Brain Perfusion Is Increased at Term in the White Matter of Very Preterm Newborns and Newborns with Congenital Heart Disease: Does this Reflect Activated Angiogenesis?

Objective: This study aims to evaluate brain perfusion at term in very preterm newborns and newborns with congenital heart disease before their corrective surgery, and to search for histopathological indicators of whether the brain perfusion abnormalities of these newborns may be related to an activated angiogenesis.

Materials And Methods: Using magnetic resonance imaging and arterial spin labeling, regional cerebral blood flow was measured at a term-equivalent age for three very preterm newborns (born at < 32 weeks), one newborn with congenital heart disease before his corrective surgery and three healthy newborns. In addition, a histopathological analysis was performed on a newborn with congenital heart disease.

Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis?

Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia.

α5-GABAA receptors negatively regulate MYC-amplified medulloblastoma growth.

Neural tumors often express neurotransmitter receptors as markers of their developmental lineage. Although these receptors have been well characterized in electrophysiological, developmental and pharmacological settings, their importance in the maintenance and progression of brain tumors and, importantly, the effect of their targeting in brain cancers remains obscure. Here, we demonstrate high levels of GABRA5, which encodes the α5-subunit of the GABAA receptor complex, in aggressive MYC-driven, "Group 3" medulloblastomas.

Perfusion Imaging of Focal Cortical Dysplasia Using Arterial Spin Labeling: Correlation With Histopathological Vascular Density.

Focal cortical dysplasia is the most common malformation of cortical development, causing intractable epilepsy. This study investigated the relationship between brain perfusion and microvessel density in 7 children with focal cortical dysplasia. The authors analyzed brain perfusion measurements obtained by magnetic resonance imaging of 2 of the children and the microvessel density of brain tissue specimens obtained by epilepsy surgery on all of the children.

Mammalian target of rapamycin complex 1 activation negatively regulates Polo-like kinase 2-mediated homeostatic compensation following neonatal seizures.

Homeostatic plasticity is characterized by compensatory changes in synaptic strength and intrinsic membrane properties in response to chronic changes in neuronal activity. Neonatal seizures are a naturally occurring source of neuronal overactivation and can lead to long-term epilepsy and cognitive deficits. Using a rodent model of hypoxia-induced neonatal seizures that results in a persistent increase in AMPA receptor (AMPAR) function in hippocampal CA1 pyramidal neurons, we aimed to determine whether there was any evidence of an opposing endogenous homeostatic antiepileptic response.

Antiepileptic effects of levetiracetam in a rodent neonatal seizure model.

Background: Neonatal seizures can result in chronic epilepsy and long-term behavioral and cognitive deficits. Levetiracetam (LEV), an antiepileptic drug that binds to the synaptic vesicle protein 2A (SV2A), has been increasingly used off-label for the therapy of neonatal seizures. Preclinical data regarding the acute or long-term efficacy of LEV are lacking.

Altered inhibition in tuberous sclerosis and type IIb cortical dysplasia.

Objective: The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered γ-aminobutyric acid (GABA)(A) receptor (GABA(A)R)-mediated inhibition.

Methods: Expression of the GABA(A)R subunits α1 and α4, and the Na(+)-K(+)-2Cl(-) (NKCC1) and the K(+)-Cl(-) (KCC2) transporters, in human TSC and FCD type II specimens were analyzed by Western blot and double label immunocytochemistry.

Development of later life spontaneous seizures in a rodent model of hypoxia-induced neonatal seizures.

Purpose: To study the development of epilepsy following hypoxia-induced neonatal seizures in Long-Evans rats and to establish the presence of spontaneous seizures in this model of early life seizures.

Methods: Long-Evans rat pups were subjected to hypoxia-induced neonatal seizures at postnatal day 10 (P10). Epidural cortical electroencephalography (EEG) and hippocampal depth electrodes were used to detect the presence of seizures in later adulthood (> P60).

Modulation of lipid peroxidation and mitochondrial function improves neuropathology in Huntington's disease mice.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Oxidative damage has been associated with pathological neuronal loss in HD. The therapeutic modulation of oxidative stress and mitochondrial function using low molecular weight compounds may be an important strategy for delaying the onset and slowing the progression of HD.

Sensory innervation of the calvarial bones of the mouse.

Migraine sufferers frequently testify that their headache feels as if the calvarial bones are deformed, crushed, or broken (Jakubowski et al. [2006] Pain 125:286-295). This has lead us to postulate that the calvarial bones are supplied by sensory fibers.

T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS.

Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease, in which the role of inflammation is not well established. Innate and adaptive immunity were investigated in the CNS of the Superoxide Dismutase 1 (SOD1)(G93A) transgenic mouse model of ALS. CD4+ and CD8+ T cells infiltrated SOD1(G93A) spinal cords during disease progression.

Myelin structure and composition of myelinated tissue in the African lungfish.

To analyze myelin structure and the composition of myelinated tissue in the African lungfish (Protopterus dolloi), we used a combination of ultrastructural and biochemical techniques. Electron microscopy showed typical multilamellar myelin: CNS sheaths abutted one another, and PNS sheaths were separated by endoneurial collagen. The radial component, prominent in CNS myelin of higher vertebrates, was suggested by the pattern of staining but was poorly organized.

Toll-like receptor 3 is a potent negative regulator of axonal growth in mammals.

Toll is a cell surface receptor with well described roles in the developmental patterning of invertebrates and innate immunity in adult Drosophila. Mammalian toll-like receptors represent a family of Toll orthologs that function in innate immunity by recognizing molecular motifs unique to pathogens or injured tissue. One member in this family of pattern recognition receptors, toll-like receptor 3 (TLR3), recognizes viral double-stranded RNA and host mRNA.

Toll-like receptor 8 functions as a negative regulator of neurite outgrowth and inducer of neuronal apoptosis.

Toll receptors in Drosophila melanogaster function in morphogenesis and host defense. Mammalian orthologues of Toll, the Toll-like receptors (TLRs), have been studied extensively for their essential functions in controlling innate and adaptive immune responses. We report that TLR8 is dynamically expressed during mouse brain development and localizes to neurons and axons.

Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response.

Cyclooxygenase-2 (COX-2) has been implicated in neuronal survival and death. However, the precise regulatory mechanisms involved in COX-2 function are unclear. In the present study we found that COX-2 is induced in response to glutathione depletion-induced oxidative stress in primary cortical neurons.

WAVE1 is required for oligodendrocyte morphogenesis and normal CNS myelination.

Myelin formation involves the outgrowth of an oligodendrocyte cell process that can be regarded as a giant lamellipodium because it is an actively growing structure with extruded cytoplasm. The actin cytoskeleton is critical to morphogenesis, but little is known about regulation of actin dynamics in oligodendrocytes. Wiskott-Aldrich syndrome protein family verprolin homologous (WAVE) proteins mediate lamellipodia formation; thus, we asked whether these proteins function in oligodendrocyte process formation and myelination.

Atm-, p53-, and Gadd45a-deficient mice show an increased frequency of homologous recombination at different stages during development.

Atm, p53, and Gadd45a form part of a DNA-damage cellular response pathway; the absence of any one of these components results in increased genomic instability. We conducted an in vivo examination of the frequency of spontaneous homologous recombination in Atm-, p53-, or Gadd45a-deficient mice. In the absence of p53, we observed the greatest increase in events, a lesser increase in the absence of Atm, and only a modest increase in the absence of Gadd45a.