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Ren C.,Capital Medical University | Ren C.,Xuanwu Banyan Biomarker Research and Assay Center | ZoItewicz S.,Banyan Biomarkers, Inc. | ZoItewicz S.,Xuanwu Banyan Biomarker Research and Assay Center | And 20 more authors.
Brain Research | Year: 2013

The two primary categories of stroke, ischemic and hemorrhagic, both have fundamentally different mechanisms and thus different treatment options. These two stroke categories were applied to rat models to identify potential biomarkers that can distinguish between them. Ischemic stroke was induced by middle cerebral artery occlusion (MCAO) without reperfusion while hemorrhagic stroke was induced by injecting collagenase IV into the striatum. Brain hemispheres and biofluids were collected at two time points: 3 and 6 h after stroke. Known molecules were tested on the rat samples via quantitative immunoblotting (injured brain, CSF) and Banyan's proprietary ELISA assays (CSF, serum). The injured brain quantitative analyses revealed that aII-spectrin breakdown products (SBDP150, SBDP145) were strongly increased after 6 h ischemia. In CSF, SBDP145 and ubiquitin C-terminal hydrolase-L1 (UCH-L1) levels were elevated after 6 h ischemic stroke detected by Western blot and ELISA. In serum UCH-L1 levels were increased after 3 and 6 h of ischemia detected by ELISA. However, levels of those proteins in hemorrhagic stroke remain normal. In summary, in both the brain and the biofluids, SBDPs andUCH- L1wereelevatedafterischemicbutnothemorrhagic stroke. These molecules behaved differently in the two stroke models and thus may be capable of being differentiated. © 2013 Elsevier B.V.

Ren C.,Capital Medical University | Ren C.,Xuanwu Banyan Biomarker Research and Assay Center | Guingab-Cagmat J.,Banyan Biomarkers, Inc. | Guingab-Cagmat J.,Xuanwu Banyan Biomarker Research and Assay Center | And 18 more authors.
Brain Research Bulletin | Year: 2014

Intracerebral hemorrhage (ICH) is a devastating form of stroke leading to a high rate of death and disability worldwide. Although it has been hypothesized that much of the IHC insult occurs in the subacute period mediated via a series of complex pathophysiological cascades, the molecular mechanisms involved in ICH have not been systematically characterized. Among the best approaches to understand the underlying mechanisms of injury and recovery, protein dynamics assessment via proteomics/systems biology platforms represent one of the cardinal techniques optimized for mechanisms investigation and biomarker identification. A proteomics approach may provide a biomarker focused framework from which to identify candidate biomarkers of pathophysiological processes involved in brain injury after stroke. In this work, a neuroproteomic approach (LC-MS/MS) was applied to investigate altered expression of proteins that are induced in brain tissue 3. h after injury in a rat model of ICH. Data from sham and focal ischemic models were also obtained and used for comparison. Based on the differentially expressed protein profile, systems biology analysis was conducted to identify associated cellular processes and related interaction maps. After LC-MS/MS analysis of the 3. h brain lysates, 86 proteins were differentially expressed between hemorrhagic and sham tissues. Furthermore, 38 proteins were differentially expressed between ischemic and sham tissues. On the level of global pathway analysis, hemorrhagic stroke proteins were shown to be involved in autophagy, ischemia, necrosis, apoptosis, calpain activation, and cytokine secretion. Moreover, ischemic stroke proteins were related to cell death, ischemia, inflammation, oxidative stress, caspase activation and apoptotic injury. In conclusion, the proteomic responses identified in this study provide key information about target proteins involved in specific pathological pathways. © 2014.

Mouhieddine T.H.,American University of Beirut | Itani M.M.,University of Nicosia | Nokkari A.,American University of Beirut | Ren C.,Capital Medical University | And 6 more authors.
Current Neurology and Neuroscience Reports | Year: 2015

Stroke is the second leading cause of death worldwide and a major cause of long-term severe disability representing a global health burden and one of the highly researched medical conditions. Nanostructured material synthesis and engineering have been recently developed and have been largely integrated into many fields including medicine. Recent studies have shown that nanoparticles might be a valuable tool in stroke. Different types, shapes, and sizes of nanoparticles have been used for molecular/biomarker profiling and imaging to help in early diagnosis and prevention of stroke and for drug/RNA delivery for improved treatment and neuroprotection. However, these promising applications have limitations, including cytotoxicity, which hindered their adoption into clinical use. Future research is warranted to fully develop and effectively and safely translate nanoparticles for stroke diagnosis and treatment into the clinic. This work will discuss the emerging role of nanotheragnostics in stroke diagnosis and treatment applications. © 2014, Springer Science+Business Media New York.

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