Hypoxic-ischemic (HI) brain injury in infants is a leading cause of lifelong disability. We report a novel pathway mediating oxidative brain injury after hypoxia-ischemia in which C1q plays a central role. Neonatal mice incapable of classical or terminal complement activation because of C1q or C6 deficiency or pharmacologically inhibited assembly of membrane attack complex were subjected to hypoxia-ischemia. Only C1q(-/-) mice exhibited neuroprotection coupled with attenuated oxidative brain injury. This was associated with reduced production of reactive oxygen species (ROS) in C1q(-/-) brain mitochondria and preserved activity of the respiratory chain. Compared with C1q(+/+) neurons, cortical C1q(-/-) neurons exhibited resistance to oxygen-glucose deprivation. However, postischemic exposure to exogenous C1q increased both mitochondrial ROS production and mortality of C1q(-/-) neurons. This C1q toxicity was abolished by coexposure to antioxidant Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid). Thus, the C1q component of complement, accelerating mitochondrial ROS emission, exacerbates oxidative injury in the developing HI brain. The terminal complement complex is activated in the HI neonatal brain but appeared to be nonpathogenic. These findings have important implications for design of the proper therapeutic interventions against HI neonatal brain injury by highlighting a pathogenic priority of C1q-mediated mitochondrial oxidative stress over the C1q deposition-triggered terminal complement activation.
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http://dx.doi.org/10.1523/JNEUROSCI.5249-09.2010 | DOI Listing |
Nat Commun
December 2024
Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Penetrating orocutaneous or oropharyngeal fistulas (POFs), severe complications following unsuccessful oral or oropharyngeal reconstruction, remain complex clinical challenges due to lack of supportive tissue, contamination with saliva and chewed food, and dynamic oral environment. Here, we present a Janus hydrogel adhesive (JHA) with asymmetric functions on opposite sides fabricated via a facile surface enzyme-initiated polymerization (SEIP) approach, which self-entraps surface water and blood within an in-situ formed hydrogel layer (RL) to effectively bridge biological tissues with a supporting hydrogel (SL), achieving superior wet-adhesion and seamless wound plugging. The tough SL hydrogel interlocked with RL dissipates energy to withstand external mechanical stimuli from continuous oral motions like chewing and swallowing, thus reducing stress-induced damage.
View Article and Find Full Text PDFBDJ Open
December 2024
Consultant in Special Care Dentistry, Surrey and Sussex NHS Health Care Trust, Redhill, UK.
Background: Dental treatment may not be possible for patients with a profound acquired brain injury without pharmacological support. Intravenous (IV) sedation with midazolam is a widely accepted, safe, and effective mode of treatment for people with a disability, but there is limited evidence in this patient cohort.
Aims: This evaluation aimed to review the IV sedation service for patients with profound acquired brain injury within the dental department at the Royal Hospital for Neuro-disability.
Clin Transl Med
January 2025
Institute of Clinical Pharmacy, Jining First People's Hospital, Shandong First Medical University, Jining, P.R. China.
Magn Reson Med
December 2024
Department of Radiology, Stanford University School of Medicine, Stanford, California, USA.
Purpose: To measure and validate elevated succinate in brain during circulatory arrest in a piglet model of cardiopulmonary bypass.
Methods: Using data from an archive of 3T H MR spectra acquired in previous in-magnet studies, dynamic plots of succinate, spectral simulations and difference spectra were generated for analysis and validation.
Results: Elevation of succinate during circulatory arrest was observed and validated.
Alzheimers Dement
December 2024
Department of Psychology, University of Bath, Bath, UK.
Introduction: White matter hyperintensity volumes (WMHVs) are disproportionally prevalent in individuals with Alzheimer's disease (AD), potentially reflecting neurovascular injury. We quantify the association between AD polygenic risk score (AD-PRS) and WMHV, exploring single-nucleotide polymorphisms (SNPs) that are proximal to genes overexpressed in cerebrovascular cell species.
Methods: In a UK-Biobank sub-sample (mean age = 64, range = 45-81 years), we associate WMHV with (1) AD-PRS estimated via SNPs across the genome (minus apolipoprotein E [APOE] locus) and (2) AD-PRS estimated with SNPs proximal to specific genes that are overexpressed in cerebrovascular cell species.
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