SDZ&PYR (10%) and MLF (12%) and reducing the size of NEM brain cysts (21%) compared to SDZ&PYR (5 %) and MLF (8%). Increasing the penetration of NEM through the blood-brain barrier (BBB) and subsequently reducing the number and size of T. gondii tissue cysts is a promising new drug in treating chronic toxoplasmosis.

Evaluating the modulation of peripheral immune profile in people living with HIV and (Neuro)cysticercosis.

The parasitic infection caused by Taenia solium represents a significant public health concern in developing countries. Larval invasion of body tissues leads to cysticercosis (CC), while central nervous system (CNS) involvement results in neurocysticercosis (NCC). Both conditions exhibit diverse clinical manifestations, and the potential impact of concomitant HIV infection especially prevalent in sub-Saharan Africa on peripheral and CNS immune responses remains poorly understood. This study aimed to identify the potential impact of HIV coinfection in CC and NCC patients. A nested study within a cross-sectional analysis in two Tanzanian regions was performed and 234 participants (110 HIV+ and 124 HIV-) were tested for cysticercosis antibodies, antigens, CD4 counts and serum Th1 and Th2 cytokines via multiplex bead-based immunoassay. 127 cysticercosis seropositive individuals underwent cranial computed tomography (CCT) and clinical symptoms were assessed. Multiple regression analyses were performed to identify factors associated with cytokine modulation due to HIV in CC and NCC patients. Serologically, 18.8% tested positive for cysticercosis antibodies, with no significant difference HIV+ and HIV+. A significantly higher rate of cysticercosis antigen positivity was found in HIV+ individuals (43.6%) compared to HIV- (28.2%) (p = 0.016). CCT scans revealed that overall 10.3% had active brain cysts (NCC+). Our study found no significant changes in the overall cytokine profiles between HIV+ and HIV- participants coinfected CC and NCC, except for IL-5 which was elevated in HIV+ individuals with cysticercosis. Furthermore, HIV infection in general was associated with increased levels of pro-and some anti-inflammatory cytokines e.g. TNF-α, IL-8, and IFN-γ. However, based on the interaction analyses, no cytokine changes were observed due to HIV in CC or NCC patients. In conclusion, while HIV infection itself significantly modulates levels of key cytokines such as TNF-α, IL-8, and IFN-γ, it does not modulate any cytokine changes due to CC or NCC. This underscores the dominant influence of HIV on the immune system and highlights the importance of effective antiretroviral therapy in managing immune responses in individuals coinfected with HIV and CC/NCC.

Electroconvulsive Therapy With Brain Cyst: A Simulation Study.

Electroconvulsive therapy (ECT) is effective in treating severe depression and other neuropsychiatric disorders, but how the presence of an anatomical anomaly affects the electrical pathways between the electrodes remains unclear. We investigate the difference in electric field (E-field) distribution during ECT in the brain of a patient with an arachnoid cyst relative to hypothetical condition where the cyst was not present. Magnetic resonance imaging scans of the head of a patient with a large left frontal cyst were segmented to construct a finite element model to study the E-field distribution during ECT. Five electrode configurations were investigated: right unilateral, left unilateral, bifrontal, and bitemporal and left anterior right temporal. The E-field distributions for all montages were compared with a hypothetical condition where brain tissue and electrical conductivity from the right frontal region was mirrored across the longitudinal fissure into the cyst. Differences in mean E-field and 90th percentile E-fields were mainly observed in brain regions closest to the cyst including the left inferior frontal gyrus and left middle frontal gyrus. This trend was most pronounced in montages where the electrodes were closest to the cyst such as left unilateral and bitemporal. The presence of a highly conductive cyst close to the ECT electrode tended to attract current into the cyst region, altering current pathways, with potential implications for therapeutic efficacy and safety. Placing electrodes farther away from the cyst is likely to minimize any effects on the E-field distribution and potentially clinical outcomes.

Spiramycin-loaded maltodextrin nanoparticles as a promising treatment of toxoplasmosis on murine model

Despite being the initial choice for treating toxoplasmosis, sulfadiazine and pyrimethamine have limited effectiveness in eliminating the infection and were linked to a variety of adverse effects. Therefore, the search for new effective therapeutic strategies against toxoplasmosis is still required. The current work is the first research to assess the efficacy of spiramycin-loaded maltodextrin nanoparticles (SPM-loaded MNPs) as a novel alternative drug therapy against toxoplasmosis in a murine model. Fifty laboratory-bred Swiss albino mice were divided into five groups: normal control group (GI, n = 10), positive control group (GII, n = 10), orally treated with spiramycin (SPM) alone (GIII, n = 10), intranasal treated with SPM-loaded MNPs (GIV, n = 10), and orally treated with SPM-loaded MNPs (GV, n = 10). Cysts of Toxoplasma gondii ME-49 strain were used to infect the mice. Tested drugs were administered 2 months after the infection. Drug efficacy was assessed by counting brain cysts, histopathological examination, and measures of serum CD19 by flow cytometer. The orally treated group with SPM-loaded MNPs (GV) showed a marked reduction of brain cyst count (88.7%), histopathological improvement changes, and an increasing mean level of CD19 (80.2%) with significant differences. SPM-loaded MNPs showed potent therapeutic effects against chronic toxoplasmosis. Further research should be conducted to assess it in the treatment of human toxoplasmosis, especially during pregnancy.Graphical

The Toxoplasma oxygen-sensing protein, TgPhyA, is required for resistance to interferon gamma-mediated nutritional immunity in mice.

As Toxoplasma gondii disseminates through its host, the parasite must sense and adapt to its environment and scavenge nutrients. Oxygen (O2) is one such environmental factor and cytoplasmic prolyl 4-hydroxylases (PHDs) are evolutionarily conserved O2 cellular sensing proteins that regulate responses to changes in O2 availability. Toxoplasma expresses 2 PHDs. One of them, TgPHYa hydroxylates SKP1, a subunit of the SCF-E3 ubiquitin ligase complex. In vitro, TgPHYa is important for growth at low O2 levels. However, studies have yet to examine the role that TgPHYa or any other pathogen-encoded PHD plays in virulence and disease. Using a type II ME49 Toxoplasma TgPHYa knockout, we report that TgPHYa is important for Toxoplasma virulence and brain cyst formation in mice. We further find that while TgPHYa mutant parasites can establish an infection in the gut, they are unable to efficiently disseminate to peripheral tissues because the mutant parasites are unable to survive within recruited immune cells. Since this phenotype was abrogated in IFNγ knockout mice, we studied how TgPHYa mediates survival in IFNγ-treated cells. We find that TgPHYa is not required for release of parasite-encoded effectors into host cells that neutralize anti-parasitic processes induced by IFNγ. In contrast, we find that TgPHYa is required for the parasite to scavenge tryptophan, which is an amino acid whose levels are decreased after IFNγ up-regulates the tryptophan-catabolizing enzyme, indoleamine dioxygenase (IDO). We further find, relative to wild-type mice, that IDO knockout mice display increased morbidity when infected with TgPHYa knockout parasites. Together, these data identify the first parasite mechanism for evading IFNγ-induced nutritional immunity and highlight a novel role that oxygen-sensing proteins play in pathogen growth and virulence.

The opposing effect of acute and chronic Toxoplasma gondii infection on tumor development

BackgroundThe interplay between Toxoplasma gondii infection and tumor development is intriguing and not yet fully understood. Some studies showed that T. gondii reversed tumor immune suppression, while some reported the opposite, stating that T. gondii infection promoted tumor growth.MethodsWe created three mouse models to investigate the interplay between T. gondii and tumor. Model I aimed to study the effect of tumor growth on T. gondii infection by measuring cyst number and size. Models II and III were used to investigate the effect of different stages of T. gondii infection on tumor development via flow cytometry and bioluminescent imaging. Mouse strains (Kunming, BALB/c, and C57BL/6J) with varying susceptibilities to tumors were used in the study.ResultsThe size and number of brain cysts in the tumor-infected group were significantly higher, indicating that tumor presence promotes T. gondii growth in the brain. Acute T. gondii infection, before or after tumor cell introduction, decreased tumor growth manifested by reduced bioluminescent signal and tumor size and weight. In the tumor microenvironment, CD4+ and CD8+ T cell number, including their subpopulations (cytotoxic CD8+ T cells and Th1 cells) had a time-dependent increase in the group with acute T. gondii infection compared with the group without infection. However, in the peripheral blood, the increase of T cells, including cytotoxic CD8+ T cells and Th1 cells, persisted 25 days after Lewis lung carcinoma (LLC) cell injection in the group with acute T. gondii. Chronic T. gondii infection enhanced tumor growth as reflected by increase in tumor size and weight. The LLC group with chronic T. gondii infection exhibited decreased percentages of cytotoxic CD8+ T cells and Th1 cells 25 days post-LLC injection as compared with the LLC group without T. gondii infection. At week 4 post-LLC injection, chronic T. gondii infection increased tumor formation rate [odds ratio (OR) 1.71] in both KM and BALB/c mice.ConclusionsOur research elucidates the dynamics between T. gondii infection and tumorigenesis. Tumor-induced immune suppression promoted T. gondii replication in the brain. Acute and chronic T. gondii infection had opposing effects on tumor development.Graphical

Antiparasitic and apoptotic modulatory activities of curcumin and extracts of Nigella sativa L, Zingiber officinale Rosc., and Punica granatum L. in combination with spiramycin against chronic cerebral toxoplasmosis in immunocompromised mice

ObjectiveTo examine the effect of coadministration of different medicinal plant extracts (curcumin and extracts of Nigella sativa L. [N. sativa, Jia Hei Zhong Cao], Zingiber officinale Rosc. [Z. officinale, Sheng Jiang], and Punica granatum L. [P. granatum, Shi Liu]) with spiramycin (SP) against the cystogenic ME-49 Toxoplasma gondii (T. gondii) strain in immunocompromised mice. MethodsWe utilized 68 mice categorized into 8 groups: 2 non-infected controls (immunocompetent and immunocompromised), 1 infected control, and 5 infected and treated groups. Following the experiment, the cerebral tissues of each mouse underwent parasitological, histopathological, and immunohistochemical evaluations. ResultsCompared with the infected non-treated group, all infected treated groups showed significant reductions in brain cyst numbers (all P < .05), with the highest reduction rate (77.4%) recorded for P. granatum and SP combination (G8). Only G8 showed a significant reduction in mouse deaths compared with the other groups. With regards to restoring histopathological changes and decreasing inflammation, the groups infected and treated with curcumin and P. granatum combined with SP showed the best results (P < .05). Combinations of curcumin and extracts of Z. officinale and P. granatum with SP significantly restored the cerebral expression of caspase-3 compared with the N. sativa extract combination (P < .05). G8 showed non-significant expression compared with the local expression in the negative control groups. ConclusionOur study revealed that the coadministration of P. granatum extract with SP was the most effective combination against chronic cerebral toxoplasmosis.

Trx4, a novel thioredoxin protein, is important for Toxoplasma gondii fitness

BackgroundTo successfully replicate within the host cell, Toxoplasma gondii employs several mechanisms to overcome the host cell defenses and mitigate the harmful effects of the free radicals resulting from its own metabolic processes using effectors such as thioredoxin proteins. In this study, we characterize the location and functions of a newly identified thioredoxin in T. gondii, which was named Trx4.MethodsWe characterized the functional role of Trx4 in T. gondii Type I RH and Type II Pru strains by gene knockout and studied its subcellular localization by endogenous protein HA tagging using CRISPR-Cas9 gene editing. The enzyme-catalyzed proximity labeling technique, the TurboID system, was employed to identify the proteins in proximity to Trx4.ResultsTrx4 was identified as a dense granule protein of T. gondii predominantly expressed in the parasitophorous vacuole (PV) and was partially co-localized with GRA1 and GRA5. Functional analysis showed that deletion of trx4 markedly influenced the parasite lytic cycle, resulting in impaired host cell invasion capacity in both RH and Pru strains. Mutation of Trx domains in Trx4 in RH strain revealed that two Trx domains were important for the parasite invasion. By utilizing the TurboID system to biotinylate proteins in proximity to Trx4, we identified a substantial number of proteins, some of which are novel, and others are previously characterized, predominantly distributed in the dense granules. In addition, we uncovered three novel proteins co-localized with Trx4. Intriguingly, deletion of trx4 did not affect the localization of these three proteins. Finally, a virulence assay demonstrated that knockout of trx4 resulted in a significant attenuation of virulence and a significant reduction in brain cyst loads in mice.ConclusionsTrx4 plays an important role in T. gondii invasion and virulence in Type I RH strain and Type II Pru strain. Combining the TurboID system with CRISPR-Cas9 technique revealed many PV-localized proximity proteins associated with Trx4. These findings suggest a versatile role of Trx4 in mediating the processes that occur in this distinctive intracellular membrane-bound vacuolar compartment.Graphical

Concordance between two monoclonal antibody-based antigen detection enzyme-linked immunosorbent assays for measuring cysticercal antigen levels in sera from pigs experimentally infected with Taenia solium and Taenia hydatigena

BackgroundAntigen detection in Taenia solium cysticercosis confirms viable infection in the intermediate host (either pig or human). The reference B158/B60 monoclonal antibody (mAb)-based Ag-enzyme-linked immunosorbent assay (ELISA) has acceptable levels of sensitivity and specificity in human neurocysticercosis with multiple brain cysts, although its sensitivity is lower in cases with single brain cysts, whereas in porcine cysticercosis the assay specificity is affected by its frequent cross-reaction with Taenia hydatigena, another common cestode found in pigs. Our group has produced 21 anti-T. solium mAbs reacting against antigens of the whole cyst, vesicular fluid, and secretory/excretory products, identifying TsW8/TsW5 as the most promising pair of mAbs for an Ag-ELISA.MethodsWe report the use of the TsW8/TsW5 Ag-ELISA to measure cysticercus antigen levels [expressed as optical density (OD) values] in two panels of sera collected from day 0 (baseline) to day 90 postinfection (PI) from pigs experimentally infected with T. solium (n = 26) and T. hydatigena (n = 12). At baseline and on days 28 and 90 PI, we used Bland–Altman (BA) analysis and Lin’s concordance correlation coefficients (CCC) to determine the concordance between the TsW8/TsW5 and the B158/B60 Ag-ELISA.ResultsThe TsW8/TsW5 Ag-ELISA was able to efficiently measure circulating antigen levels in T. solium-infected pigs, similar to that obtained with the B158/B60 Ag-ELISA. Almost all paired log-OD differences between assays were within the limits of agreement (LoA) in the BA analysis at baseline and on days 28 and 90 PI (92.3%, 100%, and 100%, respectively), and a high concordance of log-ODs between assays was also found (Lin’s CCC: 0.69, 0.92, and 0.96, respectively, all P < 0.001). In pigs infected with T. hydatigena, almost all paired log-OD differences were within the LoA in the BA analysis, whereas the concordance of log-ODs between assays was low at baseline (Lin’s CCC: 0.24) but increased on days 28 and 90 PI (Lins’ CCC: 0.88 and 0.98, P < 0.001).Conclusions/significanceThe TsW8/TsW5 Ag-ELISA recognizes antigens in pigs with T. solium cysticercosis and is highly concordant with the B158/B60 Ag-ELISA. However, its diagnostic use is hampered by cross-reactions with T. hydatigena, as in other mAb-based Ag-ELISAs.Graphical

Variable arachnoid cyst presentations in variable age groups; a comparative single center study

Introduction. Arachnoid cysts are an intracranial spaces that are filled with cerebrospinal fluid (CSF) and lined with arachnoid membranes. They may be asymptomatic or present with focal epilepsy, headache and other neurological symptoms. Purpose. This study shows the different presentation of brain arachnoid cysts in relation to their locations in variable age groups. Methods. This is a retrospective analytic cohort comparative study that enrolled 168 patients was done in the Middle Euphrates Neuroscience Center and Al-Sadder Medical City, from the first of February 2020 to the first of February 2023. The collected data of patients include patient’s age, gender, presentation, location of the cyst in the brain and its dimension. Each patient was assessed a full general and neurological examination. The data were analyzed according to presentation and location of cyst in the brain via MRI. Results. The mean age of group one is 10 years (4-18 years) and for group two is 35 years (19-70 years). Regarding the gender, the male gender was more in group one, while the female gender was more in group two than in group one. Regarding the presentation, the most common presentation is focal epilepsy in about 47.61% in both groups and more in group one (about 68.11%). Regarding the MRI location of arachnoid cyst, the most common site was the temporal lobe. The overall percentage of arachnoid cyst is 57.14% in temporal lobe and 13.09% in occipital lobe in total patients Conclusion. The arachnoid cysts of brain are variable in both their presentations and their locations in different ages. The most common presentation is focal epilepsy in patient 18 years old and less, while the headache in patient older than 18 years. The most common site of cyst is temporal lobe.

Structural Characterization of Toxoplasma gondii Brain Cysts in a Model of Reactivated Toxoplasmosis Using Computational Image Analysis

Toxoplasma gondii is an obligate intracellular parasite existing in three infectious life stages—tachyzoites, bradyzoites, and sporozoites. Rupture of tissue cysts and re-conversion of bradyzoites to tachyzoites leads to reactivated toxoplasmosis (RT) in an immunocompromised host. The aim of this study was to apply ImageJ software for analysis of T. gondii brain cysts obtained from a newly established in vivo model of RT. Mice chronically infected with T. gondii (BGD1 and BGD26 strains) were treated with cyclophosphamide and hydrocortisone (experimental group—EG) or left untreated as infection controls (ICs). RT in mice was confirmed by qPCR (PCR+); mice remaining chronically infected were PCR−. A total of 90 images of cysts were analyzed for fractal dimension (FD), lacunarity (L), diameter (D), circularity (C), and packing density (PD). Circularity was significantly higher in PCR+ compared to IC mice (p &lt; 0.05 for BGD1, p &lt; 0.001 for the BGD26 strain). A significant negative correlation between D and PD was observed only in IC for the BGD1 strain (ρ = −0.384, p = 0.048), while fractal parameters were stable. Significantly higher D, C, and PD and lower lacunarity, L, were noticed in the BGD1 compared to the more aggressive BGD26 strain. In conclusion, these results demonstrate the complexity of structural alterations of T. gondii cysts in an immunocompromised host and emphasize the application potential of ImageJ in the experimental models of toxoplasmosis.

Comparison of the immune response and protection against the experimental Toxoplasma gondii infection elicited by immunization with the recombinant proteins BAG1, ROP8, and BAG1-ROP8.

Toxoplasmosis is one of the most dangerous zoonotic diseases, causing serious economic losses worldwide due to abortion and reproductive problems. Vaccination is the best way to prevent disease; thus, it is imperative to develop a candidate vaccine for toxoplasmosis. BAG1 and ROP8 have the potential to become vaccine candidates. In this study, rTgBAG1, rTgROP8, and rTgBAG1-rTgROP8 were used to evaluate the immune effect of vaccines in each group by detecting the humoral and cellular immune response levels of BABL/c mice after immunization and the ability to resist acute and chronic infection with Toxoplasma gondii (T. gondii). We divided the mice into vaccine groups with different proteins, and the mice were immunized on days 0, 14, and 28. The protective effects of different proteins against T. gondii were analysed by measuring the cytokines, serum antibodies, splenocyte proliferation assay results, survival time, and number and diameter of brain cysts of mice after infection. The vaccine groups exhibited substantially higher IgG, IgG1, and IgG2a levels and effectively stimulated lymphocyte proliferation. The levels of IFN-γ and IL-2 in the vaccine group were significantly increased. The survival time of the mice in each vaccine group was prolonged and the diameter of the cysts in the vaccine group was smaller; rTgBAG1-rTgROP8 had a better protection. Our study showed that the rTgBAG1, rTgROP8, and rTgBAG1-rTgROP8 recombinant protein vaccines are partial but effective approaches against acute or chronic T. gondii infection. They are potential candidates for a toxoplasmosis vaccine.

Intracranial Arachnoid Cyst in Children: Clinical Presentation and Risk Factors for Surgical Intervention

Plain Language SummaryPediatric imaging findings of brain cysts are a common finding. Some cysts do not require surgical intervention while others may require surgery. We conducted a retrospective chart review from 2009 to 2021 on patients aged 0–21 years of age who were found to have a brain cyst on imaging reports. Our aim was to identify clinical risk factors in patients with brain cysts who underwent surgery versus those who did not. A total of 230 patients were included in the study, of which 45 (19.6%) underwent surgery. Overall, surgical patients were younger (median age 1.1 years) and had a median cyst volume larger (41.7 cm3), compared to nonsurgical patients (median age 5.9 years, volume 11.8 cm3, respectively). The most common reason to undergo initial imaging was headache for nonsurgical patients (54/185, 29.2%) while surgical patients had initial imaging due to large head size (11/45, 24.4%) or imaging carried out prenatally to 1 year of life (11/45, 24.4%). We found that cyst volume and age at diagnosis were predictors for surgical intervention. The greater the cyst volume was at initial diagnosis and the younger the patient was at time of diagnosis, the greater the odds the patient had of undergoing surgical intervention. Therefore these patients should be monitored closely for development of symptoms indicating a need for surgical intervention.

Zinc Oxide and Magnesium-Doped Zinc Oxide Nanoparticles Ameliorate Murine Chronic Toxoplasmosis.

Toxoplasma gondii causes a global parasitic disease. Therapeutic options for eradicating toxoplasmosis are limited. In this study, ZnO and Mg-doped ZnO NPs were prepared, and their structural and morphological chrematistics were investigated. The XRD pattern revealed that Mg-doped ZnO NPs have weak crystallinity and a small crystallite size. FTIR and XPS analyses confirmed the integration of Mg ions into the ZnO framework, producing the high-purity Mg-doped ZnO nanocomposite. TEM micrographs determined the particle size of un-doped ZnO in the range of 29 nm, reduced to 23 nm with Mg2+ replacements. ZnO and Mg-doped ZnO NPs significantly decreased the number of brain cysts (p < 0.05) by 29.30% and 35.08%, respectively, compared to the infected untreated group. The administration of ZnO and Mg-doped ZnO NPs revealed a marked histopathological improvement in the brain, liver, and spleen. Furthermore, ZnO and Mg-doped ZnO NPs reduced P53 expression in the cerebral tissue while inducing CD31 expression, which indicated a protective effect against the infection-induced apoptosis and the restoration of balance between free radicals and antioxidant defense activity. In conclusion, the study proved these nanoparticles have antiparasitic, antiapoptotic, and angiogenetic effects. Being nontoxic compounds, these nanoparticles could be promising adjuvants in treating chronic toxoplasmosis.

Investigation of the effects of Toxoplasma gondii on behavioral and molecular mechanism in bradyzoite stage

Toxoplasma gondii is a single-celled parasite that causes a disease called toxoplasmosis. It can reach the central nervous system, but the mechanism of T. gondii disrupting the functioning of these brain regions occurs in bradyzoite stage of parasite, causing brain damage by forming tissue cysts in brain. In our study, the effects of T. gondii on locomotor activity, anxiety, learning and memory, and norepinephrine (NE), levodopa (L-DOPA), dopamine (DA) and 3,4-D-dihydroxyphenylacetic acid (DOPAC) catecholamines in amygdala, striatum, prefrontal cortex and hippocampus regions of the brain were investigated in bradyzoite stage. Twenty male Albino mice Mus musculus, 4–5 weeks old, weighing 20–25 g, were used. T. gondii inoculated to mice intraperitonealy with 48–50-hour passages of T. gondii RH Ankara strain. For intraperitoneal inoculation of mice 5x104 tachyzoites per mouse. No inoculation was made in control group (n: 20). Locomotor activity behavior in open field test (OFT), anxious behavior in elevated plus maze (EPM), and learning behavior in novel object recognition (NOR) tests were evaluated. NE, L-DOPA, DA and DOPAC were measured by HPLC in brain tissues of amygdala, striatum, prefrontal cortex and hippocampus. A decrease was observed in the locomotor activity, anxiety and learning values of the T. gondii group compared to the control group (p < 0.05). The heighten in NE and L-DOPA levels in amygdala tissue of T. gondii group compared to control group, an elevation in NE, L-DOPA, DA and DOPAC levels in striatum tissue, and an increase in levels of NE in prefrontal cortex tissue were detected in monoamine results. In hippocampus tissue, an increase was observed in DA levels, while a decrease was observed in NE, L-DOPA and DOPAC levels. In our study, it has been shown that T. gondii in bradyzoite stage reduces locomotor activity, causes learning and memory impairment, and has anxiogenic effects.

Mineralization Reduces the Toxicity and Improves Stability and Protective Immune Response Induced by Toxoplasma gondii.

Vaccination is an ideal strategy for the control and prevention of toxoplasmosis. However, the thermostability and effectiveness of vaccines limit their application. Here, calcium mineralization was used to fabricate Toxoplasma gondii tachyzoites as immunogenic core-shell particles with improved immune response and thermostability. In the current study, T. gondii RH particles coated with mineralized shells were fabricated by calcium mineralization. The mineralized shells could maintain the T. gondii tachyzoites structural integrity for at least 12 months and weaken the virulence. Immunization of mice with mineralized tachyzoites induced high levels of T. gondii-specific antibodies and cytokines. The immunized mice were protected with a 100% survival rate in acute and chronic infection, and brain cyst burdens were significantly reduced. This study reported for the first time the strategy of calcium mineralization on T. gondii and proved that mineralized tachyzoites could play an immune protective role, thus expanding the application of biomineralization in T. gondii vaccine delivery.

Mitochondrial dysfunction induced by bedaquiline as an anti-Toxoplasma alternative

Toxoplasma gondii is a zoonotic parasite that infects one-third of the world’s population and nearly all warm-blooded animals. Due to the complexity of T. gondii’s life cycle, available treatment options have limited efficacy. Thus, there is an urgent need to develop new compounds or repurpose existing drugs with potent anti-Toxoplasma activity. This study demonstrates that bedaquiline (BDQ), an FDA-approved diarylquinoline antimycobacterial drug for the treatment of tuberculosis, potently inhibits the tachyzoites of T. gondii. At a safe concentration, BDQ displayed a dose-dependent inhibition on T. gondii growth with a half-maximal effective concentration (EC50) of 4.95 μM. Treatment with BDQ significantly suppressed the proliferation of T. gondii tachyzoites in the host cell, while the invasion ability of the parasite was not affected. BDQ incubation shrunk the mitochondrial structure and decreased the mitochondrial membrane potential and ATP level of T. gondii parasites. In addition, BDQ induced elevated ROS and led to autophagy in the parasite. By transcriptomic analysis, we found that oxidative phosphorylation pathway genes were significantly disturbed by BDQ-treated parasites. More importantly, BDQ significantly reduces brain cysts for the chronically infected mice. These results suggest that BDQ has potent anti-T. gondii activity and may impair its mitochondrial function by affecting proton transport. This study provides bedaquiline as a potential alternative drug for the treatment of toxoplasmosis, and our findings may facilitate the development of new effective drugs for the treatment of toxoplasmosis.