Biomedical subjects

Gokhan Yilmaz

Publications and source records attributed to Gokhan Yilmaz.

4 recordsLinked to original sources

PubMed2025

Emerging biomarkers in ischemic stroke.

Ischemic stroke is a devastating global public health problem and the leading cause of acute death and chronic disability. Despite being the diagnostic cornerstone, limitations in neuroimaging, including availability, cost, and therapeutic window, have rekindled interest in biomarker-based approaches. Biomarkers will be employed to facilitate the eventual prediction, early diagnosis, and prognosis of strokes, as well as to inform person-centered medicine. This review summarizes recent advances in the search for biomarkers related to inflammatory, endothelial, metabolic, and neuroaxonal pathways. Interleukin-6 (IL-6), asymmetric dimethylarginine (ADMA), endothelial microparticles (EMP), and homocysteine serve as predictive biomarkers corresponding to vascular risk and inflammatory priming. Glial fibrillary acidic protein (GFAP), D-dimer, and neuron-specific enolase (NSE) are diagnostic markers that can already subtype stroke and estimate lesion burden. Prognostic biomarkers, such as serum neurofilament light chain (sNfL), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), and growth differentiation factor 15 (GDF-15), are associated with infarct size and long-term outcomes. The -omic sciences (genomic, proteomic, and metabolomic) have discovered defined molecular signatures and panels with high specificity to describe heterogeneity in stroke. Cerebrospinal fluid (CSF) biomarkers and newer imaging modalities, such as those provided through positron emission tomography/computed tomography (PET/CT), offer valuable adjuncts to blood biomarkers in the diagnosis of conditions. Translational potential is hindered by heterogeneity in the transcriptional landscape.

Ischemic stroke↗

PubMed2006

Gamma secretase-mediated Notch signaling worsens brain damage and functional outcome in ischemic stroke.

Mice transgenic for antisense Notch and normal mice treated with inhibitors of the Notch-activating enzyme gamma-secretase showed reduced damage to brain cells and improved functional outcome in a model of focal ischemic stroke. Notch endangers neurons by modulating pathways that increase their vulnerability to apoptosis, and by activating microglial cells and stimulating the infiltration of proinflammatory leukocytes. These findings suggest that Notch signaling may be a therapeutic target for treatment of stroke and related neurodegenerative conditions.

Amyloid Precursor Protein Secretases↗

PubMed2006

Role of T lymphocytes and interferon-gamma in ischemic stroke.

BACKGROUND: Although lymphocyte recruitment and activation are associated with cerebral ischemia-reperfusion (I/R) injury, the contributions of specific lymphocyte subpopulations and lymphocyte-derived interferon-gamma (IFN-gamma) to stroke remain unknown. The objectives of this study were to define the contribution of specific populations of lymphocytes to the inflammatory and prothrombogenic responses elicited in the cerebral microvasculature by I/R and to investigate the role of T-cell-associated IFN-gamma in the pathogenesis of ischemic stroke. METHODS AND RESULTS: Middle cerebral artery occlusion was induced for 1 hour (followed by 4 or 24 hours of reperfusion) in wild-type mice and mice deficient in lymphocytes (Rag1(-/-)), CD4+ T cells, CD8+ T cells, B cells, or IFN-gamma. Platelet and leukocyte adhesion was assessed in cortical venules with intravital video microscopy. Neurological deficit and infarct volume were determined 24 hours after reperfusion. Rag1(-/-), CD4+ T-cell(-/-), CD8+ T-cell(-/-), and IFN-gamma(-/-) mice exhibited comparable significant reductions in I/R-induced leukocyte and platelet adhesion compared with wild-type mice exposed to I/R. Infarct volume was reduced and I/R-induced neurological deficit was improved in immunodeficient Rag1(-/-) mice. These protective responses were reversed in Rag1(-/-) mice reconstituted with either wild-type or, to a lesser extent, IFN-gamma(-/-) splenocytes. B-cell-deficient mice failed to show improvement against ischemic stroke injury. CONCLUSIONS: These findings indicate that CD4+ and CD8+ T lymphocytes, but not B lymphocytes, contribute to the inflammatory and thrombogenic responses, brain injury, and neurological deficit associated with experimental stroke. Although IFN-gamma plays a pivotal role in stroke-induced inflammatory responses, T lymphocytes appear to be a minor source of this cytokine.

Animals↗

PubMed2005

CD40/CD40 ligand signaling in mouse cerebral microvasculature after focal ischemia/reperfusion.

BACKGROUND: CD40/CD40 ligand (CD40L) signaling contributes to proinflammatory and prothrombogenic responses in the vasculature. CD40/CD40L expression is elevated in patients after a transient ischemic attack or stroke. The purpose of this study was to investigate the role of CD40/CD40L signaling in cerebral microvascular dysfunction and tissue injury response to middle cerebral artery occlusion (MCAO) and reperfusion. METHODS AND RESULTS: Intravital fluorescence microscopy was used to visualize the cerebral microcirculation of wild-type (WT), CD40-deficient, and CD40L-deficient mice subjected to 1-hour MCAO and 4-hour reperfusion. The adhesion of platelets and of leukocytes and vascular permeability were measured in postcapillary venules after 4-hour and 1-hour reperfusions, respectively. Cerebral infarct volume was analyzed 24 hours after reperfusion. Platelet and leukocyte adhesion was elevated and blood/brain barrier function was compromised by MCAO in WT mice. Blood cell recruitment and increased permeability were blunted in both CD40-deficient and CD40L-deficient mice. Infarct volume was also reduced in CD40- and CD40L-deficient mice compared with WT mice. CONCLUSIONS: Our findings indicate that CD40/CD40L signaling contributes to inflammatory and prothrombogenic responses and brain infarction induced by MCAO and reperfusion. The CD40/CD40L dyad may play a significant pathogenic role in the acute phase of ischemic stroke.

Animals↗