Inhibition of microRNA-711 limits angiopoietin-1 and Akt changes, tissue damage, and motor dysfunction after contusive spinal cord injury in mice

Sabirzhanov, Boris; Matyas, Jessica; Coll-Miró, Marina; Yu, Laina Lijia; Faden, Alan I.; Stoica, Bogdan A.; Wu, Junfang

doi:10.1038/s41419-019-2079-y

Cited by 28 publications

(17 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proteins from both perilesional cortex and ipsilateral hippocampus were extracted by RIPA buffer containing protease inhibitors and phosphatase inhibitor, then quantified by BCA assay. Twenty micro gram of proteins were loaded onto 4-20% SDS-PAGE gels (Cat# 4561096, Bio-Rad; Hercules, CA) as previously described (Sabirzhanov et al, 2019). Proteins were transferred onto nitrocellulose membranes and then blocked for 1 hr in 5% milk in 1× PBS containing 0.05% Tween 20 (PBS-T) at room temperature.…”

Section: Western Blottingmentioning

confidence: 99%

Proton extrusion during oxidative burst in microglia exacerbates pathological acidosis following traumatic brain injury

Ritzel

et al. 2020

Glia

Self Cite

View full text Add to dashboard Cite

Acidosis is among the least studied secondary injury mechanisms associated with neurotrauma. Acute decreases in brain pH correlate with poor long‐term outcome in patients with traumatic brain injury (TBI), however, the temporal dynamics and underlying mechanisms are unclear. As key drivers of neuroinflammation, we hypothesized that microglia directly regulate acidosis after TBI, and thereby, worsen neurological outcomes. Using a controlled cortical impact model in adult male mice we demonstrate that intracellular pH in microglia and extracellular pH surrounding the lesion site are significantly reduced for weeks after injury. Microglia proliferation and production of reactive oxygen species (ROS) were also increased during the first week, mirroring the increase in extracellular ROS levels seen around the lesion site. Microglia depletion by a colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, markedly decreased extracellular acidosis, ROS production, and inflammation in the brain after injury. Mechanistically, we identified that the voltage‐gated proton channel Hv1 promotes oxidative burst activity and acid extrusion in microglia. Compared to wildtype controls, microglia lacking Hv1 showed reduced ability to generate ROS and extrude protons. Importantly, Hv1‐deficient mice exhibited reduced pathological acidosis and inflammation after TBI, leading to long‐term neuroprotection and functional recovery. Our data therefore establish the microglial Hv1 proton channel as an important link that integrates inflammation and acidosis within the injury microenvironment during head injury.

show abstract

Section: Western Blottingmentioning

confidence: 99%

Proton extrusion during oxidative burst in microglia exacerbates pathological acidosis following traumatic brain injury

Ritzel

et al. 2020

Glia

Self Cite

View full text Add to dashboard Cite

show abstract

“…The loss of neurons and glial cells can be considered as one of the main causes of permanent functional dysfunction after SCI, in which various cell transplants need to be used to compensate the loss of neurons and glial cells, guide axonal growth, and treat the SCI (Sabirzhanov et al, 2019;Li et al, 2017). In the present study, high-purity BMSCs obtained in vitro were transplanted into the injured spinal cord after induction of neuron-like cells by edaravone.…”

Section: Discussionmentioning

confidence: 95%

“…Bone marrow mesenchymal stem cells (BMSCs) possess incomparable advantages over other stem cells (Flouzat-Lachaniette et al, 2016;Hernigon et al, 2015;Long et al, 2018). In animal studies, BMSCs have displayed many advantages in the treatment of SCI (Ramalho et al, 2018;Sabirzhanov et al, 2019;Wang et al, 2019). Therefore, exploration of BMSC transplantation for SCI associates with clinical significance and broad research prospects.…”

Section: Introductionmentioning

confidence: 99%

Effects of Edaravone on Functional Recovery of a Rat Model with Spinal Cord Injury Through Induced Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells

Liu

Zhou

et al. 2021

Cellular Reprogramming

View full text Add to dashboard Cite

Edaravone can induce differentiation of bone marrow mesenchymal stem cells (BMSCs) into neuron-like cells and replace lost cells by transplanting neuron-like cells to repair spinal cord injury (SCI). In this study, BMSCs were derived from the bone marrow of male Wistar rats (4 weeks old) through density gradient centrifugation (1.073 g/ mL), and the cell purity of BMSCs was up to 95%. The combined injection of basic fibroblast growth factor and edaravone was conducted to differentiate BMSCs into neuron-like cells. In this study, 120 male Wistar rats were used to establish the model of semitransverse SCI; on the seventh day, neuron-like cells were labeled by BrdU and then injected into the epicenter of the injury of rats. On the 14th day after cell transplantation, the biotin dextran amine (BDA) fluorescent agent was used to track the repair of nerve damage. At 7, 14, 21, and 30 days after SCI, the Basso, Beattie, and Bresnahan (BBB) locomotor scale method was used to measure the functional recovery of hind limbs in rats. Additionally, hematoxylin and eosin (H&E) staining, Nissl staining, immunohistochemistry, transmission electron microscopy (TEM), Western blotting, and Real-time quantitative reverse transcripion PCR (qRT-PCR) were used to observe the regeneration of nerve cells. In the edaravone+BMSC group, behavioral analysis of locomotor function showed that functional recovery was significantly enhanced after transplantation of the cells, BrdU-positive cells could be observed scattered in the injured area and extended to both the head and tail, and the BDA tracer shows that the edaravone+BMSC group emits more fluorescent signals. Additionally, H&E staining, Nissl staining, and immunohistochemistry revealed that the space of spinal cord tissue was attenuated and the neurons were increased. Western blotting and qRT-PCR showed that the expression levels of neuron-specific enolase (NSE), Nestin, and neurofilament 200 (NF) were increased, while the expression of glial fibrillary acidic protein (GFAP) was decreased. TEM showed that cytoplasmic edema was reduced, mitochondrial vacuoles were attenuated, and nuclear chromatin concentration was declined after transplantation of neuron-like cells. Moreover, with the extension of time of edaravone+BMSC transplantation, the structures of mitochondria and endoplasmic reticulum tended to be normal. In summary, the induced differentiation of BMSC transplantation can significantly promote the functional repair of SCI.

show abstract

“…For example, Feng et al demonstrated that miR-204 was downregulated in the serum from SCI patients, and miR-204 overexpression promoted SCI recovery through inhibiting inflammatory response in SCI mice ( Feng et al, 2019 ). Boris Sabirzhanov et al showed that inhibition of miR-711 limited tissue damage and motor dysfunction after contusive SCI in mice ( Sabirzhanov et al, 2019 ). Wan et al revealed that miR-129-5p alleviated spinal cord injury in mice via suppressing the apoptosis and inflammatory response through HMGB1/TLR4/NF-kappaB pathway ( Wan et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Catalpol Protects Against Spinal Cord Injury in Mice Through Regulating MicroRNA-142-Mediated HMGB1/TLR4/NF-κB Signaling Pathway

Xia

Wang

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Spinal cord injury (SCI) is a devastating condition that leads to paralysis, disability and even death in severe cases. Inflammation, apoptosis and oxidative stress in neurons are key pathogenic processes in SCI. Catalpol (CTP), an iridoid glycoside extracted from Rehmannia glutinosa, has many pharmacological activities, such as anti-inflammatory, anti-oxidative and anti-apoptotic properties.Purpose: Here, we investigated whether CTP could exert neuroprotective effects against SCI, and explored the underlying mechanism involved.Methods: SCI was induced by a weight-drop device and treated with CTP (10 mg and 60 mg/kg). Then the locomotor function of SCI mice was evaluated by the BBB scores, spinal cord edema was measured by the wet/dry weight method, oxidative stress markers and inflammatory factors were detected by commercial kits and neuronal death was measured by TUNEL staining. Moreover, the microRNA expression profile in spinal cords from mice following SCI was analyzed using miRNA microarray. In addition, reactive oxygen species (ROS) generation, inflammatory response and cell apoptosis were detected in murine microglia BV2 cells under oxygen-glucose deprivation (OGD) and CTPtreatment.Results: Our data showed that CTP treatment could improve the functional recovery, as well as suppress the apoptosis, alleviate inflammatory and oxidative response in SCI mice. In addition, CTP was found to be up-regulated miR-142 and the protective effects of CTP on apoptosis, inflammatory and oxidative response may relate to its regulation of HMGB1/TLR4/NF-κB pathway through miR-142.Conclusion: Our findings suggest that CTP may protect the spinal cord from SCI by suppression of apoptosis, oxidative stress and inflammatory response via miR-142/HMGB1/TLR4/NF-κB pathway.

show abstract

Inhibition of microRNA-711 limits angiopoietin-1 and Akt changes, tissue damage, and motor dysfunction after contusive spinal cord injury in mice

Cited by 28 publications

References 77 publications

Proton extrusion during oxidative burst in microglia exacerbates pathological acidosis following traumatic brain injury

Proton extrusion during oxidative burst in microglia exacerbates pathological acidosis following traumatic brain injury

Effects of Edaravone on Functional Recovery of a Rat Model with Spinal Cord Injury Through Induced Differentiation of Bone Marrow Mesenchymal Stem Cells into Neuron-Like Cells

Catalpol Protects Against Spinal Cord Injury in Mice Through Regulating MicroRNA-142-Mediated HMGB1/TLR4/NF-κB Signaling Pathway

Contact Info

Product

Resources

About