title: Deciphering glycomics and neuroproteomic alterations in experimental traumatic brain injury: Comparative analysis of aspirin and clopidogrel treatment.
abstract: As populations age, the number of patients sustaining traumatic brain injury (TBI) and concomitantly receiving preinjury antiplatelet therapy such as aspirin (ASA) and clopidogrel (CLOP) is rising. These drugs have been linked with unfavorable clinical outcomes following TBI, where the exact mechanism(s) involved are still unknown. In this novel work, we aimed to identify and compare the altered proteome profile imposed by ASA and CLOP when administered alone or in combination, prior to experimental TBI. Furthermore, we assessed differential glycosylation PTM patterns following experimental controlled cortical impact model of TBI, ASA, CLOP, and ASA + CLOP. Ipsilateral cortical brain tissues were harvested 48 h postinjury and were analyzed using an advanced neuroproteomics LC-MS/MS platform to assess proteomic and glycoproteins alterations. Of interest, differential proteins pertaining to each group (22 in TBI, 41 in TBI + ASA, 44 in TBI + CLOP, and 34 in TBI + ASA + CLOP) were revealed. Advanced bioinformatics/systems biology and clustering analyses were performed to evaluate biological networks and protein interaction maps illustrating molecular pathways involved in the experimental conditions. Results have indicated that proteins involved in neuroprotective cellular pathways were upregulated in the ASA and CLOP groups when given separately. However, ASA + CLOP administration revealed enrichment in biological pathways relevant to inflammation and proinjury mechanisms. Moreover, results showed differential upregulation of glycoproteins levels in the sialylated N-glycans PTMs that can be implicated in pathological changes. Omics data obtained have provided molecular insights of the underlying mechanisms that can be translated into clinical bedside settings.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.|Faculty of Medicine, Beirut Arab University, Beirut, Lebanon.
authors.forename: Hussein
authors.initials: H
authors.lastname: Abou-Abbass
authors.affiliation: Faculty of Medicine, Beirut Arab University, Beirut, Lebanon.|Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Hisham
authors.initials: H
authors.lastname: Bahmad
authors.affiliation: Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Hadi
authors.initials: H
authors.lastname: Abou-El-Hassan
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
authors.forename: Shiyue
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Dong
authors.affiliation: ER045-Laboratory of Stem Cells, DSST, Lebanese University, Beirut, Lebanon.|Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon.
authors.forename: Eva
authors.initials: E
authors.lastname: Hamade
authors.affiliation: ER045-Laboratory of Stem Cells, DSST, Lebanese University, Beirut, Lebanon.|Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon.
authors.forename: Khalil
authors.initials: K
authors.lastname: Mallah
authors.affiliation: Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Abir
authors.initials: A
authors.lastname: Zebian
authors.affiliation: Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Naify
authors.initials: N
authors.lastname: Ramadan
authors.affiliation: Department of Neurosciences, University of Messina, Messina, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.affiliation: Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Jawad
authors.initials: J
authors.lastname: Fares
authors.affiliation: Department of Surgery, Division of Neurosurgery, Lebanese American University, Beirut, Lebanon.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Comair
authors.affiliation: Department of Neurology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Samir
authors.initials: S
authors.lastname: Atweh
authors.affiliation: Faculty of Medicine-School of Nursing, American University of Beirut, New York, NY, USA.
authors.forename: Hala
authors.initials: H
authors.lastname: Darwish
authors.affiliation: ER045-Laboratory of Stem Cells, DSST, Lebanese University, Beirut, Lebanon.|Department of Biology, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon.
authors.forename: Kazem
authors.initials: K
authors.lastname: Zibara
authors.affiliation: Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX, USA.
authors.forename: Yehia
authors.initials: Y
authors.lastname: Mechref
authors.affiliation: Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
authors.forename: Firas
authors.initials: F
authors.lastname: Kobeissy
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology* / Q000627:therapeutic use; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism; D002525:Cerebellar Cortex / Q000473:pathology; D000077144:Clopidogrel; D005786:Gene Expression Regulation; D054794:Glycomics / Q000379:methods*; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: Aspirin; Clopidogrel; Neuroproteomics; PTMs; TBI