Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant. One of the most important long-term complications observed in children who survive NEC early in life is the development of profound neurological impairments. However, the pathways leading to NEC-associated neurological impairments remain unknown, thus limiting the development of prevention strategies. We have recently shown that NEC development is dependent on the expression of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) on the intestinal epithelium, whose activation by bacteria in the newborn gut leads to mucosal inflammation. Here, we hypothesized that damage-induced production of TLR4 endogenous ligands in the intestine might lead to activation of microglial cells in the brain and promote cognitive impairments. We identified a gut-brain signaling axis in an NEC mouse model in which activation of intestinal TLR4 signaling led to release of high-mobility group box 1 in the intestine that, in turn, promoted microglial activation in the brain and neurological dysfunction. We further demonstrated that an orally administered dendrimer-based nanotherapeutic approach to targeting activated microglia could prevent NEC-associated neurological dysfunction in neonatal mice. These findings shed light on the molecular pathways leading to the development of NEC-associated brain injury, provide a rationale for early removal of diseased intestine in NEC, and indicate the potential of targeted therapies that protect the developing brain in the treatment of NEC in early childhood.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170511 | PMC |
http://dx.doi.org/10.1126/scitranslmed.aan0237 | DOI Listing |
Cereb Cortex
December 2024
Department of Neurology, Xuanwu Hospital of Capital Medical University, #45 Changchun Street, Xicheng District, Beijing 100053, China.
The asymmetric pattern of β-amyloid plaque distribution across Alzheimer's disease clinical progression stages remains unclear. In this study, 66 participants with normal cognition, 59 with subjective cognitive decline, 12 with mild cognitive impairment, and 11 with Alzheimer's disease dementia were included in the Sino Longitudinal Study on Cognitive Decline (SILCODE) cohort. A regional asymmetry index, denoting the left-right asymmetry of β-amyloid plaques, was derived for each region based on the Anatomical Automatic Labeling atlas.
View Article and Find Full Text PDFPhysiol Behav
December 2024
Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Cognitive Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. Electronic address:
Objectives: This study investigated the effects of environmental enrichment (EE) on the behavior and histological alterations of rats with barrel cortex damage.
Methods: Forty-eight adult male rats were divided into Control (Ctrl), Lesion, Lesion+EE.S (Lesion+Standard Enriched Environment, and Lesion+EE.
Eur J Pediatr
December 2024
Dept. of Research and Development, SeysCentra, Malden, The Netherlands.
Unlabelled: Children with Noonan syndrome-like RASopathies are at increased risk for developing feeding problems due to comorbid organic impairments at an early age, such as gastrointestinal problems or other organicity. Their feeding problems can ultimately often be classified as avoidant/restrictive food intake disorder, for which behavioral therapy is the first-choice treatment. The research question in this study is whether this treatment leads to similar results as in children without these RASopathies.
View Article and Find Full Text PDFEur J Pediatr
December 2024
Division of Child Neurology, Department of Paediatrics, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey.
Unlabelled: Phenylalanine (PA) levels below 360 µmol/L do not require treatment; however, cognitive deficits have been observed in patients with elevated PA levels, necessitating a safe upper limit for treatment and therapeutic objectives. The main purpose of this study is to evaluate the correlation between developmental assessments (Denver Developmental Screening Test-II [DDST-II] and Ankara Developmental Screening Inventory [ADSI]) and electroencephalogram (EEG) findings with blood PA levels and genotypic data in non-phenylketonuria mild Hyperphenylalaninemia (HPA) patients, to re-evaluate their treatment status based on potential adverse outcomes. This study encompassed 40 patients aged 1-5 years diagnosed with HPA and not on treatment, identified through initial blood PA levels, and monitored for a minimum of 1 year on an unrestricted diet.
View Article and Find Full Text PDFJ Neuroeng Rehabil
December 2024
Section of Physiology, Laboratory of Neuro-Biomechanics, Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123, Catania, Italy.
Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, characterized by impairments in social interaction and communication with restricted and repetitive behavior. Postural and motor disturbances occur more often in ASD, in comparison to typically developing subjects, affecting the quality of life. Linear and non-linear indexes derived from the trajectory of the center of pressure (COP) while subjects stand on force platforms are commonly used to assess postural stability.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!