Epilepsy Research Now in 3D: Harnessing the Power of Brain Organoids in Epilepsy

Brain organoids represent a powerful tool for studying human neurological diseases, particularly those that affect brain growth and structure. However, many diseases manifest with clear evidence of physiological and network abnormality in the absence of anatomical changes, raising the question of whether organoids possess sufficient neural network complexity to model these conditions. Here, we explore the network-level functions of brain organoids using calcium sensor imaging and extracellular recording approaches that together reveal the existence of complex network dynamics reminiscent of intact brain preparations. We demonstrate highly abnormal and epileptiform-like activity in organoids derived from induced pluripotent stem cells from individuals with Rett syndrome, accompanied by transcriptomic differences revealed by single-cell analyses. We also rescue key physiological activities with an unconventional neuroregulatory drug, pifithrin-α. Together, these findings provide an essential foundation for the utilization of brain organoids to study intact and disordered human brain network formation and illustrate their utility in therapeutic discovery.

Assessment of Stunting Status and Stunting Prevention Efforts in Toddlers in Penajam District, North Penajam Paser Regency

North Penajam Paser Regency (PPU) is one of the 100 priority districts/cities for stunting intervention in Indonesia. The prevalence of stunting in PPU Regency is 27%, while the prevalence in East Kalimantan is 28.3%, and nationally, 36.4%. Stunting has an impact on impaired brain growth, physical growth, and development. The purpose of community service is to analyze the characteristics of stunting toddlers and stunting prevention through posyandu activities. The method of implementing descriptive-analytic through secondary data collection activities for stunted toddlers is described. Posyandu activities for toddlers through health checks, providing nutrition education to toddlers in the villages of Penajam, Gunung Steleng, Nipah Nipah, and Nenang. Literature study on the prevention of stunting under five by the local government of PPU Regency. The results showed that there were 92 stunting toddlers, 53 boys, and 39 girls, with 68 short toddlers and 24 very short toddlers, most of whom were >24 -60 months old, i.e. 59 toddlers. Stunting prevention includes health checks for children under five, education on stunting prevention at posyandu and strengthening of stunting prevention/control policies with Regent Regulations. More optimal efforts are needed in implementing the Regent's regulation for the prevention of stunting under five.

The Role of Adequate Nutrition on Early Stages of Child Development. New Aspects of Goat Milk-Based Infant Formulas Implementation

The early stages of child development are characterized by various processes of maturation such as brain growth and development. The digestive and immune systems are developing as well at the same time. The intestinal microbiota plays significant role in the development of all organs and systems. Various disorders of microbial colonization of digestive system can negatively affect food programming processes. Nutrition type (breastfeeding or artificial) also has its own noticeable effect on early development. Breastfeeding is the “gold standard” in children’s nutrition. Modern approaches on creation of adapted formulas based on goat’s milk allow to develop its optimal composition (protein fraction for easy digestion, -palmitate, oligosaccharides, and natural nucleotides) that has positive effect on the child’s development.

Time is of the essence: the molecular mechanisms of primary microcephaly

Primary microcephaly is a brain growth disorder characterized by a severe reduction of brain size and thinning of the cerebral cortex. Many primary microcephaly mutations occur in genes that encode centrosome proteins, highlighting an important role for centrosomes in cortical development. Centrosomes are microtubule organizing centers that participate in several processes, including controlling polarity, catalyzing spindle assembly in mitosis, and building primary cilia. Understanding which of these processes are altered and how these disruptions contribute to microcephaly pathogenesis is a central unresolved question. In this review, we revisit the different models that have been proposed to explain how centrosome dysfunction impairs cortical development. We review the evidence supporting a unified model in which centrosome defects reduce cell proliferation in the developing cortex by prolonging mitosis and activating a mitotic surveillance pathway. Finally, we also extend our discussion to centrosome-independent microcephaly mutations, such as those involved in DNA replication and repair.

Association between Fat-Free Mass and Brain Size in Extremely Preterm Infants

Postnatal growth restriction and deficits in fat-free mass are associated with impaired neurodevelopment. The optimal body composition to support normal brain growth and development remains unclear. This study investigated the association between body composition and brain size in preterm infants. We included 118 infants born <28 weeks of gestation between 2017–2021, who underwent body composition (fat-free mass (FFM) and fat mass (FM)) and cerebral magnetic resonance imaging to quantify brain size (cerebral biparietal diameter (cBPD), bone biparietal diameter (bBPD), interhemispheric distance (IHD), transverse cerebellar diameter (tCD)) at term-equivalent age. FFM Z-Score significantly correlated with higher cBPD Z-Score (rs = 0.69; p < 0.001), bBPD Z-Score (rs = 0.48; p < 0.001) and tCD Z-Score (rs = 0.30; p = 0.002); FM Z-Score significantly correlated with lower brain size (cBPD Z-Score (rs = −0.32; p < 0.001) and bBPD Z-Score (rs = −0.42; p < 0.001). In contrast weight (rs = 0.08), length (rs = −0.01) and head circumference Z-Score (rs = 0.14) did not. Linear regression model adjusted for important neonatal variables revealed that FFM Z-Score was independently and significantly associated with higher cBPD Z-Score (median 0.50, 95% CI: 0.59, 0.43; p < 0.001) and bBPD Z-Score (median 0.31, 95% CI: 0.42, 0.19; p < 0.001); FM Z-Score was independently and significantly associated with lower cBPD Z-Score (median −0.27, 95% CI: −0.42, −0.11; p < 0.001) and bBPD Z-Score (median −0.32, 95% CI: −0.45, −0.18; p < 0.001). Higher FFM Z-Score and lower FM Z-scores were significantly associated with larger brain size at term-equivalent age. These results indicate that early body composition might be a useful tool to evaluate and eventually optimize brain growth and neurodevelopment.

Brain GRowth Evaluation Assessed with Transfontanellar (B-GREAT) ultrasound. Old and new bedside markers to estimate cerebral growth in preterm infants: a pilot study

Objective: We aimed to investigate the feasibility of evaluating overall preterm brain growth using a gathered set of measurements of brain structures in standard cranial ultrasound planes. We called this method of assessment Brain GRowth Evaluation Assessed with Transfontanellar ultrasound (B-GREAT). Study design: In this prospective observational cohort study, cranial ultrasound was regularly performed (on day 1, 2, 3, 7 of life and then weekly until discharge and at term) in preterm infants born with a gestational age less than 32 weeks. We evaluated Corpus Callosum (CC) length, Corpus Callosum-Fastigium (CCF) length, Anterior Horn Width (AHW), Frontal White Matter (FWM) height, Total brain Surface (TBS), Deep Grey Matter (DGM) height, Hemisphere Height (HH), Transverse Cerebellar Diameter in the axial view (TCDax) and coronal view (TCDcor). Measurements obtained were used to develop growth charts for B-GREAT markers as a function of postmenstrual age. Reproducibility of B-GREAT markers was studied. Results: A total of 528 cranial ultrasounds was performed in 80 neonates (median birth gestational age: 28+5 weeks, interquartile range: 27+3 to 30+5). The intraclass correlation coefficients for intra-observer and inter-observer analyses showed substantial agreement for all B-GREAT markers. Growth curves for B-GREAT markers were developed. Conclusion: B-GREAT is a feasible and reproducible method for bedside monitoring of the growth of the main brain structures in preterm neonates.

Fetal brain growth and infant autistic traits

Background Research indicates that structural differences exist in the brains of individuals who later display developmental conditions (e.g., autism). To date only a handful of studies have explored the relationship between fetal brain growth and later infant outcomes, with a particular focus on fetal head circumference (HC) as a proxy for brain development. These findings have been inconsistent. We investigate whether fetal brain measurements correlate with the emergence of autistic traits in toddlers. Method 219 singleton pregnancies (104 males and 115 females) were recruited at the Rosie Hospital, Cambridge, UK. A 2D ultrasound was performed at 12-, 20- and between 26-30-weeks of pregnancy, measuring head circumference (HC), ventricular atrium (VA) and transcerebellar diameter (TCD). 178 infants were subsequently followed up at 18-20 months of age and completed the Quantitative Checklist for Autism in Toddlers (Q-CHAT) to observe early autistic traits. Results HC was larger in males than in females in both the second and third trimester. There was a significant positive association between TCD size at 20 weeks and Q-CHAT scores at 18-20 months of age, found in both univariate and multivariate analyses, and this remained significant after controlling for sex. Conclusion There is a positive relationship between cerebellar (TCD) development at 20 weeks gestation and the later emergence of autistic traits (at 18-20 months of age). Atypical neurodevelopment may start prenatally. If replicated these findings could facilities early diagnosis and improved outcomes.

Maternal One-carbon Metabolism during the Periconceptional Period and Human Foetal Brain Growth: A Systematic Review

The maternal environment during the periconceptional period influences foetal growth and development, in part, via epigenetic mechanisms moderated by one-carbon metabolic pathways. During embryonic development, one-carbon metabolism is involved in brain development and neural programming. Derangements in one-carbon metabolism increase (i) the short-term risk of embryonic neural tube-related defects and (ii) long-term childhood behaviour, cognition, and autism spectrum disorders. Here we investigate the association between maternal one-carbon metabolism and foetal and neonatal brain growth and development. Database searching resulted in 26 articles eligible for inclusion. Maternal vitamin B6, vitamin B12, homocysteine, and choline were not associated with foetal and/or neonatal head growth. First-trimester maternal plasma folate within the normal range (> 17 nmol/L) associated with increased foetal head size and head growth, and high erythrocyte folate (1538–1813 nmol/L) with increased cerebellar growth, whereas folate deficiency (< 7 nmol/L) associated with a reduced foetal brain volume. Preconceptional folic acid supplement use and specific dietary patterns (associated with increased B vitamins and low homocysteine) increased foetal head size. Although early pregnancy maternal folate appears to be the most independent predictor of foetal brain growth, there is insufficient data to confirm the link between maternal folate and offspring risks for neurodevelopmental diseases.