Ahmed Moghieb

Acute Diagnostic Biomarkers for Spinal Cord Injury: Review of the Literature and Preliminary Research Report

OBJECTIVE Many efforts have been made to create new diagnostic technologies for use in the diagnosis of central nervous system injury. However, there is still no consensus for the use of biomarkers in clinical acute spinal cord injury (SCI). The aims of this review are (1) to evaluate the current status of neurochemical biomarkers and (2) to discuss their potential acute diagnostic role in SCI by reviewing the literature. METHODS PubMed (http://www.ncbi.nlm.nih.gov/pubmed) was searched up to 2012 to identify publications concerning diagnostic biomarkers in SCI. To support more knowledge, we also checked secondary references in the primarily retrieved literature. RESULTS Neurofilaments, cleaved-Tau, microtubule-associated protein 2, myelin basic protein, neuron-specific enolase, S100β, and glial fibrillary acidic protein were identified as structural protein biomarkers in SCI by this review process. We could not find reports relating ubiquitin C-terminal hydrolase-L1 and α-II spectrin breakdown products, which are widely researched in other central nervous system injuries. Therefore, we present our preliminary data relating to these two biomarkers. Some of biomarkers showed promising results for SCI diagnosis and outcome prediction; however, there were unresolved issues relating to accuracy and their accessibility. CONCLUSION Currently, there still are not many reports focused on diagnostic biomarkers in SCI. This fact warranted the need for greater efforts to innovate sensitive and reliable biomarkers for SCI.

Differential Neuroproteomic and Systems Biology Analysis of Spinal Cord Injury

Acute spinal cord injury (SCI) is a devastating condition with many consequences and no known effective treatment. Although it is quite easy to diagnose traumatic SCI, the assessment of injury severity and projection of disease progression or recovery are often challenging, as no consensus biomarkers have been clearly identified. Here rats were subjected to experimental moderate or severe thoracic SCI. At 24h and 7d postinjury, spinal cord segment caudal to injury center versus sham samples was harvested and subjected to differential proteomic analysis. Cationic/anionic-exchange chromatography, followed by 1D polyacrylamide gel electrophoresis, was used to reduce protein complexity. A reverse phase liquid chromatography-tandem mass spectrometry proteomic platform was then utilized to identify proteome changes associated with SCI. Twenty-two and 22 proteins were up-regulated at 24 h and 7 day after SCI, respectively; whereas 19 and 16 proteins are down-regulated at 24 h and 7 day after SCI, respectively, when compared with sham control. A subset of 12 proteins were identified as candidate SCI biomarkers - TF (Transferrin), FASN (Fatty acid synthase), NME1 (Nucleoside diphosphate kinase 1), STMN1 (Stathmin 1), EEF2 (Eukaryotic translation elongation factor 2), CTSD (Cathepsin D), ANXA1 (Annexin A1), ANXA2 (Annexin A2), PGM1 (Phosphoglucomutase 1), PEA15 (Phosphoprotein enriched in astrocytes 15), GOT2 (Glutamic-oxaloacetic transaminase 2), and TPI-1 (Triosephosphate isomerase 1), data are available via ProteomeXchange with identifier PXD003473. In addition, Transferrin, Cathepsin D, and TPI-1 and PEA15 were further verified in rat spinal cord tissue and/or CSF samples after SCI and in human CSF samples from moderate/severe SCI patients. Lastly, a systems biology approach was utilized to determine the critical biochemical pathways and interactome in the pathogenesis of SCI. Thus, SCI candidate biomarkers identified can be used to correlate with disease progression or to identify potential SCI therapeutic targets.

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures “biomarkers” can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Neuroproteomics and systems biology approach to identify temporal biomarker changes post experimental traumatic brain injury in rats

Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics–systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal–global proteome changes after acute (1 day) and for the first time, subacute (7 days), post-injury time frame using the established cation–anion exchange chromatography-1D SDS gel electrophoresis LC–MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day) and subacute (7 days) periods post-TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7 days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is among the first to assess temporal neuroproteome changes in the CCI model. Data presented here unveil potential neural biomarkers and therapeutic targets that could be used for diagnosis, for treatment and, most importantly, for temporal prognostic assessment following brain injury. Of interest, this work relies on in silico bioinformatics approach to draw its conclusion; further work is conducted for functional studies to validate and confirm the omics data obtained.

The Application of Proteomics to Traumatic Brain and Spinal Cord Injuries

Traumatic brain injury (TBI) and traumatic spinal cord injury (SCI), collectively termed neurotrauma, are two parallel neurological conditions that can cause long-lasting neurological impairment and other comorbidities in patients, while at the same time, can create a high burden to society. To date, there are still no FDA-approved therapeutic interventions for either TBI or SCI. Recent advances in proteomic technologies, including tandem mass spectrometry, as well as imaging mass spectrometry, have enabled new approaches to study the differential proteome in TBI and SCI with the use of either animal disease models and/or biosamples from clinical observational studies. Thus, the applications of state-of-the-art proteomic method hold promises in shedding light on identifying clinically useful neurotrauma “biomarkers” and/or in identifying distinct and, otherwise, unobvious systems pathways or “key drivers” that can be further exploited as new therapeutic intervention targets.

Electrochemical Oxidation of Ethanol Using Heterobimetallic Complexes as an Approach to DEFC Catalysts

Direct alcohol fuel cells are useful power sources for portable applications such as electronic devices and vehicles because of their ease in handling and their ability to feed the liquid fuel directly to the anode Fuel cells utilizing methanol as the power source have been studied extensively within the past decades, however, research currently is focused on the use of Direct Ethanol Fuel Cells (DEFCs). Ethanol is an attractive alternative to methanol because it is less toxic and can easily be produced in large quantities by fermentation of biomass. We have previously reported that a series of dppmbridged Ru/Pd, Ru/Pt, and Ru/Au heterobimetallic complexes are catalysts for the electrooxidation of methanol. In order to extend these studies, the related ethanol soluble complex 2 was synthesized and its ability to oxidize ethanol studied. Complex 2 was prepared in high yield by reacting the κ-dppm Ru compound 1 with (COD)PdCl2 at room temperature (Equation 1). Related Ru/Pd and Ru/Pd complexes have also been prepared for study as electrocatalysis for ethanol oxidation.

Correction to: Protein Biomarkers and Neuroproteomics Characterization of Microvesicles/Exosomes from Human Cerebrospinal Fluid Following Traumatic Brain Injury

The original version of this article unfortunately contained a typographical error on Author’s name “Firas Kobessiy”. This should be corrected as “Firas Kobeissy”.

Biomarkers for CNS Injury and Regeneration

Abstract Traumatic and ischemic central nerve system (CNS) injury is a significant biomedical problem. It includes traumatic brain injury, ischemic stroke and hemorrhagic stroke (or intracerebral hemorrhage), subarachnoid hemorrhage, and spinal cord injury. There exists an urgent need to develop and refine biological measures of acute injury and chronic recovery after CNS injury. Such measures, “biomarkers,” can assist clinicians in helping to define and refine the recovery process and in developing treatment paradigms for the acutely injured to reduce secondary injury processes. In this chapter, we reviewed recent biomarker studies in CNS injury during acute, subacute, and chronic phases. Multiple types of biomarkers involved in acute brain injury, neuroinflammation, neurodegeneration, and neuroregeneration are summarized. Furthermore, a systems biology-driven biomarkers integration for traumatic brain injury is generated to present the scenario and complexity pathways involved in brain injury.