Maternal n-3 enriched diet reprograms the offspring neurovascular transcriptome and blunts inflammation induced by endotoxin in the neonate.

Infection during the perinatal period can adversely affect brain development, predispose infants to ischemic stroke and have lifelong consequences. We previously demonstrated that diet enriched in n-3 polyunsaturated fatty acids (n-3 PUFA) transforms brain lipid composition in the offspring and protects the neonatal brain from stroke, in part by blunting injurious immune responses. Critical to the interface between the brain and systemic circulation is the vasculature, endothelial cells in particular, that support brain homeostasis and provide a barrier to systemic infection.

Maternal n-3 enriched diet reprograms neurovascular transcriptome and blunts inflammation in neonate.

Infection during perinatal period can adversely affect brain development, predispose infants to ischemic stroke and have lifelong consequences. We previously demonstrated that diet enriched in n-3 polyunsaturated fatty acids (PUFA) transforms brain lipid composition and protects from neonatal stroke. Vasculature is a critical interface between blood and brain providing a barrier to systemic infection.

Therapeutic Effect of Nicotinamide Mononucleotide for Hypoxic-Ischemic Brain Injury in Neonatal Mice.

Neonatal hypoxia-ischemia reduces nicotinamide adenine dinucleotide (NAD) and SIRT6 levels in the injured hippocampus.Hippocampal high mobility group box-1 (HMGB1) release is significantly increased after neonatal hypoxia-ischemia.Nicotinamide mononucleotide (NMN) treatment normalizes hippocampal NAD and SIRT6 levels, with significant decrease in caspase-3 activity and HMGB1 release.

Proteomics identifies lipocalin-2 in neonatal inflammation associated with cerebrovascular alteration in mice and preterm infants.

is the most common nosocomial coagulase-negative staphylococci infection in preterm infants. Clinical signs of infection are often unspecific and novel markers to complement diagnosis are needed. We investigated proteomic alterations in mouse brain after infection and in preterm infant blood.

Transcriptome network analysis links perinatal Staphylococcus epidermidis infection to microglia reprogramming in the immature hippocampus.

Staphylococcus epidermidis (S. epidermidis) is the most common nosocomial pathogen in preterm infants and associated with increased risk of cognitive delay, however, underlying mechanisms are unknown. We employed morphological, transcriptomic and physiological methods to extensively characterize microglia in the immature hippocampus following S.

Sex-Dependent Gliovascular Interface Abnormality in the Hippocampus following Postnatal Immune Activation in Mice.

The neuro-gliovascular unit is a crucial structure for providing a balanced well-functioning environment for neurons and their synapses. Activation of the immune system during the developmental period is believed to affect the gliovascular unit, which may trigger neurodevelopmental and neurological/neuropsychiatric diseases. In this study, we hypothesized that vulnerability of the male brain to a neonatal insult was conditioned by sex-dependent differences in the impairment of the hippocampal gliovascular unit.

Reelin cells and sex-dependent synaptopathology in autism following postnatal immune activation.

Background And Purpose: Autism spectrum disorders (ASD) are heterogeneous neurodevelopmental disorders with considerably increased risk in male infants born preterm and with neonatal infection. Here, we investigated the role of postnatal immune activation on hippocampal synaptopathology by targeting Reelin+ cells in mice with ASD-like behaviours.

Experimental Approach: C57/Bl6 mouse pups of both sexes received lipopolysaccharide (LPS, 1 mg·kg ) on postnatal day (P) 5.

N-Acetyl Cysteine Restores Sirtuin-6 and Decreases HMGB1 Release Following Lipopolysaccharide-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Mice.

Inflammation and neonatal hypoxia-ischemia (HI) are important etiological factors of perinatal brain injury. However, underlying mechanisms remain unclear. Sirtuins are a family of nicotinamide adenine dinucleotide (NAD)+-dependent histone deacetylases.

Maternal n-3 Polyunsaturated Fatty Acid Enriched Diet Commands Fatty Acid Composition in Postnatal Brain and Protects from Neonatal Arterial Focal Stroke.

The fetus is strongly dependent on nutrients from the mother, including polyunsaturated fatty acids (PUFA). In adult animals, n-3 PUFA ameliorates stroke-mediated brain injury, but the modulatory effects of different PUFA content in maternal diet on focal arterial stroke in neonates are unknown. This study explored effects of maternal n-3 or n-6 enriched PUFA diets on neonatal stroke outcomes.

Viral mimetic triggers cerebral arteriopathy in juvenile brain via neutrophil elastase and NETosis.

Stroke is among the top ten causes of death in children but has received disproportionally little attention. Cerebral arteriopathies account for up to 80% of childhood arterial ischemic stroke (CAIS) cases and are strongly predictive of CAIS recurrence and poorer outcomes. The underlying mechanisms of sensitization of neurovasculature by viral infection are undefined.

Overexpression of under the Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus.

The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse () expressing under the promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these mice.

Type 2 Innate Lymphoid Cells Accumulate in the Brain After Hypoxia-Ischemia but Do Not Contribute to the Development of Preterm Brain Injury.

Background: The immune system of human and mouse neonates is relatively immature. However, innate lymphoid cells (ILCs), commonly divided into the subsets ILC1, ILC2, and ILC3, are already present in the placenta and other fetal compartments and exhibit higher activity than what is seen in adulthood. Recent reports have suggested the potential role of ILCs, especially ILC2s, in spontaneous preterm labor, which is associated with brain damage and subsequent long-term neurodevelopmental deficits.

Flinders sensitive line rats are resistant to infarction following transient occlusion of the middle cerebral artery.

Background: Depression is a common complication of stroke and increases the risk of mortality and disability. Pre-stroke depression is a possible risk factor for stroke and has also been linked to adverse outcomes. The underlying mechanisms linking depression and stroke remain unclear.

Sex-Dependent Effects of Perinatal Inflammation on the Brain: Implication for Neuro-Psychiatric Disorders.

Individuals born preterm have higher rates of neurodevelopmental disorders such as schizophrenia, autistic spectrum, and attention deficit/hyperactivity disorders. These conditions are often sexually dimorphic and with different developmental trajectories. The etiology is likely multifactorial, however, infections both during pregnancy and in childhood have emerged as important risk factors.

Neurod1 Is Essential for the Primary Tonotopic Organization and Related Auditory Information Processing in the Midbrain.

Hearing depends on extracting frequency, intensity, and temporal properties from sound to generate an auditory map for acoustical signal processing. How physiology intersects with molecular specification to fine tune the developing properties of the auditory system that enable these aspects remains unclear. We made a novel conditional deletion model that eliminates the transcription factor NEUROD1 exclusively in the ear.

Age-Related Differences in Hearing Function and Cochlear Morphology between Male and Female Fischer 344 Rats.

Fischer 344 (F344) rats represent a strain that is frequently used as a model for fast aging. In this study, we systematically compare the hearing function during aging in male and female F344 rats, by recording auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). In addition to this, the functional parameters are correlated with the cochlear histology.

Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders.

The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function.

Incomplete and delayed Sox2 deletion defines residual ear neurosensory development and maintenance.

The role of Sox2 in neurosensory development is not yet fully understood. Using mice with conditional Islet1-cre mediated deletion of Sox2, we explored the function of Sox2 in neurosensory development in a model with limited cell type diversification, the inner ear. In Sox2 conditional mutants, neurons initially appear to form normally, whereas late- differentiating neurons of the cochlear apex never form.

Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation.

The programming of cell fate by transcription factors requires precise regulation of their time and level of expression. The LIM-homeodomain transcription factor Islet1 (Isl1) is involved in cell-fate specification of motor neurons, and it may play a similar role in the inner ear. In order to study its role in the regulation of vestibulo-motor development, we investigated a transgenic mouse expressing Isl1 under the Pax2 promoter control (Tg ).

Cooling of the auditory cortex modifies neuronal activity in the inferior colliculus in rats.

There are powerful pathways descending from the auditory cortex (AC) to the inferior colliculus (IC), yet their function is not fully understood. The aim of this study is to examine the effects of a reversible cortical inactivation, achieved by cooling of the AC, on the responses of neurons in the rat IC. Extracellular single-unit or multi-unit activity was recorded in the IC of anaesthetized rats with a 16-channel multielectrode probe introduced along the IC dorso-ventral axis through the dorsal cortex (DCIC) to the central nucleus of the IC (CIC).

Human Multipotent Mesenchymal Stromal Cells in the Treatment of Postoperative Temporal Bone Defect: An Animal Model.

Canal wall down mastoidectomy is one of the most effective treatments for cholesteatoma. However, it results in anatomical changes in the external and middle ear with a negative impact on the patient's quality of life. To provide complete closure of the mastoid cavity and normalize the anatomy of the middle and external ear, we used human multipotent mesenchymal stromal cells (hMSCs), GMP grade, in a guinea pig model.

BDNF in Lower Brain Parts Modifies Auditory Fiber Activity to Gain Fidelity but Increases the Risk for Generation of Central Noise After Injury.

For all sensory organs, the establishment of spatial and temporal cortical resolution is assumed to be initiated by the first sensory experience and a BDNF-dependent increase in intracortical inhibition. To address the potential of cortical BDNF for sound processing, we used mice with a conditional deletion of BDNF in which Cre expression was under the control of the Pax2 or TrkC promoter. BDNF deletion profiles between these mice differ in the organ of Corti (BDNF (Pax2) -KO) versus the auditory cortex and hippocampus (BDNF (TrkC) -KO).

Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice.

The development, maturation, and maintenance of the inner ear are governed by temporal and spatial expression cascades of transcription factors that form a gene regulatory network. ISLET1 (ISL1) may be one of the major players in this cascade, and in order to study its role in the regulation of inner ear development, we produced a transgenic mouse overexpressing Isl1 under the Pax2 promoter. Pax2-regulated ISL1 overexpression increases the embryonic ISL1(+) domain and induces accelerated nerve fiber extension and branching in E12.

Development of the acoustic startle response in rats and its change after early acoustic trauma.

Even brief acoustic trauma during the critical period of development that results in no permanent hearing threshold shift may lead to altered auditory processing in adulthood. By monitoring the acoustic startle response (ASR), we examined the development of auditory function in control rats and in rats exposed to intense noise at the 14th postnatal day (P14). First ASRs appeared on P10-P11 to intense low-frequency tones.

Acoustical enrichment during early postnatal development changes response properties of inferior colliculus neurons in rats.

The structure and function of the auditory system may be influenced by acoustic stimulation, especially during the early postnatal period. This study explores the effects of an acoustically enriched environment applied during the third and fourth week of life on the responsiveness of inferior colliculus neurons in rats. The enrichment comprised a spectrally and temporally modulated complex sound reinforced with several target acoustic stimuli, one of which triggered a reward release.