Impaired autophagic flux is associated with the severity of trauma and the role of A2AR in brain cells after traumatic brain injury

Zeng, Xujia; Li, Ping; Ning, Yuping; Zhao, Yan; Peng, Yan; Yang, Nan; Zhao, Zi‐Ai; Chen, Jiang‐Fan; Zhou, Yuan‐Guo

doi:10.1038/s41419-018-0316-4

Cited by 49 publications

(46 citation statements)

References 51 publications

(40 reference statements)

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“…Therefore, yellow dots (merged red and green dots) represent autophagosomes, while red dots represent autophagolysosomes. If autophagy is activated and autophagic flux is normal, red dots will dominate over yellow dots; if autophagic flux is impaired, more yellow dots than red dots will be observed 50 , 51 .…”

Section: Methodsmentioning

confidence: 99%

Therapeutic effects of rapamycin and surgical decompression in a rabbit spinal cord injury model

et al. 2020

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Surgical decompression after spinal cord injury (SCI) is a conventional treatment. Although it has been proven to have clinical effects, there are certain limitations, such as the surgical conditions that must be met and the invasive nature of the treatment. Therefore, there is an urgent need to develop a simple and maneuverable therapy for the emergency treatment of patients with SCI before surgery. Rapamycin (RAPA) has been reported to have potential as a therapeutic agent for SCI. In this study, we observed the therapeutic effects of rapamycin and surgical decompression, in combination or separately, on the histopathology in rabbits with SCI. After combination therapy, intramedullary pressure (IMP) decreased significantly, autophagic flux increased, and apoptosis and demyelination were significantly reduced. Compared with RAPA/surgical decompression alone, the combination therapy had a significantly better effect. In addition, we evaluated the effects of mechanical pressure on autophagy after SCI by assessing changes in autophagic initiation, degradation, and flux. Increased IMP after SCI inhibited autophagic degradation and impaired autophagic flux. Decompression improved autophagic flux after SCI. Our findings provide novel evidence of a promising strategy for the treatment of SCI in the future. The combination therapy may effectively improve emergency treatment after SCI and promote the therapeutic effect of decompression. This study also contributes to a better understanding of the effects of mechanical pressure on autophagy after neurotrauma.

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Section: Methodsmentioning

confidence: 99%

Therapeutic effects of rapamycin and surgical decompression in a rabbit spinal cord injury model

et al. 2020

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“…How NIX-related mitophagy exerts its effect at later times following TBI also needs to be understood, as does NIX-mediated apoptosis. It is reported that autophagy functions differently with various degrees of damage 51 . Therefore, the effects of autophagy or mitophagy in other forms of TBI-induced damage are likewise ambiguous.…”

Section: Discussionmentioning

confidence: 99%

Potential Roles of NIX/BNIP3L Pathway in Rat Traumatic Brain Injury

Qin

et al. 2019

Cell Transplant

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NIX/BNIP3L is known as a proapoptotic protein that is also related to mitophagy. Previous reports have shown that NIX could be involved in neuronal apoptosis after intracerebral hemorrhage, but it also plays a protective role in mitophagy in ischemic brain injury. How NIX works in traumatic brain injury (TBI) is unclear. Thus, this study was designed to observe the expression of NIX and perform a preliminary exploration of the possible effects of NIX in a rat TBI model. The results showed that NIX expression decreased after damage, and colocalized with neuronal cells in cortical areas. Moreover, when we induced upregulation of NIX, autophagy was increased, while neuronal apoptosis and brain water content decreased along with neurological deficits. These findings remind us that NIX probably plays a neuroprotective role in TBI through autophagy and apoptosis pathways.

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“…Through this pathway, the contents are degraded following fusion with the lysosomal compartment [28]. However, abnormalities in any of the above stages may lead to autophagic flux disorders and further disturb the physiological activity of the body [135,136].…”

Section: The Involvement Of Autophagy Dysfunction In Organelle Impairmentioning

confidence: 99%

“…Normal autophagy can remove abnormally synthesized proteins in cells and digest damaged and redundant organelles, which is beneficial for intracellular homeostasis. However, abnormalities in any of the above stages may lead to autophagic flux disorders and further disturb the physiological activity of the body [ 135 , 136 ].…”

Section: Introductionmentioning

confidence: 99%

Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine

Feng

Zhang

et al. 2020

Part Fibre Toxicol

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Background Widespread biomedical applications of nanomaterials (NMs) bring about increased human exposure risk due to their unique physicochemical properties. Autophagy, which is of great importance for regulating the physiological or pathological activities of the body, has been reported to play a key role in NM-driven biological effects both in vivo and in vitro. The coexisting hazard and health benefits of NM-mediated autophagy in biomedicine are nonnegligible and require our particular concerns. Main body We collected research on the toxic effects related to NM-mediated autophagy both in vivo and in vitro. Generally, NMs can be delivered into animal models through different administration routes, or internalized by cells through different uptake pathways, exerting varying degrees of damage in tissues, organs, cells, and organelles, eventually being deposited in or excreted from the body. In addition, other biological effects of NMs, such as oxidative stress, inflammation, necroptosis, pyroptosis, and ferroptosis, have been associated with autophagy and cooperate to regulate body activities. We therefore highlight that NM-mediated autophagy serves as a double-edged sword, which could be utilized in the treatment of certain diseases related to autophagy dysfunction, such as cancer, neurodegenerative disease, and cardiovascular disease. Challenges and suggestions for further investigations of NM-mediated autophagy are proposed with the purpose to improve their biosafety evaluation and facilitate their wide application. Databases such as PubMed and Web of Science were utilized to search for relevant literature, which included all published, Epub ahead of print, in-process, and non-indexed citations. Conclusion In this review, we focus on the dual effect of NM-mediated autophagy in the biomedical field. It has become a trend to use the benefits of NM-mediated autophagy to treat clinical diseases such as cancer and neurodegenerative diseases. Understanding the regulatory mechanism of NM-mediated autophagy in biomedicine is also helpful for reducing the toxic effects of NMs as much as possible.

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Impaired autophagic flux is associated with the severity of trauma and the role of A2AR in brain cells after traumatic brain injury

Cited by 49 publications

References 51 publications

Therapeutic effects of rapamycin and surgical decompression in a rabbit spinal cord injury model

Therapeutic effects of rapamycin and surgical decompression in a rabbit spinal cord injury model

Potential Roles of NIX/BNIP3L Pathway in Rat Traumatic Brain Injury

Nanomaterial-mediated autophagy: coexisting hazard and health benefits in biomedicine

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