Defining longer term outcomes in an ovine model of moderate perinatal hypoxia-ischemia
Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 1 million infants born with HIE each year survive with cerebral palsy (CP) and/or serious cognitive disabilities. While infants born with mild and severe HIE frequently result in predictable outcomes, infants born with moderate HIE exhibit variable outcomes that are highly unpredictable. Here, we describe an umbilical cord occlusion (UCO) model of moderate HIE with a 6-day follow-up. Near term lambs (n=27) are resuscitated after the induction of 5 minutes of asystole. Following recovery, lambs are assesse...
Source: Developmental Neuroscience - May 19, 2022 Category: Neuroscience Source Type: research

Perineuronal Nets Degradation and Parvalbumin Interneuron loss in a Mouse Model of DEPDC5-related Epilepsy
DEPDC5, the key gene within the mechanistic target of rapamycin (mTOR) pathway, is one of the most common causative genes in patients with epilepsy and malformation of cortical development (MCD). Although somatic mutations in the dorsal cortical progenitors generate the malformed cortex, its pathogenesis of hyperexcitability is complex and remains unclear. We specifically deleted Depdc5 in the mouse forebrain dorsal progenitors to model DEPDC5-related epilepsy, and investigated whether and how parvalbumin interneurons were non-cell autonomously affected in the malformed cortex. We showed that long before seizures, coincide...
Source: Developmental Neuroscience - May 17, 2022 Category: Neuroscience Source Type: research

The Stem Cell Potential of O-2A Lineage Astroglia
In this study, we demonstrated that NSLCs grown in the serum-containing neurobasal medium can differentiate into induced neural-like cells (iNLCs). It was noteworthy that astroglia mixed in these cells, particularly in iNLCs, were gradually replaced by neural phenotypes during this glia-neuron conversion. Remarkably, these glial cells can maintain high levels of proliferation and self-renewal ability by activating the NF- κB and MAPK signals. Finally, we found that Notch, STAT3, autophagy, bHLH and Wnt signals appear to be critical modulators of these intricate events. Altogether, these data demonstrate that O-2A lineage ...
Source: Developmental Neuroscience - May 10, 2022 Category: Neuroscience Source Type: research

Multiple Early-life Seizures Alters Neonatal Communicative Behavior in Fmr1 Knockout Mice
Fragile X syndrome (FXS) is the leading monogenic cause of intellectual disability and a significant contributor to Autism Spectrum Disorder. Individuals with FXS are subject to developing numerous comorbidities, one of the most prevalent being seizures. In the present study, we investigated how seizures affected neonatal communicative behavior in the FXS mouse model. On postnatal day (PD) 7 through 11, we administered 3 flurothyl seizures per day to both Fmr1 knockout and wildtype C57BL/6J male mice. Ultrasonic vocalizations were recorded on PD12. Statistically significant alterations were found in both spectral and tempo...
Source: Developmental Neuroscience - May 5, 2022 Category: Neuroscience Source Type: research

Differential effects of Urban Particulate Matter on BV2 microglial-like and C17.2 neural stem/precursor cells
Air pollution affects the majority of the world ’s population and has been linked to over 7 million premature deaths per year. Exposure to particulate matter (PM) contained within air pollution is associated with cardiovascular, respiratory and neurological ill health. There is increasing evidence that exposure to air pollution in utero and in early childhood is associated with altered brain development. However, the underlying mechanisms for impaired brain development are not clear. While oxidative stress and neuroinflammation are documented consequences of PM exposure, cell-specific mechanisms that may be triggered in ...
Source: Developmental Neuroscience - May 2, 2022 Category: Neuroscience Source Type: research

Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adult Rats with Preterm Brain Injury
Cerebral palsy (CP) is the most common cause of physical disability for children worldwide. Many infants and toddlers are not diagnosed with CP until they fail to achieve obvious motor milestones. Currently, there are no effective pharmacologic interventions available for infants and toddlers to substantially improve their trajectory of neurodevelopment. Because children with CP from preterm birth also exhibit a sustained immune system hyper-reactivity, we hypothesized that neuro-immunomodulation with a regimen of repurposed endogenous neurorestorative medications, erythropoietin (EPO) and melatonin (MLT), could improve th...
Source: Developmental Neuroscience - March 31, 2022 Category: Neuroscience Source Type: research

Infantile Cocktail of Erythropoietin and Melatonin Restores Gait in Adults Rats with Preterm Brain Injury
Cerebral palsy (CP) is the most common cause of physical disability for children worldwide. Many infants and toddlers are not diagnosed with CP until they fail to achieve obvious motor milestones. Currently, there are no effective pharmacologic interventions available for infants and toddlers to substantially improve their trajectory of neurodevelopment. Because children with CP from preterm birth also exhibit a sustained immune system hyper-reactivity, we hypothesized that neuro-immunomodulation with a regimen of repurposed endogenous neurorestorative medications, erythropoietin (EPO) and melatonin (MLT) could improve thi...
Source: Developmental Neuroscience - March 31, 2022 Category: Neuroscience Source Type: research

Short juvenile stress has no long-lasting effects on anxiety-like behavior, object recognition memory, or gross brain morphology but affects dendritic spines in the hippocampus in male rats
Conclusion: Short-term and daily restraint and predator stress during the juvenile stage had no long-lasting effects on anxiety-like behavior, object memory, volume of the corpus callosum or hippocampus, or perirhinal cortex thickness, but a decrease in dendritic spine density was found in the hippocampus. These findings suggest that different types of stressors have different impacts on microstructures in the brain without affecting behavior or the gross morphology of stress-sensitive brain areas. (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 14, 2022 Category: Neuroscience Source Type: research

An optimized and detailed step-by-step protocol for the analysis of neuronal morphology in golgi-stained fetal sheep brain
We describe the step-by-step protocol to retrieve neuronal morphometrics using Imaris imaging software to provide quantification of apical and basal dendrites for measures of dendrite length ( μm), branch number, branch order and Sholl analysis (intersections over radius). We also detail software add-ons for data retrieval of dendritic spines including the number of spines, spine density and spine classification, which are critical indicators of synaptic function. The assessment of neuro nal morphology in the developing brain using Rapid-Golgi and Imaris software is labour-intensive, particularly during the optimization p...
Source: Developmental Neuroscience - March 11, 2022 Category: Neuroscience Source Type: research

Deficits in seizure threshold and other behaviors in adult mice without gross neuroanatomic injury after late gestation transient prenatal hypoxia
This study demonstrates that late gestation transient prenatal hypoxia in mice is a simple, clinically relevant paradigm for studying putative environmental and genetic modulators of the long-term effects of hypoxia on the developing brain. (Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 11, 2022 Category: Neuroscience Source Type: research

Brain outcomes in runted piglets: a translational model of fetal growth restriction
etal growth restriction (FGR) is associated with long-term neurodevelopmental disabilities including learning and behavioural disorders, autism, and cerebral palsy. Persistent changes in brain structure and function that are associated with developmental disabilities are demonstrated in FGR neonates. However, the mechanisms underlying these changes remain to be determined. There are currently no therapeutic interventions available to protect the FGR newborn brain. With the wide range of long-term neurodevelopmental disorders associated with FGR, the use of an animal model appropriate to investigating mechanisms of injury i...
Source: Developmental Neuroscience - March 9, 2022 Category: Neuroscience Source Type: research

The Vannucci Model of Hypoxic-Ischemic Injury in the Neonatal Rodent: 40 years later
Perinatal hypoxic-ischemic (HI) brain damage has long been a major cause of acute mortality and chronic neurologic morbidity in infants and children. Experimental animal models are essential to gain insights into the pathogenesis and management of perinatal HI brain damage. Prior to 1980 only large animal models were available. The first small animal model was developed in the postnatal 7 (P7) rat in 1981, now known as the Vannucci model. This model combines unilateral carotid artery ligation with subsequent hypoxia to produce transient hemispheric hypoxia-ischemia in the hemisphere ipsilateral to the ligation while the co...
Source: Developmental Neuroscience - March 9, 2022 Category: Neuroscience Source Type: research

Expression analyses of Cep152, a responsible gene product for autosomal recessive primary microcephaly, during mouse brain development
In this study, we prepared an antibody against mouse Cep152, anti-Cep152, and performed expression analyses focusing on mouse brain development. Western blotting analyses revealed that Cep152 with a molecular mass of ~150 kDa was expressed strongly at embryonic day (E) 13 and then gradually decreased during the brain development process. Instead, protein bands of ~80 kDa and ~60 kDa came to be recognized after postnatal day (P)15 and P30, respectively. In immunohistochemical analyses, Cep152 was enriched in the centrosome of neuronal progenitors in the ventricular zone at E14, whereas it was diffusely distributed mainly in...
Source: Developmental Neuroscience - March 8, 2022 Category: Neuroscience Source Type: research

Research Progress of Collapse Response Mediator Proteins in Neurodegenerative Diseases
(Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 4, 2022 Category: Neuroscience Source Type: research

Association Between Multi-Organ Involvement and Brain Injury in Cooled Newborns: A Statistical Approach
(Source: Developmental Neuroscience)
Source: Developmental Neuroscience - March 2, 2022 Category: Neuroscience Source Type: research