Developmental neuroscience
-
Abnormal development of the cerebellum is often associated with disorders of movement, postural control, and motor learning. Rodent models are widely used to study normal and abnormal cerebellar development and have revealed the roles of many important genetic and environmental factors. ⋯ Heterotopia were not observed in a sample of wild-derived mice, outbred mice, or inbred mice not closely related to C57BL/6 mice. These data are relevant to the use of C57BL/6 mice as models in the study of brain and behavior relationships and provide greater understanding of human cerebellar dysplasia.
-
Traumatic brain injury in children commonly involves the frontal lobes and is associated with distinct structural and behavioral changes. Despite the clinical significance of injuries localized to this region during brain development, the mechanisms underlying secondary damage and long-term recovery are poorly understood. Here, we have characterized the first model of unilateral focal traumatic injury to the developing frontal lobe. ⋯ The signature phenotypic features were deficits in motor function and motor learning, coincident with a reduction in ipsilateral cortical brain volumes. Together, these findings demonstrate classic morphological features of a focal traumatic injury, including early cell death and axonal injury, and long-term volumetric loss of cortical volumes. The presence of deficits in sensorimotor function and coordination in the absence of abnormal findings related to anxiety, sociability and memory likely reflects several variables, including the unique location of the injury and the emergence of favorable compensatory mechanisms during subsequent brain development.
-
Hypothermia is known to improve neurological recovery of animals and humans exposed to hypoxic-ischemic (HI) injury. However, the underlying mechanisms of the neuroprotective effects of hypothermia are only partially understood, including decreased excitotoxicity and apoptosis, and suppressed inflammation. There are few studies about the hypothermic effects on axonal injury and oligodendrocyte (OL) lineage degeneration, which are important components of neonatal brain injuries that cause cognitive disability. ⋯ Axonal myelination also increased in hypothermic animals, which were tested by myelin basic protein and NF200 double staining and electron microscopy. These results showed that hypothermia reduced HI damage to axons and OL myelination coincided with increased early OL progenitor proliferation and decreased preOL accumulation and apoptosis. This study suggested new aspects that may contribute to elucidate the mechanism of hypothermic neuroprotection in neonatal rat brain.
-
Neonatal encephalopathy induced by perinatal asphyxia is a serious condition associated with high mortality and morbidity. Inflammation after the insult is thought to contribute to brain injury. This inflammatory response to hypoxia-ischemia (HI) may not only occur in the brain but also in peripheral organs. The aim of the present study was to investigate the effect of neonatal HI on the inflammatory response in the liver in comparison to inflammation in the brain. ⋯ We describe for the first time that brain damage following neonatal HI induces an early downregulation of the proinflammatory response in the liver. HI induces an early proinflammatory response in the brain with a concomitant increase in influx of neutrophils and polarization of macrophages/microglia to the M1-like phenotype starting at 3 h and increasing up to 24 h after HI. The inflammatory state of the brain changes after 24 h, with an increase in the anti-inflammatory cytokine TGF-β together with the appearance of macrophages/microglia of the M2-like phenotype. The downregulation of proinflammatory cytokines in the liver is not due to systemic hypoxia only, but is induced by the cerebral damage.
-
Fragile X syndrome (FXS), due to transcriptional silencing of fragile X mental retardation protein (FMRP), is characterized by excess synaptic connections and impaired dendrite maturation. Programmed cell death (PCD) is critical for synaptogenesis and elimination of aberrant neuronal connections in the developing brain; however, the role of FMRP in PCD is unknown. The aim of this work was to assess the intrinsic apoptosis pathway in the developing brain of Fmr1 mutants. ⋯ Taken together, the data suggest that PCD is impaired due to increased BCL-xL expression and is associated with excess neurons in the developing brain of FMRP-deficient mice. It is possible that deficient PCD prevents neuron elimination and results in abnormal retention of developmentally transient neurons. Thus, defective PCD may contribute to the excess synaptic connections known to exist in Fmr1 mutants and could play a role in the behavioral phenotype of children with FXS.