ArticleExperimental neurology2021
Delayed dosing of minocycline plus N-acetylcysteine reduces neurodegeneration in distal brain regions and restores spatial memory after experimental traumatic brain injury.
Article in Experimental neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Synaptic Pathology in Traumatic Brain Injury and Therapeutic Insights.International journal of molecular sciences · 2025Review
- Unlocking therapeutic potential in traumatic brain injury: exploring microenvironmental targets, signaling pathways and translational hurdles.Inflammopharmacology · 2025Review
- Doxycycline: An essential tool for Alzheimer's disease.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Review
- Subregional differences in the hippocampal transcriptomic response after penetrating traumatic brain injury in rats.Frontiers in neurology · 2025Article
- Current state of neuroprotective therapy using antibiotics in human traumatic brain injury and animal models.BMC neuroscience · 2024Review
- N-Acetylcysteine and Probenecid Adjuvant Therapy for Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Treating Traumatic Brain Injury with Minocycline.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Scientific Rationale for the Treatment of Cognitive Deficits from Long COVID.Neurology international · 2023Review
- Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review.Journal of clinical medicine · 2023Review
- Minocycline alleviated scopolamine-induced amnesia by regulating antioxidant and cholinergic function.Heliyon · 2023Article
- A single closed head injury in male adult mice induces chronic, progressive white matter atrophy and increased phospho-tau expressing oligodendrocytes.Experimental neurology · 2023Article
- Better together? Treating traumatic brain injury with minocycline plus N-acetylcysteine.Neural regeneration research · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Multiple drugs to treat traumatic brain injury (TBI) have failed clinical trials. Most drugs lose efficacy as the time interval increases between injury and treatment onset. Insufficient therapeutic time window is a major reason underlying failure in clinical trials. Few drugs have been developed with therapeutic time windows sufficiently long enough to treat TBI because little is known about which brain functions can be targeted if therapy is delayed hours to days after injury. We identified multiple injury parameters that are improved by first initiating treatment with the drug combination minocycline (MINO) plus N-acetylcysteine (NAC) at 72 h after injury (MN72) in a mouse closed head injury (CHI) experimental TBI model. CHI produces spatial memory deficits resulting in impaired performance on Barnes maze, hippocampal neuronal loss, and bilateral damage to hippocampal neurons, dendrites, spines and synapses. MN72 treatment restores Barnes maze acquisition and retention, protects against hippocampal neuronal loss, limits damage to dendrites, spines and synapses, and accelerates recovery of microtubule associated protein 2 (MAP2) expression, a key protein in maintaining proper dendritic architecture and synapse density. These data show that in addition to the structural integrity of the dendritic arbor, spine and synapse density can be successfully targeted with drugs first dosed days after injury. Retention of substantial drug efficacy even when first dosed 72 h after injury makes MINO plus NAC a promising candidate to treat clinical TBI.
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Registered trials
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