Precision Medicine for Blood Glutamate Grabbing in Ischemic Stroke

Author:

Hervella Pablo1ORCID,Sampedro-Viana Ana1ORCID,Fernández-Rodicio Sabela1,Rodríguez-Yáñez Manuel2ORCID,López-Dequidt Iria3,Pumar José M.14ORCID,Mosqueira Antonio J.14ORCID,Bazarra-Barreiros Marcos1ORCID,Abengoza-Bello María Teresa1,Ortega-Espina Sara1,Ouro Alberto56ORCID,Pérez-Mato María7,Campos Francisco7ORCID,Sobrino Tomás56ORCID,Castillo José1,Alonso-Alonso Maria Luz1ORCID,Iglesias-Rey Ramón1ORCID

Affiliation:

1. Neuroimaging and Biotechnology Laboratory (NOBEL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain

2. Stroke Unit, Department of Neurology, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain

3. Department of Neurology, Hospital Clínico Universitario de Ferrol, 15405 Ferrol, Spain

4. Department of Neuroradiology, Hospital Clínico Universitario, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain

5. NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain

6. Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain

7. Translational Stroke Laboratory (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain

Abstract

Glutamate grabbers, such as glutamate oxaloacetate transaminase (GOT), have been proposed to prevent excitotoxicity secondary to high glutamate levels in stroke patients. However, the efficacy of blood glutamate grabbing by GOT could be dependent on the extent and severity of the disruption of the blood–brain barrier (BBB). Our purpose was to analyze the relationship between GOT and glutamate concentration with the patient’s functional status differentially according to BBB serum markers (soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and leukoaraiosis based on neuroimaging). This retrospective observational study includes 906 ischemic stroke patients. We studied the presence of leukoaraiosis and the serum levels of glutamate, GOT, and sTWEAK in blood samples. Functional outcome was assessed using the modified Rankin Scale (mRS) at 3 months. A significant negative correlation between GOT and glutamate levels at admission was shown in those patients with sTWEAK levels > 2900 pg/mL (Pearson’s correlation coefficient: −0.249; p < 0.0001). This correlation was also observed in patients with and without leukoaraiosis (Pearson’s correlation coefficients: −0.299; p < 0.001 vs. −0.116; p = 0.024). The logistic regression model confirmed the association of higher levels of GOT with lower odds of poor outcome at 3 months when sTWEAK levels were >2900 pg/mL (OR: 0.41; CI 95%: 0.28–0.68; p < 0.0001) or with leukoaraiosis (OR: 0.75; CI 95%: 0.69–0.82; p < 0.0001). GOT levels are associated with glutamate levels and functional outcomes at 3 months, but only in those patients with leukoaraiosis and elevated sTWEAK levels. Consequently, therapies targeting glutamate grabbing might be more effective in patients with BBB dysfunction.

Publisher

MDPI AG

Reference66 articles.

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