Group B Streptococcus (GBS) colonization lead to placental infection and inflammation, known as chorioamnionitis (CA). Fetal exposure to CA is linked to elevated risks of neurobehavioral impairments in offspring, including autism spectrum disorder, which is more prominent in males than females. In our preclinical model of GBS-induced CA, males exhibited heightened placental inflammation compared to females, correlating with more severe subsequent neurobehavioral impairments. We hypothesize that androgens upregulate the placental immune response in male fetuses, potentially contributing to GBS-induced autistic-like traits in male offspring. Our previous findings demonstrated that there were reduced pro-inflammatory cytokines and polymorphonuclear cell infiltration in flutamide (androgen receptor antagonist) plus GBS-infected compared to vehicle plus GBS-infected placenta. In this study we investigated the effect of end gestational androgen blockade on brain injury patterns and neurobehavioral outcomes in offspring in utero exposed to GBS CA.

Prenatal alcohol exposure (PAE) can lead to a wide spectrum of deficits in growth and neurological function, and there is an established link between PAE and auditory dysfunction. However, the effects of PAE on auditory development are complex and vary depending on the age and pattern of alcohol exposure. In this study, we developed a mouse model of PAE during the first half of the gestational period, mimicking alcohol consumption during the first trimester of pregnancy in humans. This exposure did not affect overall growth or induce anxiety-related symptoms in the offspring, as indicated by normal body weight change and largely unchanged behaviors in the open field and elevated zero maze tests. However, several aspects of auditory function were affected by PAE. Offspring born from prenatal alcohol-exposed dams displayed smaller auditory brainstem responses (ABRs) at 2-month-old as compared to those from control dams, suggesting weakened neuron synchronization within auditory brainstem circuits. Additionally, a reduction in the reproducibility of ABR peaks III/IV was observed in PAE offspring. In contrast, the overall hearing sensitivity and neuron transmission was not affected by PAE, as evaluated by ABR thresholds or peak latencies. In an acoustic startle test, PAE offspring failed to display prepulse inhibition to low levels of prepulses more frequently than control offspring at both 2 weeks old and 2 months old, suggesting an early-onset and lasting deficit in auditory gating or sound level differentiation. Together, these results demonstrate that mice exposed to alcohol during early gestation have largely preserved auditory responses but show significant alterations in specific features of auditory processing.

The proper functioning of the central nervous system depends on the cooperation of distinct neuronal subtypes generated during development. Here, we review new insights provided by recent research and technological advances into the mechanisms underlying the generation of the remarkable diversity of inhibitory GABAergic neurons (INs). INs are generated in the ventral telencephalon or subpallium and migrate long distances to populate multiple brain regions. INs exhibit considerable morphological, molecular and electrophysiological diversity. This diversity is mediated by intrinsic and extrinsic factors, including secreted molecules (such as Sonic Hedgehog). This review examines the role of extrinsic factors in the establishment of distinct subpallial domains and the subsequent emergence of IN diversity. We begin by summarizing the in vivo morphogenesis of this process and then highlight the new technologies that allow us to revisit the role of morphogens in subpallial development and IN specification.

Introduction Perinatal stroke causes lasting neurological deficits and there are currently no effective treatment options. Established animal models of perinatal stroke do not always mimic the clinical presentation of neonatal injury or are technically challenging to perform. The photothrombotic (PT) stroke model is a minimally invasive method that replicates focal ischemic injury. Few studies have applied the PT model in neonatal contexts, and none have examined both short- and long-term effects across varying injury severities. This study aimed to optimise a protocol to create a mild model of perinatal stroke and subsequently characterize injury progression, neuropathological impact, and motor deficits over time. Methods On post-natal day (PND) 10 we used the PT method to induce perinatal stroke in rat pups. Pups were exposed to various light exposure times (10, 20 or 30 minutes) to determine the optimal time needed to produce a mild and reproducible cortical stroke injury. Behavioural assessments were conducted on days 4, 10, 20, and 30 post-injury. Brains were collected for analysis on days 3 and 40 post-injury. Results 3 days post-injury, the 20 and 30-minute group had significant focal lesions and microbleeds were present in each of the PT groups. All PT groups showed significant neuron loss in the penumbra and the thalamus, and microglia activation in multiple brain regions. As 30 minutes of light exposure showed extensive cortical tissue loss (>70%), we excluded the 30-minute group from long-term assessment. 40 days post-injury, the 10 and 20-minute groups demonstrated significant tissue loss and neuronal loss in the penumbra and thalamus, but only the 20-minute group showed neuron loss in the hippocampus. The 10- and 20-minute groups both demonstrated ongoing motor deficits. Conclusion Our results demonstrate that increasing light exposure time in PT stroke results in a more severe stroke phenotype. 30 minutes of light exposure resulted in a severe injury at only 3 days post insult, therefore, was not further investigated. 10 and 20 minutes of light exposure had a similar effect at 3 days, however after 40 days the 20-minute exposure time created a moderate injury phenotype. From this study we propose that 10 minutes of light exposure is optimal to create a mild stroke phenotype and is associated with motor deficits and altered neuropathology. This injury phenotype provides a focal and reproducible injury, while still being mild enough to feasibly test therapeutics.

Multiple lines of evidence suggest that some cases of OCD are underlain by autoimmune and/or inflammatory processes that act on the brain to create neuropsychiatric symptomatology. However, studies of immunomodulatory treatments for such cases are sparse. Here we present consecutive cases of presumed-neuroimmune OCD in youth that have been treated with rituximab +/- adjunctive immunomodulatory treatments.

Branched chain amino acid (BCAA) metabolism plays roles in various cellular processes, including energy homeostasis, anabolic signaling, and production of glutamate, the primary excitatory neurotransmitter. Emerging evidence also suggests BCAA metabolism has relationships to inflammatory and hypoxic cellular responses. Recent work in adult and adolescent clinical populations has suggested that BCAA dietary supplementation may improve outcomes associated with traumatic brain injury (TBI). Given these links, examining the putative mechanisms and potential therapeutic applications of modulating dietary BCAA content in the context of inflammatory and hypoxic developmental brain injury may reveal mechanisms for intervention in affected infants.

It is well established that therapeutic hypothermia improves outcomes for infants with moderate-severe hypoxic-ischemic encephalopathy in high-income counties. However, ~29 % of the infants treated with therpeutic hypothermia still have adverse outcome. Additionally, therapeutic hypothermia is not recommended as a treatment for infants with HIE in low- and middle-income countries. Therefore, there is an urgent need to develop alternative treatments for infants with HIE in middle- and low-income countries, as well as additive treatments to therapeutic hypothermia in high-income countries. Caffeine is widely used as an agent to prevent apnea in preterm infants, and more recently, it has been investigated as a potential neuroprotective treatment for perinatal hypoxic-ischemic brain injury, but the preclinical evidence so far has been mixed. Furthermore, there are concerns that caffeine, which is an adenosine receptor antagonist, could abolish the endogenous neuroprotective effects of adenosine, during and after hypoxia-ischemia. Further studies, particularly in large animal translational models of hypoxic-ischemic brain injury are required to establish the safety and efficacy of caffeine in this setting before conducting large randomized controlled trials.

GAPDH, β-actin, and β-tubulin are essential housekeeping proteins commonly used as reference controls for protein expression studies. GAPDH is a key glycolytic enzyme that facilitates the production of cellular energy, while β-actin and β-tubulin are major structural components of the cytoskeleton. Besides their well-established housekeeping functions, emerging studies have demonstrated critical roles for these proteins in brain developmental and pathological processes. However, few studies have examined how the expression patterns of these proteins change throughout mammalian brain development to adulthood. Considering the dynamic structural and functional changes that occur during brain development and the roles of GAPDH, β-actin, and β-tubulin in related biological processes, we investigated the developmental expression levels of these proteins in the mouse cortex at various embryonic (E15-P0) and postnatal (P0-P20, adult) stages using western blotting analysis with total protein normalization. We identified a substantial increase in GAPDH protein levels and a decrease in β-actin and β-tubulin in protein levels in the mouse cortex between birth and early adulthood, which occurred during the second week of postnatal life. Analysis of RNA-seq data from the ENCODE Consortium revealed correlated changes at the RNA transcript level. Overall, our study reveals robust age-dependent changes in cortical GAPDH, β-actin, and β-tubulin expression levels during mouse postnatal development and suggests precautions when using these proteins as reference controls in cortical development studies.

Birth asphyxia-induced encephalopathy is a major cause of long-term neurological morbidity, including cognitive and motor deficits. A proposed treatment is maternal creatine supplementation for prophylactic neuroprotection. This study examined how maternal creatine supplementation with or without birth asphyxia affected the behaviour of spiny mice offspring.

Mounting evidence indicates that the cerebral cortical folding pattern conveys information relevant to brain function, as well as the developmental trajectory leading to the observed pattern at maturity. However, relatively little is known about the biomechanics of gyral and sulcal formation. Ferrets are a tractable animal model for studying folding, in which this process occurs over the first 40 days of postnatal life. Recently, high resolution magnetic resonance brain imaging data have been made available for a template representing 10 ferrets (5 male, 5 female) at 6 equally spaced time points ranging from postnatal day (P)8 to P38. In this study, local cerebral cortical thickness, curvature, and relative surface area are mapped onto cortical mid-thickness surface mesh models derived from the developmental template. Systematic comparisons between cortical growth and changes in curvature that accompany gyral and sulcal formation enable delineation of the sequence of changes of these anatomical characteristics during folding. The cerebral cortex is found to transition between two patterns of regionally varying cortical thickness. In early stages of gyral and sulcal formation, the cortex is relatively thick in regions destined to exhibit high magnitudes of surface curvature (folding), regardless of whether the region will become part of a gyrus or a sulcus. In the mature brain, a different regional pattern of thickness is achieved in which gyral cortex is thicker than sulcal cortex. Surface area expansion is also observed to relate to folding, as reflected in the regional pattern of surface curvature changes. Over a given developmental interval, changes in surface curvature are positively correlated with subsequent surface area expansion but negatively correlated with previous surface area expansion. Together, these comparisons lay out a sequence of growth and folding events. First, relative thickening of the cortex occurs in regions that will be gyral and sulcal at maturity. These regions undergo increases in curvature, facilitating surface area increases in the folded cortex. During the final phases of fold formation, the rate of thickness increase in gyri outpaces that in sulci.

Neuroinflammation plays a critical role in tissue injury and repair after neonatal hypoxic-ischemic (HI) brain injury and varies by sex. Growth differentiation factor-15 (GDF-15) is a cytokine released by macrophages during inflammation and is upregulated after brain ischemia. We examined the impact of GDF-15 knockout (KO) on volume loss and the combined microglia/macrophage response in the Rice-Vannucci model of neonatal HI injury.

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is an immune-mediated disease characterized by abrupt onset neurobehavioral changes. Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn's disease (CD), chronic conditions characterized by gastrointestinal inflammation. We describe eight individuals with both PANS and IBD.

The underlying neural and/or perceptual mechanisms of different visual illusions are still unknown; thus, they continue to be the focus of many ongoing studies. Inconsistencies persist in the empirical findings for understanding how the perception of these illusions evolves over the course of development.

This study was designed to examine whether social/environmental experiences can induce the epigenetic modification, and influence the associated physiology and behaviour. To test this, we have used social stress (prenatal stress [PNS]) model and then housed at environmental enrichment (EE) condition to evaluate the interaction between specific epigenetic modification and its influence on behaviour.

Homeobox genes are highly conserved and play critical roles in brain development. Recently, we have found that mammals have an additional fragment of approximately 20 amino acids in Emx1 and a poly-(AL)6-7 in Emx2, compared to other amniotes. It has been shown that Emx1 and Emx2 have synergistic actions in the brain development. These reports raise an interesting issue whether the differences of Emx1 and Emx2 between mammals and non-mammals are concerned with the organization and evolution of amniote pallium.

This study aimed to explore the impact and mechanism of Scutellariae radix (SR), dried root of Scutellaria baicalensis Georgi of Labiatae, on prenatal stress (PS)-induced anxiety-like and depression-like behavior in the offspring in a mouse prenatal stress model.

Brain cholesterol relies on de novo biosynthesis and is crucial for brain development. Cholesterol synthesis is a complex series of reactions that involves more than twenty enzymes to reach the final product and generates a large number of intermediate sterols along two alternate pathways. This is a highly regulated and oxygen-dependent process and thus sensitive to hypoxia.

In contemporary medical practice, general anesthesia plays an essential role in pediatric surgical procedures. While modern anesthetic protocols have demonstrated safety and efficacy across various pathological conditions, concerns persist regarding the potential neurotoxic effects associated with early exposure to general anesthesia.

Sevoflurane is an extensively used anesthetic for pediatric patients; however, numerous studies showed that sevoflurane (SEVO) may cause long-term neurodevelopmental toxicity. Dexmedetomidine (DEX) has been shown to be protective against SEVO-induced neurotoxicity, but the mechanism remains unclear. The effects and mechanisms of different DEX administration routes on SEVO-induced neurotoxicity and long-term cognitive defects were determined and further investigated the role of sex in these processes.

Pubertal maturation is marked by significant changes in stress-induced hormonal responses mediated by the hypothalamic-pituitary-adrenal (HPA) axis, with prepubertal male and female rats often exhibiting greater HPA reactivity compared to adult males and females. Though the implications of these changes are unclear, elevated stress responsiveness might contribute to the stress-related vulnerabilities often associated with puberty.

The fetal brain undergoes a dynamic process of development during gestation, marked by well-orchestrated events such as neuronal proliferation, migration, axonal outgrowth, and dendritic arborization, mainly elucidated through histological studies. Ex vivo magnetic resonance imaging (MRI) has emerged as a useful tool for 3D visualization of the developing fetal brain, serving as a complementary tool to traditional histology.