Oxidative Stress and Inflammatory Response in Early Stage of Diffuse Axonal Injury in Rats

Diffuse axonal injury (DAI) is the most severe pathological feature of traumatic brain injury. However, how primary axonal injury is induced by mechanical stress and whether it could be mitigated remain unknown, largely due to the resolution limits of medical imaging approaches. Here we established an Axon-on-a-Chip (AoC) model for mimicking DAI and investigating its early cellular responses. By integrating computational fluid dynamics and microfluidic techniques, DAI was observed for the first time during mechanical stress, and a clear correlation between stress intensity and severity of DAI was elucidated. This AoC was further used to investigate the dynamic intracellular changes occurring simultaneously with stress, and identified delayed local Ca2+ surges escorted rapid disruption of periodic axonal cytoskeleton during the early stage of DAI. Compatible with high-resolution live-microscopy, this model hereby provides a versatile system to identify early mechanisms underlying DAI, offering a platform for screening effective treatments to alleviate brain injuries.

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Advanced oxidation protein products and inflammatory markers in liver cirrhosis: a comparison between alcohol-related and HCV-related cirrhosis.

Acta Biochimica Polonica ◽

10.18388/abp.2011_2286 ◽

2011 ◽

Vol 58 (1) ◽

Cited By ~ 15

Author(s):

Jolanta Zuwała-Jagiełło ◽

Monika Pazgan-Simon ◽

Krzysztof Simon ◽

Maria Warwas

Keyword(s):

Oxidative Stress ◽

Liver Cirrhosis ◽

Inflammatory Response ◽

Chronic Inflammation ◽

Inflammatory Markers ◽

Antioxidant Defense ◽

Early Stage ◽

Plasma Concentrations ◽

Advanced Oxidation ◽

Advanced Oxidation Protein Products

Advanced oxidation protein products (AOPPs) are protein markers of oxidative stress with pro-inflammatory properties that accumulated in liver cirrhosis. In the present study, we investigated the association between chronic inflammatory response triggered by AOPPs and the severity of liver disease as assessed by the Child-Pugh score. Plasma concentrations of AOPPs and inflammatory markers such as C-reactive protein, tumor necrosis factor-α, and interleukin-6 were measured in 41 patients with HCV-related cirrhosis, 43 patients with alcohol-related liver cirrhosis (ALC), and in 30 age and sex matched controls. In comparison with controls, AOPPs were increased in HCV-related compensated (Child-Pugh A) and decompensated (Child-Pugh B-C) cirrhosis and in alcohol-related compensated cirrhosis. AOPPs level positively correlated with Child-Pugh score in alcohol-related cirrhosis but not in HCV-related cirrhosis and the correlation with the indices of chronic inflammation was stronger in ALC. In turn, AOPPs in HCV-related cirrhosis was related to inflammation to a lesser extent, but a significant correlation with antioxidant defense could be noted. In summary, liver cirrhosis was associated with increased formation of AOPPs, which differed between alcohol-related and HCV-related cirrhosis with respect to the relationship between AOPPs and antioxidant defense, stage of liver cirrhosis, and inflammatory response. The significant correlation between AOPPs accumulation and indices of chronic inflammation, more specifically TNF-α, suggests that oxidative stress may be a mediator of chronic inflammatory state in the early stage of alcohol-related cirrhosis.

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Diffuse Axonal Injury: Clinical Prognostic Factors, Molecular Experimental Models and the Impact of the Trauma Related Oxidative Stress. An Extensive Review Concerning Milestones and Advances

International Journal of Molecular Sciences ◽

10.3390/ijms221910865 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10865

Author(s):

Mauro Palmieri ◽

Alessandro Frati ◽

Antonio Santoro ◽

Paola Frati ◽

Vittorio Fineschi ◽

...

Keyword(s):

Oxidative Stress ◽

Prognostic Factors ◽

Relevant Literature ◽

Axonal Injury ◽

Diffuse Axonal Injury ◽

Experimental Models ◽

Clinical Syndrome ◽

High Rate ◽

Peripheral Oxygen Saturation ◽

The Impact

Traumatic brain injury (TBI) is a condition burdened by an extremely high rate of morbidity and mortality and can result in an overall disability rate as high as 50% in affected individuals. Therefore, the importance of identifying clinical prognostic factors for diffuse axonal injury (DAI) in (TBI) is commonly recognized as critical. The aim of the present review paper is to evaluate the most recent contributions from the relevant literature in order to understand how each single prognostic factor determinates the severity of the clinical syndrome associated with DAI. The main clinical factors with an important impact on prognosis in case of DAI are glycemia, early GCS, the peripheral oxygen saturation, blood pressure, and time to recover consciousness. In addition, the severity of the lesion, classified on the ground of the cerebral anatomical structures involved after the trauma, has a strong correlation with survival after DAI. In conclusion, modern findings concerning the role of reactive oxygen species (ROS) and oxidative stress in DAI suggest that biomarkers such as GFAP, pNF-H, NF-L, microtubule associated protein tau, Aβ42, S-100β, NSE, AQP4, Drp-1, and NCX represent a possible critical target for future pharmaceutical treatments to prevent the damages caused by DAI.

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Diffuse Axonal Injury and Oxidative Stress: A Comprehensive Review

International Journal of Molecular Sciences ◽

10.3390/ijms18122600 ◽

2017 ◽

Vol 18 (12) ◽

pp. 2600 ◽

Cited By ~ 37

Author(s):

Alessandro Frati ◽

Daniela Cerretani ◽

Anna Fiaschi ◽

Paola Frati ◽

Vittorio Gatto ◽

...

Keyword(s):

Oxidative Stress ◽

Axonal Injury ◽

Diffuse Axonal Injury ◽

Comprehensive Review ◽

And Oxidative Stress

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Traumatic or diffuse axonal injury? Author's response

Neuropathology and Applied Neurobiology ◽

10.1046/j.1365-2990.2000.00266-5.x ◽

2000 ◽

Vol 26 (5) ◽

pp. 491-491 ◽

Cited By ~ 6

Author(s):

J. F. Geddes ◽

H. L. Whitwell ◽

D. I. Graham

Keyword(s):

Axonal Injury ◽

Diffuse Axonal Injury

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Radiological and cognitive characteristics of traumatic diffuse axonal injury

Aktuelle Neurologie ◽

10.1055/s-2006-953463 ◽

2006 ◽

Vol 33 (S 1) ◽

Author(s):

R. Scheid ◽

J.P. Schneider ◽

D. Ott ◽

K. Walther ◽

T. Guthke ◽

...

Keyword(s):

Axonal Injury ◽

Diffuse Axonal Injury ◽

Cognitive Characteristics

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MRI of the diffuse axonal injury

Journal of the Korean Radiological Society ◽

10.3348/jkrs.1992.28.1.61 ◽

1992 ◽

Vol 28 (1) ◽

pp. 61

Author(s):

Yang Gu Joo ◽

Young Hoon Woo ◽

Soo Jhi Suh

Keyword(s):

Axonal Injury ◽

Diffuse Axonal Injury

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Naringin Inhibits TNF-α Induced Oxidative Stress and Inflammatory Response in HUVECs via Nox4/NF-κ B and PI3K/Akt Pathways

Current Pharmaceutical Biotechnology ◽

10.2174/1389201015666141111114442 ◽

2014 ◽

Vol 15 (12) ◽

pp. 1173-1182 ◽

Cited By ~ 22

Author(s):

Wenshuang Li ◽

Changyuan Wang ◽

Jinyong Peng ◽

Jing Liang ◽

Yue Jin ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Response

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One Week of CDAHFD Induces Steatohepatitis and Mitochondrial Dysfunction with Oxidative Stress in Liver

International Journal of Molecular Sciences ◽

10.3390/ijms22115851 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5851

Author(s):

Takehito Sugasawa ◽

Seiko Ono ◽

Masato Yonamine ◽

Shin-ichiro Fujita ◽

Yuki Matsumoto ◽

...

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dysfunction ◽

High Fat Diet ◽

Early Stage ◽

Droplet Deposition ◽

Nonalcoholic Fatty Liver ◽

Stress Markers ◽

Mitochondrial Dna Copy Number ◽

Short Period ◽

And Oxidative Stress

The prevalence of nonalcoholic fatty liver disease (NAFLD) has been rapidly increasing worldwide. A choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) has been used to create a mouse model of nonalcoholic steatohepatitis (NASH). There are some reports on the effects on mice of being fed a CDAHFD for long periods of 1 to 3 months. However, the effect of this diet over a short period is unknown. Therefore, we examined the effect of 1-week CDAHFD feeding on the mouse liver. Feeding a CDAHFD diet for only 1-week induced lipid droplet deposition in the liver with increasing activity of liver-derived enzymes in the plasma. On the other hand, it did not induce fibrosis or cirrhosis. Additionally, it was demonstrated that CDAHFD significantly impaired mitochondrial respiration with severe oxidative stress to the liver, which is associated with a decreasing mitochondrial DNA copy number and complex proteins. In the gene expression analysis of the liver, inflammatory and oxidative stress markers were significantly increased by CDAHFD. These results demonstrated that 1 week of feeding CDAHFD to mice induces steatohepatitis with mitochondrial dysfunction and severe oxidative stress, without fibrosis, which can partially mimic the early stage of NASH in humans.

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