Hyperthermia and Early Growth of Cerebral Infarct: The Potential Role of Blood–Brain Barrier Permeability

Hyperthermia within the first 24 h following ischemic stroke (IS) has been associated with poor outcomes. We sought to determine whether blood-brain barrier (BBB) permeability contributes to the relationship between hyperthermia and early infarct growth (EIG). A retrospective analysis was conducted on a prospective stroke biobank. EIG was defined as the percentage difference between the initial volume (mL) determined by the diffusion-weighted imaging at admission and the volume (mL) from the control CT image on the 4 th-7 th day. Hyperthermia was defined as an axillary body temperature ≥ 37.5 °C within the first 24 h. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) serum levels were measured by ELISA. One-hundred and two (19.7%) patients showed EIG from a cohort of 519 patients (45.6% females). Linear correlation was observed for axillar body temperature and EIG (Pearson's r = 0.46; p < 0.001). sTWEAK serum levels showed a c-statistic of 0.74 (95% CI: 0.69-0.79), with an optimal cut-off point > 3000 pg/mL for EIG prediction. Moreover, microalbuminuria levels strongly correlated with sTWEAK levels (Pearson's r = 0.75; p < 0.001). In the multivariate analysis for EIG was observed an independent association with hyperthermia (adjusted OR 24.21; 95% CI: 12.03-39.12), sTWEAK levels > 3000 pg/mL (adjusted OR 16.43; 95% CI: 3.71-72.70), leukoaraiosis (adjusted OR 10.42; 95% CI: 2.68-39.08), and microalbuminuria (adjusted OR 1.02; 95% CI: 1.00-1.12). In our cohort, hyperthermia was independently associated with EIG after IS. The fact that microalbuminuria, leukoaraiosis, and sTWEAK were also associated with EIG suggests a relationship with increased BBB permeability.

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Journal
Translational Stroke Research
Published
2025-04-07
DOI
https://doi.org/10.1007/s12975-025-01349-x
Primary Topic
Intracerebral and Subarachnoid Hemorrhage Research
Type
article
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article

Hyperthermia and Early Growth of Cerebral Infarct: The Potential Role of Blood–Brain Barrier Permeability

Sabela Fernández‐Rodicio, Antonio J. Mosqueira, Manuel Rodríguez‐Yáñez, Arturo González‐Quintela et al.
Translational Stroke Research
Intracerebral and Subarachnoid Hemorrhage Research
article

Hyperthermia and Early Growth of Cerebral Infarct: The Potential Role of Blood–Brain Barrier Permeability

Sabela Fernández‐Rodicio, Antonio J. Mosqueira, Manuel Rodríguez‐Yáñez, Arturo González‐Quintela, Jacobo Porto-Álvarez, Pablo Hervella, Tomás Sobrino, Marcos Bazarra‐Barreiros, Crhistian‐Mario Oblitas, Ramón Iglesias‐Rey, María Luz Alonso-Alonso, Francisco Campos Freire, Iria López‐Dequidt, José Castillo, Alberto Ouro, Ana Sampedro‐Viana, Sara Ortega-Espina, María Teresa Abengoza-Bello, Javier Martínez Fernández
article en

Abstract

Hyperthermia within the first 24 h following ischemic stroke (IS) has been associated with poor outcomes. We sought to determine whether blood-brain barrier (BBB) permeability contributes to the relationship between hyperthermia and early infarct growth (EIG). A retrospective analysis was conducted on a prospective stroke biobank. EIG was defined as the percentage difference between the initial volume (mL) determined by the diffusion-weighted imaging at admission and the volume (mL) from the control CT image on the 4 th-7 th day. Hyperthermia was defined as an axillary body temperature ≥ 37.5 °C within the first 24 h. Soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) serum levels were measured by ELISA. One-hundred and two (19.7%) patients showed EIG from a cohort of 519 patients (45.6% females). Linear correlation was observed for axillar body temperature and EIG (Pearson's r = 0.46; p < 0.001). sTWEAK serum levels showed a c-statistic of 0.74 (95% CI: 0.69-0.79), with an optimal cut-off point > 3000 pg/mL for EIG prediction. Moreover, microalbuminuria levels strongly correlated with sTWEAK levels (Pearson's r = 0.75; p < 0.001). In the multivariate analysis for EIG was observed an independent association with hyperthermia (adjusted OR 24.21; 95% CI: 12.03-39.12), sTWEAK levels > 3000 pg/mL (adjusted OR 16.43; 95% CI: 3.71-72.70), leukoaraiosis (adjusted OR 10.42; 95% CI: 2.68-39.08), and microalbuminuria (adjusted OR 1.02; 95% CI: 1.00-1.12). In our cohort, hyperthermia was independently associated with EIG after IS. The fact that microalbuminuria, leukoaraiosis, and sTWEAK were also associated with EIG suggests a relationship with increased BBB permeability.

Translational Stroke ResearchVol. 16(5)
Universidade de Santiago de Compostela (ES), Instituto de Salud Carlos III (ES), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Complejo Hospitalario Universitario de Santiago (ES), Centro de Investigación Biomédica en Red (ES), Complexo Hospitalario Universitario A Coruña (ES), Instituto de Investigación Sanitaria de Santiago (ES), Instituto de Investigación de Enfermedades Raras (ES), Complejo Hospitalario Universitario de Ferrol (ES)
Ministerio de Ciencia e Innovación, Xunta de Galicia, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, European Regional Development Fund
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Openalex Percentile: Top 88%
Intracerebral and Subarachnoid Hemorrhage Research
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