Centella asiatica extract ameliorates deoxygenation-induced neurological dysfunction in zebrafish larvae.

Background: Oxygen deprivation (OD) is a critical condition that can lead to brain damage and even death. Current hypoxia management approaches are limited in effectiveness. Centella asiatica (CA), known for its neuroprotective properties, offers a potential alternative for OD treatment. Aims: This study aims to investigate the neuroprotective effects of CA on the expression of brain-derived neurotrophic factor (BDNF) and vesicular glutamate transporter 1 (VGLUT1) in zebrafish larvae under oxygen-deficient conditions. Methods: Zebrafish embryos were subjected to low oxygen levels (1.5 mg/l) 0-2 hours post-fertilization (hpf) until 3 days post-fertilization (dpf), simulating the early stages of OD. Subsequent treatment involved varying concentrations of CA (1.25-5 µg/ml) up to 9 days post-fertilization. The expression levels of BDNF and VGLUT1 were measured using PCR methods. Statistical analysis was conducted using a two-way analysis of variance to evaluate the impact of CA on the expression of BDNF and VGLUT1 in zebrafish larvae aged 3 and 9 dpf in oxygen-deprived conditions. Results: CA significantly influenced the expression of BDNF and VGLUT1 under OD (p < 0.001). An increase in BDNF expression (p < 0.001) and a decrease in VGLUT1 (p < 0.01) were observed in zebrafish larvae experiencing OD and treated with CA. There was no significant difference in BDNF and VGLUT1 expression across age variations in zebrafish larvae at 3 dpf and 9 dpf in the treatment groups (p > 0.05). CA concentration of 2.5 µg/ml effectively enhanced BDNF and reduced VGLUT1 in 3-9 dpf zebrafish larvae. Conclusion: CA demonstrates potential as a neuroprotective agent, modulating increased BDNF expression and reduced VGLUT1 under OD conditions. These findings lay a foundation for further research in developing therapies for oxygen deficiency.

Asiatic acid increased locomotor and head width by inducing brain-derived neurotrophic factor in intrauterine hypoxia-exposed zebrafish.

Background: Hypoxia ischemia leads to abnormal behavior and growth. Prenatal hypoxia also decreases brain adaptive potential, which can cause fatal effects such as cell death. Asiatic acid (AA) in Centella asiatica is a neuroprotector through antioxidant and anti-inflammatory activities. Aim: This study aimed to analyze the effect of AA as a neuroprotector against hypoxia during intrauterine development on locomotor activity, head width, and brain-derived neurotrophic factor (BDNF) expression. Methods: The true experimental laboratory research used a posttest control-only design. Zebrafish embryos (Danio rerio) aged 0-2 dpf (days postfertilization) were exposed to hypoxia with oxygen levels reaching 1.5 mg/l. Then, AA was administered at successive concentrations, namely, 0.36, 0.72, and 1.45 µg/ml, at 2 hpf (hours postfertilization), 3, 6, and 9 dpf. Head width, velocity activity, and BDNF expression were observed. Results: Intrauterine hypoxia significantly decreased head width, velocity rate, and BDNF expression (<0.001). Administration of AA at all concentrations and age 9 dpf to zebrafish larvae with intrauterine hypoxia exposure increased head width ( p < 0.0001), velocity (p < 0.05), and relative mRNA expression of BDNF (p < 0.05). Conclusion: AA is potentially neuroprotective to the brain in zebrafish larvae exposed to hypoxia during intrauterine development.

Asiatic acid in Centella asiatica extract towards morphological development in an intermittent hypoxia intrauterine embryo model and molecular prediction pathway of insulin-like growth factor-1 receptor signalling.

Background: Hypoxia during pregnancy generates oxidative stress that alters the growth and development of the human fetus. Insulin-like growth factor-1 (IGF-1) receptors are essential for normal fetal growth. Asiatic acid in Centella asiatica (CA) has antioxidant properties to prevent growth impairment in hypoxia. Aims: This study aimed to investigate the effect of asiatic acid on the morphological development of an intermittent hypoxia (IH) zebrafish embryo model and analyze molecular docking prediction in IGF-1 receptor (IGF-1R) signaling. Methods: Embryos of zebrafish at 2 hours postfertilization (hpf) were assigned to control negative (C), IH, and combination IH and CA extract groups consisting of 1.25 (IHCA1), 2.5 (IHCA2), and 5 (IHCA3) µg/ml. Hypoxia treatment (conducted 4 hours/day) and CA extract were administered for 3 days (2-72 hpf). The parameters of body length and head length were evaluated at 3, 6, and 9 days postfertilization (dpf). The data were analyzed by a two-way analysis of variance (p < 0.05). Molecular docking was performed to explore the binding affinity of asiatic acid to IGF-1R by Molegro Virtual Docker ver.5 software. Results: The body length and head length of embryos in the IH and treatment groups (IHCA) were shorter than those in the control group at 3 dpf (p < 0.05). However, the body length was more prolonged in the IHCA1 group, but the head length was longer in the IHCA2 group than in the IH group at 6 and 9 dpf. Molecular docking showed the reliable interaction of asiatic acid with IGF-1R signaling in an IH animal model. Conclusion: The administration of CA extract benefits IH through the development and growth of zebrafish embryos at a dose of 2.5-5 µg/ml. Asiatic acid has a binding affinity for IGF-1R signaling.

Predictors of neurocognitive and psychological disorders in children after intensive care admission: A prospective cohort study.

Background and Aims: Children admitted in the pediatric intensive care unit (PICU) often deal with long-term morbidities affecting physical, cognitive, emotional, social, and psychiatric symptoms. We aimed to identify the internal and external factors which predict the occurrence of neurocognitive and psychological disorders in survivors at 3 months after PICU discharge. Methods: We identified 53 critically ill children, ages 4-18 years old, admitted in PICU for more than 24 h, and survived. We evaluated neurocognitive disorder with Pediatric Cerebral Perfomance Category (PCPC) and psychological disorders with Strengths and Difficulties Questionnaire (SDQ) at the time of PICU discharge and repeated in 3 months afterward. We evaluated the internal and external risk factors related to neurocognitive and psychological disorders in PICU survivors. The internal risk factors were age, gender, family composition, and socioeconomic status. The external risk factors were: surgical intervention, neurological disease, predicted death rate by pediatric index mortality (PIM)-2 score, PICU length of stay (LOS), days of mechanical ventilation, and the number of therapeutic interventions. Results: There were significant improvement in neurocognitive disorders (p < 0.001), peer problems, (p = 0.01), and prosocial behaviors (p = 0.00) in children at 3 months after the PICU discharge. Age of 4-5 years has a significant effect on neurocognitive disorders (p = 0.04), while male gender (p = 0.02), low-social economy, non-intact family composition (p = 0.01), neurological disease (p = 0.04), surgical intervention (p = 0.01), and TISS score (p = 0.00) have a significant effect on psychological disorders in children at 3 months after the PICU discharge. Conclusion: Neurocognitive disorders, peer problems, and prosocial behaviors improved in a few patients 3 months after PICU discharge. Age of 4-5 years was a risk factor of the persisted neurocognitive disorder, whereas male gender, low-social economy, non-intact family composition, neurological disease, surgical intervention, and TISS score were risk factors of persisted psychological disorder at 3 months after PICU.

Postpartum hemorrhage in maternal mothers at Anutapura Public Hospital in Palu, 2017

Objective: Postpartum hemorrhage is one of the factors causing maternal mortality in Indonesia. In Indonesia, at least 128.000 women suffer from hemorrhage, causing them to death. Data from the Anutapura Public Hospital in Palu showed that the rate of postpartum hemorrhage within 2015–2017 was fluctuated and still caused maternal mortality. This study aimed to determine the risk factors of the incidence of postpartum hemorrhage in maternal mothers at Anutapura Public Hospital, Palu. Method: The type of study was observational with a case-control approach. The subject of the study was mothers having a postpartum hemorrhage. The total sample of this study was 50 people as the case group and 100 people as the control group by adjusting the types of labor. Sampling was done using a total sampling technique. The data were analyzed using an odds ratio test with α = 5%. Result: This study showed that anemia (OR = 2.874 and CI = 1.421–5.812), parity (OR = 3.995 and CI = 1.952–8.174), age (OR = 2.874 and CI = 1.421–5.812) were the risk factors of postpartum hemorrhage in women. Conclusion: The anemia, parity, and age are the risk factors of postpartum hemorrhage in women. The importance of increasing ANC (antenatal care) visits is to control maternal and fetal health and provide information through a medical consultation about the importance of planning a good pregnancy. (AU)