ArticleBrain, behavior, and immunity2019
Reducing age-dependent monocyte-derived macrophage activation contributes to the therapeutic efficacy of NADPH oxidase inhibition in spinal cord injury.
Article in Brain, behavior, and immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Regulating PPARG Reduces Lipid Accumulation in Microglia and Promotes Functional Recovery After Spinal Cord Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular pathology of acute spinal cord injury in middle-aged mice.Journal of neuroinflammation · 2025Article
- Redefining macrophage phenotypes after spinal cord injury: An open data approach.Experimental neurology · 2025Article
- Advancements in Antioxidant-Based Therapeutics for Spinal Cord Injury: A Critical Review of Strategies and Combination Approaches.Antioxidants (Basel, Switzerland) · 2024Review
- Facile construction of dual-response super-resolution probes for tracking organelles dynamics.Exploration (Beijing, China) · 2024Article
- Old age alters inflammation and autophagy signaling in the brain, leading to exacerbated neurological outcomes after spinal cord injury in male mice.Brain, behavior, and immunity · 2024Article
- Caffeic acid phenethyl ester inhibits neuro-inflammation and oxidative stress following spinal cord injury by mitigating mitochondrial dysfunction via the SIRT1/PGC1α/DRP1 signaling pathway.Journal of translational medicine · 2024Article
- Article
- Angiotensin Type 2 Receptor Pharmacological Agonist Relieves Neurocognitive Deficits via Reducing Neuroinflammation and Microglial Engulfment of Dendritic Spines.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Article
- Bioinformatics analysis of ferroptosis in spinal cord injury.Neural regeneration research · 2023Article
- Effects of NADPH Oxidase Isoform-2 (NOX2) Inhibition on Behavioral Responses and Neuroinflammation in a Mouse Model of Neuropathic Pain.Biomedicines · 2023Article
- Challenges in Translating Regenerative Therapies for Spinal Cord Injury.Topics in spinal cord injury rehabilitation · 2023Article
- Advanced Age and Neurotrauma Diminish Glutathione and Impair Antioxidant Defense after Spinal Cord Injury.Journal of neurotrauma · 2022Article
- Immunoglobulin G Is Increased in the Injured Spinal Cord in a Sex- and Age-Dependent Manner.Journal of neurotrauma · 2022Article
- Polyphenols Targeting Oxidative Stress in Spinal Cord Injury: Current Status and Future Vision.Oxidative medicine and cellular longevity · 2022Review
- Therapeutic targeting of microglia mediated oxidative stress after neurotrauma.Frontiers in medicine · 2022Review
- Improving translatability of spinal cord injury research by including age as a demographic variable.Frontiers in cellular neuroscience · 2022Review
- Acute inflammatory profiles differ with sex and age after spinal cord injury.Journal of neuroinflammation · 2021Article
- Mitochondria exert age-divergent effects on recovery from spinal cord injury.Experimental neurology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
objectiveThe average age at the time of spinal cord injury (SCI) has increased to 43 years old. Middle-aged mice (14 months old, MO) exhibit impaired recovery after SCI with age-dependent increases in reactive oxygen species (ROS) production through NADPH oxidase (NOX) along with pro-inflammatory macrophage activation. Despite these aging differences, clinical therapies are being examined in individuals regardless of age based upon preclinical data generated primarily using young animals (∼4 MO). Our objective is to test the extent to which age affects SCI treatment efficacy. Specifically, we hypothesize that the effectiveness of apocynin, a NOX inhibitor, is age-dependent in SCI.
methodsApocynin treatment (5 mg/kg) or vehicle was administered 1 and 6 h after moderate T9 contusion SCI (50kdyn IH) and then daily for 1 week to 4 and 14 MO mice. Locomotor and anatomical recovery was evaluated for 28 days. Monocyte-derived macrophage (MDM) and microglial activation and ROS production were evaluated at 3 and 28 days post-injury.
resultsApocynin improved functional and anatomical recovery in 14 but not 4 MO SCI mice. Apocynin-mediated recovery was coincident with significant reductions in MDM infiltration and MDM-ROS production in 14 MO SCI mice. Importantly, microglial activation was unaffected by treatment.
conclusionThese results indicate that apocynin exhibits age-dependent neuroprotective effects by blocking excessive neuroinflammation through NOX-mediated ROS production in MDMs. Further, these data identify age as a critical regulator for SCI treatment efficacy and indicate that pharmacologically reduced macrophage, but not microglia, activation and ROS production reverses age-associated neurological impairments.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.