Extracellular Vesicle–Derived miR-124 Resolves Radiation-Induced Brain Injury

Objective Sirtuin 3 (SIRT3) plays a vital role in regulating oxidative stress in tissue injury. The aim of this study was to evaluate the radioprotective effects of honokiol (HKL) in a zebrafish model of radiation-induced brain injury and in HT22 cells. Methods The levels of reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β) were evaluated in the zebrafish brain and HT22 cells. The expression levels of SIRT3 and cyclooxygenase-2 (COX-2) were measured using western blot assays and real-time polymerase chain reaction (RT-PCR). Results HKL treatment attenuated the levels of ROS, TNF-α, and IL-1β in both the in vivo and in vitro models of irradiation injury. Furthermore, HKL treatment increased the expression of SIRT3 and decreased the expression of COX-2. The radioprotective effects of HKL were achieved via SIRT3 activation. Conclusions HKL attenuated oxidative stress and pro-inflammatory responses in a SIRT3-dependent manner in radiation-induced brain injury.

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The Management of Radiation-Induced Brain Injury

Cancer Treatment and Research - Radiation Toxicity: A Practical Guide ◽

10.1007/0-387-25354-8_2 ◽

2008 ◽

pp. 7-22 ◽

Cited By ~ 24

Author(s):

Edward G. Shaw ◽

Mike E. Robbins

Keyword(s):

Brain Injury ◽

Radiation Induced

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Low serum 25‐hydroxyvitamin D3 levels and late delayed radiation‐induced brain injury in patients with nasopharyngeal carcinoma: A case–control study

Brain and Behavior ◽

10.1002/brb3.1892 ◽

2020 ◽

Vol 10 (12) ◽

Author(s):

Zhezhi Deng ◽

Minping Li ◽

Junjie Guo ◽

Dongxiao Zhou ◽

Xurui Huang ◽

...

Keyword(s):

Brain Injury ◽

Nasopharyngeal Carcinoma ◽

Case Control Study ◽

Case Control ◽

Radiation Induced ◽

Control Study ◽

Low Serum

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Micro Ribonucleic Acid Profiles of Traumatic Brain Injury Isolated From Plasma Extracellular Vesicles

Neurosurgery ◽

10.1093/neuros/nyz310_831 ◽

2019 ◽

Vol 66 (Supplement_1) ◽

Author(s):

Ross Puffer ◽

Luz Cumba-Garcia ◽

Benjamin T Himes ◽

David O Okonkwo ◽

Ian F Parney

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Extracellular Vesicles ◽

Rna Isolation ◽

Extracellular Vesicle ◽

Micro Rna ◽

Altered Consciousness ◽

Rna Sequences ◽

Altered Level ◽

Level Of Consciousness

Abstract INTRODUCTION Extracellular vesicles (EVs) are membrane-bound particles released by the majority of human cells, including cells within the central nervous system. They may represent a diagnostic or prognostic target obtainable in peripheral blood of neurotrauma patients. We have isolated micro RNA sequences contained within EVs of 15 patients with traumatic brain injury (TBI) and compared them to miRNA sequences from 5 healthy controls. METHODS Extracellular vesicles were isolated from 15 TBI subjects, including 6 mild TBI (Glasgow Coma Scale (GCS) 13-15), 3 moderate TBI (GCS 9-12), and 6 severe TBI (GCS 3-8), as well as 5 healthy control. EVs were analyzed using nanoparticle tracking analysis. Samples underwent RNA isolation and extraction, followed by miRNA sequencing and analysis. RESULTS TBI patients presenting with an altered level of consciousness (GCS = 14) had a significantly higher mean extracellular vesicle size compared to subjects with normal GCS (mean + /− sem = 108.3 nm + /− 7.7 nm vs 89.2 nm + /− 6.7 nm; P < .04). GFAP ELISA of the samples demonstrated significantly higher GFAP concentration in subjects with altered level of consciousness (GCS = 14) as compared to those with normal GCS (mean + /− sem GFAP concentration 2204.2 pg/mL + /− 1067.2 pg/mL vs. 207.8 pg/mL + /− 270.8 pg/mL, P = .05). We identified 9 miRNA sequences that were found in a significantly higher proportion in patients with altered consciousness compared to controls, as well as 2 miRNA sequences that were significantly downregulated in subjects with altered consciousness as compared to controls. CONCLUSION EVs may contain brain specific biomarkers that are released in greater quantities after TBI. These molecules can be isolated from plasma and sequenced. Further analysis will better elucidate the final pathways affected by these up and downregulated miRNA sequences. Analysis of EVs in subjects with TBI may allow for the identification of novel diagnostic and potentially prognostic biomarkers.

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