| DB ID | MyCo_2699 |
| Title | Neuroinflammation and structural injury of the fetal ovine brain following intra-amniotic Candida albicans exposure |
| Year | 2016 |
| PMID | 26842664 |
| Fungal Diseases involved | Intra-amniotic Candida albicans Fungal infection |
| Associated Medical Condition | Chorioamnionitis |
| Genus | Candida |
| Species | albicans |
| Organism | Candida albicans |
| Ethical Statement | The study was approved by and performed according to the guidelines of the animal ethics committee of the University of Western Australia (Perth, Australia). |
| Site of Infection | Brain |
| Opportunistic invasive | None |
| Sample type | Biopsy |
| Sample source | Tissue Supernatant |
| Host Group | Animal |
| Host Common name | Sheep |
| Host Scientific name | Merino ewes |
| Biomarker Name | CAS3 |
| Biomarker Full Name | Caspase-3 |
| Biomarker Type | Diagnostic |
| Biomolecule | Protein |
| Geographical Location | Australia |
| Cohort | Twenty-six date-mated Merino ewes with singleton pregnancies were randomly assigned to receive an intra-amniotic injection of saline (2 mL) as a control or C. albicans (107 colony-forming units [CFU], Western Australian clinical isolate). After 2 days, an intra-amniotic/-peritoneal injection of fluconazole (30 mg per injection, Claris Life Sciences Limited, Chacharwadi-vasana, Ahmedabad- 382 213, India) or saline (controls) was administered with delivery after 1 and 3 days. Intra-amniotic injections were performed as previously described. We did not include a 5-day C. albicans-only group since previous results with this model indicated that 5 days exposure to C. albicans alone was lethal. Given the survival of the 5-day C. albicans-/fluconazoletreated group, we have concluded that fluconazole in this model increases survival. |
| Cohort No. | 26 |
| Age Group | None |
| P Value | p<0.05 |
| Sensitivity | None |
| Specificity | None |
| Positive Predictive Value | None |
| MIC | None |
| Fold Change | None |
| Pathway | None |
| Disease Introduction Mechanism | Preterm birth is associated with chorioamnionitis which is defined as inflammation of the fetal membranes and amniotic fluid caused by microbial invasion. The microorganisms most frequently associated with this condition include Ureaplasma species, Mycoplasma hominis, and Gardnerella vaginalis, all of which most commonly originate from the lower reproductive tract. These microorganisms and/or inflammatory mediators in the amniotic cavity can cause a fetal inflammatory response syndrome (FIRS). Chorioamnionitis and subsequent FIRS are independent risk factors for adverse outcomes, including injury of the fetal brain. Adverse neurodevelopmental outcomes result from diffuse cerebral inflammation and white matter injury, periventricular leukomalacia, and intraventricular hemorrhage. These conditions are associated with a high mortality rate, and survivors are predisposed to longterm morbidity including mental retardation, impaired learning, visual disorders, and in severe cases, cerebral palsy. The pathophysiology of chorioamnionitis can also include viral and fungal species. Candida albicans (C. albicans) is a commensal fungus of the gastro-intestinal tract which can be asymptomatic in the vaginal microbiota with increasing incidence during pregnancy. Intraamniotic C. albicans infections are associated with high mortality rates and severely impaired neurodevelopmental outcomes in which the mechanisms linking fetal exposure to neurological pathologies remain essentially unstudied. We hypothesized that antenatal exposure to C. albicans caused a neuroinflammatory response and subsequent white matter injury, which we tested by exposing fetal sheep to intra-amniotic C. albicans. |
| Technique | ELISA |
| Analysis Method | ELISA Based |
| ELISA kits | None |
| Assay Data | None |
| Validation Techniques used | ELISA, Immunohistochemistry, Immunofluorescence |
| Up Regulation Down Regulation | Increase |
| Sequence Data | None |
| External Link | None |