P13BP, a calpain-2-mediated breakdown product of PTPN13, is a novel blood biomarker for Traumatic Brain Injury

2021 ◽  
Author(s):  
Yubin Wang ◽  
James Brazdzionis ◽  
Fanglong Dong ◽  
Tye Patchana ◽  
Hammad Ghanchi ◽  
...  
PLoS ONE ◽  
2009 ◽  
Vol 4 (2) ◽  
pp. e4491 ◽  
Author(s):  
Ann Miracle ◽  
Nancy D. Denslow ◽  
Kevin J. Kroll ◽  
Ming Cheng Liu ◽  
Kevin K. W. Wang

2017 ◽  
Vol 55 (1) ◽  
pp. 898-900
Author(s):  
Firas H. Kobeissy ◽  
Ming Cheng Liu ◽  
Zhihui Yang ◽  
Zhiqun Zhang ◽  
Wenrong Zheng ◽  
...  

2004 ◽  
Vol 21 (10) ◽  
pp. 1443-1456 ◽  
Author(s):  
N.C. Ringger ◽  
B.E. O'steen ◽  
J.G. Brabham ◽  
X. Silver ◽  
J. Pineda ◽  
...  

2020 ◽  
Vol 29 (5) ◽  
pp. 348-353
Author(s):  
Eiichi Suehiro ◽  
Yuichi Fujiyama ◽  
Miwa Kiyohira ◽  
Kouhei Haji ◽  
Michiyasu Suzuki

2021 ◽  
Vol 12 ◽  
Author(s):  
Sima Azizi ◽  
Daniel B. Hier ◽  
Blaine Allen ◽  
Tayo Obafemi-Ajayi ◽  
Gayla R. Olbricht ◽  
...  

Traumatic brain injury (TBI) imposes a significant economic and social burden. The diagnosis and prognosis of mild TBI, also called concussion, is challenging. Concussions are common among contact sport athletes. After a blow to the head, it is often difficult to determine who has had a concussion, who should be withheld from play, if a concussed athlete is ready to return to the field, and which concussed athlete will develop a post-concussion syndrome. Biomarkers can be detected in the cerebrospinal fluid and blood after traumatic brain injury and their levels may have prognostic value. Despite significant investigation, questions remain as to the trajectories of blood biomarker levels over time after mild TBI. Modeling the kinetic behavior of these biomarkers could be informative. We propose a one-compartment kinetic model for S100B, UCH-L1, NF-L, GFAP, and tau biomarker levels after mild TBI based on accepted pharmacokinetic models for oral drug absorption. We approximated model parameters using previously published studies. Since parameter estimates were approximate, we did uncertainty and sensitivity analyses. Using estimated kinetic parameters for each biomarker, we applied the model to an available post-concussion biomarker dataset of UCH-L1, GFAP, tau, and NF-L biomarkers levels. We have demonstrated the feasibility of modeling blood biomarker levels after mild TBI with a one compartment kinetic model. More work is needed to better establish model parameters and to understand the implications of the model for diagnostic use of these blood biomarkers for mild TBI.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Daniel B. Hier ◽  
Tayo Obafemi-Ajayi ◽  
Matthew S. Thimgan ◽  
Gayla R. Olbricht ◽  
Sima Azizi ◽  
...  

Abstract Background The use of blood biomarkers after mild traumatic brain injury (mTBI) has been widely studied. We have identified eight unresolved issues related to the use of five commonly investigated blood biomarkers: neurofilament light chain, ubiquitin carboxy-terminal hydrolase-L1, tau, S100B, and glial acidic fibrillary protein. We conducted a focused literature review of unresolved issues in three areas: mode of entry into and exit from the blood, kinetics of blood biomarkers in the blood, and predictive capacity of the blood biomarkers after mTBI. Findings Although a disruption of the blood brain barrier has been demonstrated in mild and severe traumatic brain injury, biomarkers can enter the blood through pathways that do not require a breach in this barrier. A definitive accounting for the pathways that biomarkers follow from the brain to the blood after mTBI has not been performed. Although preliminary investigations of blood biomarkers kinetics after TBI are available, our current knowledge is incomplete and definitive studies are needed. Optimal sampling times for biomarkers after mTBI have not been established. Kinetic models of blood biomarkers can be informative, but more precise estimates of kinetic parameters are needed. Confounding factors for blood biomarker levels have been identified, but corrections for these factors are not routinely made. Little evidence has emerged to date to suggest that blood biomarker levels correlate with clinical measures of mTBI severity. The significance of elevated biomarker levels thirty or more days following mTBI is uncertain. Blood biomarkers have shown a modest but not definitive ability to distinguish concussed from non-concussed subjects, to detect sub-concussive hits to the head, and to predict recovery from mTBI. Blood biomarkers have performed best at distinguishing CT scan positive from CT scan negative subjects after mTBI.


2008 ◽  
Vol 25 (9) ◽  
pp. 1079-1085 ◽  
Author(s):  
Kevin J. Anderson ◽  
Stephen W. Scheff ◽  
Kelly M. Miller ◽  
Kelly N. Roberts ◽  
Lesley K. Gilmer ◽  
...  

2006 ◽  
Vol 394 (3) ◽  
pp. 715-725 ◽  
Author(s):  
Ming Cheng Liu ◽  
Veronica Akle ◽  
Wenrong Zheng ◽  
Jitendra R. Dave ◽  
Frank C. Tortella ◽  
...  

A major theme of TBI (traumatic brain injury) pathology is the over-activation of multiple proteases. We have previously shown that calpain-1 and -2, and caspase-3 simultaneously produced αII-spectrin BDPs (breakdown products) following TBI. In the present study, we attempted to identify a comprehensive set of protease substrates (degradome) for calpains and caspase-3. We further hypothesized that the TBI differential proteome is likely to overlap significantly with the calpain- and caspase-3-degradomes. Using a novel HTPI (high throughput immunoblotting) approach and 1000 monoclonal antibodies (PowerBlot™), we compared rat hippocampal lysates from 4 treatment groups: (i) naïve, (ii) TBI (48 h after controlled cortical impact), (iii) in vitro calpain-2 digestion and (iv) in vitro caspase-3 digestion. In total, we identified 54 and 38 proteins that were vulnerable to calpain-2 and caspase-3 proteolysis respectively. In addition, the expression of 48 proteins was down-regulated following TBI, whereas that of only 9 was up-regulated. Among the proteins down-regulated in TBI, 42 of them overlapped with the calpain-2 and/or caspase-3 degradomes, suggesting that they might be proteolytic targets after TBI. We further confirmed several novel TBI-linked proteolytic substrates, including βII-spectrin, striatin, synaptotagmin-1, synaptojanin-1 and NSF (N-ethylmaleimide-sensitive fusion protein) by traditional immunoblotting. In summary, we demonstrated that HTPI is a novel and powerful method for studying proteolytic pathways in vivo and in vitro.


2017 ◽  
Vol 34 (23) ◽  
pp. 3245-3248 ◽  
Author(s):  
Kazutaka Sugimoto ◽  
Eiichi Suehiro ◽  
Mizuya Shinoyama ◽  
Hirokazu Sadahiro ◽  
Kouhei Haji ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document