Correction: Optimization and characterization of miRNA-129-5p-encapsulated poly (lactic--glycolic acid) nanoparticles to reprogram activated microglia.

[This corrects the article DOI: 10.1039/D3NA00149K.].

Biodegradable nanoparticles targeting circulating immune cells reduce central and peripheral sensitization to alleviate neuropathic pain following spinal cord injury.

Neuropathic pain is a critical source of comorbidity following spinal cord injury (SCI) that can be exacerbated by immune-mediated pathologies in the central and peripheral nervous systems. In this article, we investigate whether drug-free, biodegradable, poly(lactide- co -glycolide) (PLG) nanoparticle treatment mitigates the development of post-SCI neuropathic pain in female mice. Our results show that acute treatment with PLG nanoparticles following thoracic SCI significantly reduces tactile and cold hypersensitivity scores in a durable fashion.

Postictal hypoxia involves reactive oxygen species and is ameliorated by chronic mitochondrial uncoupling.

Prolonged severe hypoxia follows brief seizures and represents a mechanism underlying several negative postictal manifestations without interventions. Approximately 50% of the postictal hypoxia phenomenon can be accounted for by arteriole vasoconstriction. What accounts for the rest of the drop in unbound oxygen is unclear.

Optimization and characterization of miRNA-129-5p-encapsulated poly (lactic--glycolic acid) nanoparticles to reprogram activated microglia.

Microglia have become a therapeutic target of many inflammation-mediated diseases in the central nervous system (CNS). Recently, microRNA (miRNA) has been proposed as an important regulator of immune responses. Specifically, miRNA-129-5p has been shown to play critical roles in the regulation of microglia activation.

Novel Isolation Method Reveals Sex-Specific Composition and Neurotoxicity of Small Extracellular Vesicles in a Mouse Model of Alzheimer's Disease.

We developed a new method to isolate small extracellular vesicles (sEVs) from male and female wild-type and 5xFAD mouse brains to investigate the sex-specific functions of sEVs in Alzheimer's disease (AD). A mass spectrometric analysis revealed that sEVs contained proteins critical for EV formation and Aβ. ExoView analysis showed that female mice contained more GFAP and Aβ-labeled sEVs, suggesting that a larger proportion of sEVs from the female brain is derived from astrocytes and/or more likely to bind to Aβ.

The reliability and validity of the TBI-CareQOL system in four diverse caregiver groups.

Purpose: Establishing the psychometric reliability and validity of new measures is an ongoing process. More work is needed in to confirm the clinical utility of the TBI-CareQOL measurement development system in both an independent cohort of caregivers of traumatic brain injury (TBI), as well as in additional caregiver groups.

Methods: An independent cohort of caregivers of people with TBI (n = 139), as well as three new diverse caregiver cohorts (n = 19 caregivers of persons with spinal cord injury, n = 21 caregivers for persons with Huntington disease, and n = 30 caregivers for persons with cancer), completed 11 TBI-CareQOL measures (caregiver strain; caregiver-specific anxiety; anxiety; depression; anger; self-efficacy; positive affect and well-being; perceived stress; satisfaction with social roles and activities; fatigue; sleep-related impairment), as well as two additional measures to examine convergent and discriminant validity (PROMIS Global Health; the Caregiver Appraisal Scale).

Efficacy of a group-based education intervention for people with traumatic brain injury: supplementary results from a 12-month randomized controlled trial.

Objective: Our team developed an attention control condition, called the Brain Health Group (BHG), for a randomized controlled trial (RCT; NCT03594734). The focus of the BHG was on brain health education and self-management. The objectives of this supplementary analysis are to (1) Describe compliance with the 12-month BHG; (2) Examine efficacy for improving general self-efficacy (GSE, primary) and secondary outcomes; and (3) Describe findings from the program evaluation.

Effects of Acute Ethanol Intoxication on Spinal Cord Injury Outcomes in Female Mice.

Approximately one in three traumatic spinal cord injuries (SCIs) occurs during or shortly after the consumption of alcohol. A small number of retrospective clinical studies report variable effects of alcohol intoxication on mortality, neurological recovery, and complications after SCI. Some of these studies demonstrate a protective effect of alcohol intoxication on SCI outcomes, whereas others show an increased complication risk.

Immunomodulatory Strategies for Spinal Cord Injury.

Neuroinflammation is a key secondary event after spinal cord injury (SCI) and can increase barriers to regeneration, leading to various neurological disorders. Infiltrated hematogenous innate immune cells into the injured site are considered the main effector cells of the inflammatory responses after SCI. Glucocorticoids were the standard of care for spinal cord trauma for years due to their anti-inflammatory properties yet were also associated with unwanted side effects.

Developing multidimensional participation profiles after traumatic brain injury: a TBI model systems study.

To characterize societal participation profiles after moderate-severe traumatic brain injury (TBI) along objective (Frequency) and subjective (Satisfaction, Importance, Enfranchisement) dimensions. We conducted secondary analyses of a TBI Model Systems sub-study ( = 408). Multiaxial assessment of participation included the Participation Assessment with Recombined Tools-Objective and -Subjective questionnaires (Participation Frequency and Importance/Satisfaction, respectively) and the Enfranchisement Scale.

An Umbrella Review of Self-Management Interventions for Health Conditions With Symptom Overlap With Traumatic Brain Injury.

Objective: To synthesize evidence for the effectiveness of self-management interventions for chronic health conditions that have symptom overlap with traumatic brain injury (TBI) in order to extract recommendations for self-management intervention in persons with TBI.

Design: An umbrella review of existing systematic reviews and/or meta-analyses of randomized controlled trials or nonrandomized studies targeting self-management of chronic conditions and specific outcomes relevant to persons with TBI.

Method: A comprehensive literature search of 5 databases was conducted using PRISMA guidelines.

The BDNF mimetic R-13 attenuates TBI pathogenesis using TrkB-related pathways and bioenergetics.

Traumatic brain injury (TBI) is major neurological burden globally, and effective treatments are urgently needed. TBI is characterized by a reduction in energy metabolism and synaptic function that seems a primary cause of neuronal dysfunction. R13, a small drug and BDNF mimetic showed promising results in improving spatial memory and anxiety-like behavior after TBI.

Serum-Stable Gold(III) Bisphosphine Complex Induces Mild Mitochondrial Uncoupling and In Vivo Antitumor Potency in Triple Negative Breast Cancer.

The preparation of cyclometalated complexes offers a path to stable materials, catalysts, and therapeutic agents. Here, we explore the anticancer potential of novel biphenyl organogold(III) cationic complexes supported by diverse bisphosphine ligands, , toward aggressive glioblastoma and triple negative breast cancer cells (TNBCs). The [C^C] gold(III) complex, , exhibits significant tumor growth inhibition in a metastatic TNBC mouse model.

The American Congress of Rehabilitation Medicine Diagnostic Criteria for Mild Traumatic Brain Injury.

Objective: To develop new diagnostic criteria for mild traumatic brain injury (TBI) that are appropriate for use across the lifespan and in sports, civilian trauma, and military settings.

Design: Rapid evidence reviews on 12 clinical questions and Delphi method for expert consensus.

Participants: The Mild Traumatic Brain Injury Task Force of the American Congress of Rehabilitation Medicine Brain Injury Special Interest Group convened a Working Group of 17 members and an external interdisciplinary expert panel of 32 clinician-scientists.

Impaired activity and membrane association of most calpain-5 mutants causal for neovascular inflammatory vitreoretinopathy.

Neovascular inflammatory vitreoretinopathy (NIV) is a rare eye disease that ultimately leads to complete blindness and is caused by mutations in the gene encoding calpain-5 (CAPN5), with six pathogenic mutations identified. In transfected SH-SY5Y cells, five of the mutations resulted in decreased membrane association, diminished S-acylation, and reduced calcium-induced autoproteolysis of CAPN5. CAPN5 proteolysis of the autoimmune regulator AIRE was impacted by several NIV mutations.

Spatial metabolomics reveals glycogen as an actionable target for pulmonary fibrosis.

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high-dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression.

Identification of Factors in Moderate-Severe TBI Related to a Functional Decline in Cognition Decades After Injury.

Objective: To investigate whether a functional decline in cognitive activities decades after moderate-to-severe traumatic brain injury (m-sTBI) might relate to injury features and/or lifetime health factors, some of which may emerge as consequences of the injury.

Design: Secondary analysis of the TBI Model Systems National Database, a prospective, multi-center, longitudinal study of patients with m-sTBI.

Setting: TBI Model Systems Centers.

Liver acts as a metabolic gate for the traumatic brain injury pathology: Protective action of thyroid hormone.

Clinical evidence indicates that injury to the brain elicits systemic metabolic disturbances that contributes to the brain pathology. Since dietary fructose is metabolized in the liver, we explored mechanisms by which traumatic brain injury (TBI) and dietary fructose influence liver function and their possible repercussions to brain. Consumption of fructose contributed to the detrimental effects of TBI on liver operation, in terms of glucose and lipid metabolism, de novo lipogenesis, lipid peroxidation.

PTEN knockout using retrogradely transported AAVs restores locomotor abilities in both acute and chronic spinal cord injury.

Restoring function in chronic stages of spinal cord injury (SCI) has often been met with failure or reduced efficacy when regenerative strategies are delayed past the acute or sub-acute stages of injury. Restoring function in the chronically injured spinal cord remains a critical challenge. We found that a single injection of retrogradely transported adeno-associated viruses (AAVrg) to knockout the phosphatase and tensin homolog protein (PTEN) in chronic SCI can effectively target both damaged and spared axons and restore locomotor functions in near-complete injury models.