Antioxidant thioether core-crosslinked nanoparticles prevent the bilateral spread of secondary injury to protect spatial learning and memory in a controlled cortical impact mouse model of traumatic brain injury

Tarudji, Aria W.; Gee, Connor C.; Romereim, Sarah M.; Convertine, Anthony J.; Kievit, Forrest M.

doi:10.1016/j.biomaterials.2021.120766

Cited by 30 publications

(16 citation statements)

References 76 publications

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“…3 E, during the learning phase, the average escape latency of the APP/PS1-GABA sEV group mice was significantly shorter than that of APP/PS1-Ctrl sEV group mice from Day 2 in quadrant I and III, while the average escape latency of the APP/PS1-Glutamate sEV group mice was significantly longer than that of the APP/PS1-Ctrl sEV group mice on Day 5 in quadrant II. Furthermore, for latency to escape, Kaplan–Meier survival analysis with the Mantel-Cox log-rank test was employed to account for the non-normal distribution of latencies resulting from the 60-s maximum trial duration according to the methods described previously [ 19 , 20 ]. We concluded that the APP/PS1-glutamate sEV group mice took significantly longer to escape on Days 3 and 5 of spatial acquisition than the control mice, as determined by the log-rank test (Fig.…”

Section: Resultsmentioning

confidence: 99%

Neurotransmitter-stimulated neuron-derived sEVs have opposite effects on amyloid β-induced neuronal damage

et al. 2021

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The ratio of excitatory to inhibitory neurotransmitters is essential for maintaining the firing patterns of neural networks, and is strictly regulated within individual neurons and brain regions. Excitatory to inhibitory (E/I) imbalance has been shown to participate in the progression of neurodegenerative diseases, including Alzheimer's disease (AD). Glutamate excitotoxicity and GABAergic neuron dysfunction appear to be key components of the neuronal cell death that takes place in AD. Since extracellular vesicles (EVs) are now explored as an important vehicle in transmitting signals between cells, we hypothesized that the function of neuron-derived small EVs (sEVs) might be regulated by the status of neurotransmitter balance and that sEVs might affect amyloid β (Aβ) toxicity on neurons. This study aimed to reveal the effects of sEVs from unbalanced neurotransmitter-stimulated neurons on Aβ-induced toxicity. We demonstrated the opposite effects of the two groups of sEVs isolated from neurons stimulated by glutamate or GABA on Aβ toxicity in vivo and in vitro. The sEVs released from GABA-treated neurons alleviated Aβ-induced damage, while those released from glutamate-treated neurons aggravated Aβ toxicity. Furthermore, we compared the microRNA (miRNA) composition of sEVs isolated from glutamate/GABA/PBS-treated neurons. Our results showed that glutamate and GABA oppositely regulated miR-132 levels in sEVs, resulting in the opposite destiny of recipient cells challenged with Aβ. Our results indicated that manipulating the function of sEVs by different neurotransmitters may reveal the mechanisms underlying the pathogenesis of AD and provide a promising strategy for AD treatment.

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Section: Resultsmentioning

confidence: 99%

Neurotransmitter-stimulated neuron-derived sEVs have opposite effects on amyloid β-induced neuronal damage

et al. 2021

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“…After TBI, excitatory amino acids such as glutamate release into the synapse which then overstimulates the N-methyl-D-aspartate (NMDA) receptor, which leads to Ca 2+ overload [ 180 , 181 ]. Ca 2+ overload and excitotoxicity induce reactive oxygen species (ROS) release [ 180 ], and excessive ROS causes oxidative stress and neuronal cell death [ 182 , 183 ]. Oxidative stress induces excessive free radicals, resulting in neuronal death, stimulating inflammation [ 184 ].…”

Section: The Role Of M 6 a Rna Modification In Tbi...mentioning

confidence: 99%

The Potential Role of m6A in the Regulation of TBI-Induced BGA Dysfunction

et al. 2022

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The brain–gut axis (BGA) is an important bidirectional communication pathway for the development, progress and interaction of many diseases between the brain and gut, but the mechanisms remain unclear, especially the post-transcriptional regulation of BGA after traumatic brain injury (TBI). RNA methylation is one of the most important modifications in post-transcriptional regulation. N6-methyladenosine (m6A), as the most abundant post-transcriptional modification of mRNA in eukaryotes, has recently been identified and characterized in both the brain and gut. The purpose of this review is to describe the pathophysiological changes in BGA after TBI, and then investigate the post-transcriptional bidirectional regulation mechanisms of TBI-induced BGA dysfunction. Here, we mainly focus on the characteristics of m6A RNA methylation in the post-TBI BGA, highlight the possible regulatory mechanisms of m6A modification in TBI-induced BGA dysfunction, and finally discuss the outcome of considering m6A as a therapeutic target to improve the recovery of the brain and gut dysfunction caused by TBI.

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Section: Figurementioning

confidence: 99%

The Nanotheranostic Researcher’s Guide for Use of Animal Models of Traumatic Brain Injury

McDonald

Gee

Kievit

2021

JNT

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Traumatic brain injury (TBI) is currently the leading cause of injury-related morbidity and mortality worldwide, with an estimated global cost of USD 400 billion annually. Both clinical and preclinical behavioral outcomes associated with TBI are heterogeneous in nature and influenced by the mechanism and frequency of injury. Previous literature has investigated this relationship through the development of animal models and behavioral tasks. However, recent advancements in these methods may provide insight into the translation of therapeutics into a clinical setting. In this review, we characterize various animal models and behavioral tasks to provide guidelines for evaluating the therapeutic efficacy of treatment options in TBI. We provide a brief review into the systems utilized in TBI classification and provide comparisons to the animal models that have been developed. In addition, we discuss the role of behavioral tasks in evaluating outcomes associated with TBI. Our goal is to provide those in the nanotheranostic field a guide for selecting an adequate TBI animal model and behavioral task for assessment of outcomes to increase research in this field.

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Antioxidant thioether core-crosslinked nanoparticles prevent the bilateral spread of secondary injury to protect spatial learning and memory in a controlled cortical impact mouse model of traumatic brain injury

Cited by 30 publications

References 76 publications

Neurotransmitter-stimulated neuron-derived sEVs have opposite effects on amyloid β-induced neuronal damage

Neurotransmitter-stimulated neuron-derived sEVs have opposite effects on amyloid β-induced neuronal damage

The Potential Role of m6A in the Regulation of TBI-Induced BGA Dysfunction

The Nanotheranostic Researcher’s Guide for Use of Animal Models of Traumatic Brain Injury

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