Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice

Luo, Chengliang; Li, B.-X.; Li, Q.-Q.; Chen, X.-P.; Sun, Yijian; Bao, Haijun; Dai, Ding-Kun; Shen, Yiwen; Xu, Hongfei; Ni, Haibo; Wan, Lihong; Qin, Zheng; Tao, Liyuan; Zhao, Zi‐Ai

doi:10.1016/j.neuroscience.2011.03.021

Cited by 181 publications

(148 citation statements)

References 46 publications

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“…[9][10][11][12][13][14]26,27 The first study investigating the association between autophagy and TBI was conducted by Diskin and colleagues. 11 In that study, it was demonstrated that Beclin-1 level dramatically increased near the site of injury in the closed-head injury model in mice.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas it is doubtless that autophagy increases after experimental TBI, however, several studies have concluded that the increased autophagy may contribute to the overall neuropathology and functional outcome deficits. 10,13,14 Whereas many studies have focused on the modulation of autophagy by apoptotic-signaling pathways, it is also clear that autophagy can regulate apoptosis. 4 In the present study, we have found that, post-TBI, moderate hypothermia could increase expression of autophagy and attenuate hippocampal cell death, which may suggest that the autophagy pathway may play an important role in the neuroprotective function of moderate hypothermia.…”

Section: Discussionmentioning

confidence: 99%

“…4 Recently, a series of studies has reported the increase of autophagy in subarachnoid hemorrhage, intracerebral hemorrhage, hypoxia-ischemia, neurodegenerative disease, and TBI. [5][6][7][8][9][10] However, the function of autophagy in TBI remains controversial. Some studies have proposed that activation of the autophagy pathway serves as a protective mechanism for maintaining cellular homeostasis post-TBI whereas other studies suggested that inhibition of the autophagy pathway may attenuate traumatic damage and functional outcome deficits.…”

Section: Introductionmentioning

confidence: 99%

“…Some studies have proposed that activation of the autophagy pathway serves as a protective mechanism for maintaining cellular homeostasis post-TBI whereas other studies suggested that inhibition of the autophagy pathway may attenuate traumatic damage and functional outcome deficits. [9][10][11][12][13][14] Several clinical and experimental studies have shown the neuroprotective effects of mild-to-moderate hypothermia, including inhibition of neurological injury, reduction of infarct size, and improvement of neurological outcome. [15][16][17][18] In our previous studies, we found that post-traumatic moderate hypothermia significantly attenuated cell death within the hippocampus after fluid percussion TBI.…”

Section: Introductionmentioning

confidence: 99%

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Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

Jin

Lin

Feng

et al. 2015

Journal of Neurotrauma

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Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI) followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were randomly divided into four groups: sham injury with normothermia group (37°C); sham injury with hypothermia group (32°C); TBI with normothermia group (TNG; 37°C); and TBI with hypothermia group (THG; 32°C). Injury was induced by a fluid percussion TBI device. Moderate hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 h. All rats were killed at 24 h after fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; terminal deoxynucleoitidyl transferasemediated nick end labeling staining was used to determine cell death in ipsilateral hippocampus. Immunohistochemistry and western blotting of microtubule-associated protein light chain 3 (LC3), Beclin-1, as well as transmission electron microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell death index was 27.90 -2.36% in TNG and 14.90 -1.52% in THG. Expression level of LC3 and Beclin-1 were significantly increased after TBI and were further up-regulated after post-TBI hypothermia. Further, ultrastructural observations showed that there was a marked increase of autophagosomes and autolysosomes in ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that moderate hypothermia significantly attenuated cell death and increased autophagy in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy pathway may participate in the neuroprotective effect of post-TBI hypothermia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

Jin

Lin

Feng

et al. 2015

Journal of Neurotrauma

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“…In penumbral regions where cells undergo delayed neurodegeneration, other mechanisms can dominate, including apoptosis, which is a programmed cell death cascade regulated by effector proteins and caspase protease activation [9,10], and autophagy, which is the lysosomal degradation of components within the cell [11][12][13]. These pathways are often mediated by a specific sequence of intracellular protein activation and have been heavily studied in the context of physiological cell function and also in trauma.…”

Section: Regulation Of Cell Deathmentioning

confidence: 99%

Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury

2012

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Traumatic brain injury (TBI) initiates a complex cascade of secondary neurodegenerative mechanisms contributing to cell dysfunction and necrotic and apoptotic cell death. The injured brain responds by activating endogenous reparative processes to counter the neurodegeneration or remodel the brain to enhance functional recovery. A vast array of genetically altered mice provide a unique opportunity to target single genes or proteins to better understand their role in cell death and endogenous repair after TBI. Among the earliest targets for transgenic and knockout studies in TBI have been programmed cell death mediators, such as the Bcl-2 family of proteins, caspases, and caspaseindependent pathways. In addition, the role of cell cycle regulatory elements in the posttraumatic cell death pathway has been explored in mouse models. As interest grows in neuroplasticity in TBI, the use of transgenic and knockout mice in studies focused on gliogenesis, neurogenesis, and the balance of growth-promoting and growth-inhibiting molecules has increased in recent years. With proper consideration of potential effects of constitutive gene alteration, traditional transgenic and knockout models can provide valuable insights into TBI pathobiology. Through increasing sophistication of conditional and cell-type specific genetic manipulations, TBI studies in genetically altered mice will be increasingly useful for identification and validation of novel therapeutic targets.

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Modulation of autophagy in traumatic brain injury

Zeng

Zhang

Jiang

et al. 2019

Journal Cellular Physiology

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Traumatic brain injury (TBI) is defined as a traumatically induced structural injury or physiological disruption of brain function as a result of external forces, leading to adult disability and death. A growing body of evidence reveals that alterations in autophagy-related proteins exist extensively in both experimentally and clinically after TBI. Of note, the autophagy pathway plays an essential role in pathophysiological processes, such as oxidative stress, inflammatory response, and apoptosis, thus contributing to neurological properties of TBI. With this in mind, this review summarizes a comprehensive overview on the beneficial and detrimental effects of autophagy in pathophysiological conditions and how these activities are linked to the pathogenesis of TBI. Moreover, the relationship between oxidative stress, inflammation, apoptosis, and autophagy occur TBI. Ultimately, multiple compounds and various drugs targeting the autophagy pathway are well described in TBI. Therefore, autophagy flux represents a potential clinical therapeutic value for the treatment of TBI and its complications.

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Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice

Cited by 181 publications

References 46 publications

Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

Genetic Manipulation of Cell Death and Neuroplasticity Pathways in Traumatic Brain Injury

Modulation of autophagy in traumatic brain injury

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