Neurologic Deficit Score at 4–5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest
Cardiac arrest (CA) survivors often develop long-term neurological deficits, but its long-term impact on vulnerable brain regions and neurological outcomes remains unclear. In a previous CA model with conventional cardiopulmonary resuscitation, we found reduced heme oxygenase (HO) activity in the hi...
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MDPI AG
2025-05-01
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| Online Access: | https://www.mdpi.com/2218-273X/15/5/732 |
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| author | Wolfgang Weihs Alexandra-Maria Stommel Andrea Müllebner Alexander Franz Szinovatz Matthias Müller Ingrid Magnet Michael Holzer Andrey V. Kozlov Sandra Högler J. Catharina Duvigneau |
| author_facet | Wolfgang Weihs Alexandra-Maria Stommel Andrea Müllebner Alexander Franz Szinovatz Matthias Müller Ingrid Magnet Michael Holzer Andrey V. Kozlov Sandra Högler J. Catharina Duvigneau |
| author_sort | Wolfgang Weihs |
| collection | DOAJ |
| description | Cardiac arrest (CA) survivors often develop long-term neurological deficits, but its long-term impact on vulnerable brain regions and neurological outcomes remains unclear. In a previous CA model with conventional cardiopulmonary resuscitation, we found reduced heme oxygenase (HO) activity in the hippocampus and cortex 14 days post-CA, suggesting its potential as a functional outcome marker. Here, we used a rat model with 6 or 8 min of CA followed by extracorporeal cardiopulmonary resuscitation. While in the 6 min-CA group, 67% survived to day 14, increased mortality within 4 days resulted in only 33% survival in the 8 min group post-ROSC. All animals displayed neurological impairment assessed by daily neurologic deficit scoring (NDS). While deficits declined within the first 3–4 days in the 6 min-CA animals, the 8 min-CA group showed significantly worse neurological outcomes until day 14. Two weeks post-CA, neuroinflammatory and neurodegenerative markers (HO-1, TNF-R1, Iba1, and GFAP) were elevated in the hippocampus, while HO and 2-oxoglutarate dehydrogenase complex activities were reduced in all rats, indicating a decrease in anti-oxidative capacity and mitochondrial capacity for metabolizing glutamate. NDS at day 4–5 strongly correlated with the delayed CA-mediated enzymatic dysfunction determined in the hippocampus. This finding highlights this time point for identifying at-risk individuals and suggests a prolonged therapeutic intervention lasting at least until 4 days post-CA. |
| format | Article |
| id | doaj-art-8875e929c69b473b8b06dfedb3aeb02e |
| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
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| series | Biomolecules |
| spelling | doaj-art-8875e929c69b473b8b06dfedb3aeb02e2025-08-20T02:33:38ZengMDPI AGBiomolecules2218-273X2025-05-0115573210.3390/biom15050732Neurologic Deficit Score at 4–5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac ArrestWolfgang Weihs0Alexandra-Maria Stommel1Andrea Müllebner2Alexander Franz Szinovatz3Matthias Müller4Ingrid Magnet5Michael Holzer6Andrey V. Kozlov7Sandra Högler8J. Catharina Duvigneau9Department of Emergency Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Emergency Medicine, Medical University of Vienna, 1090 Vienna, AustriaBiological Sciences and Pathobiology, University of Veterinary Medicine Vienna, 1221 Vienna, AustriaDepartment of Emergency Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Emergency Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Emergency Medicine, Medical University of Vienna, 1090 Vienna, AustriaDepartment of Emergency Medicine, Medical University of Vienna, 1090 Vienna, AustriaLudwig Boltzmann Institute for Traumatology, Research Center in Cooperation with AUVA, Austrian Cluster for Tissue Regeneration, 1200 Vienna, AustriaBiological Sciences and Pathobiology, University of Veterinary Medicine Vienna, 1221 Vienna, AustriaBiological Sciences and Pathobiology, University of Veterinary Medicine Vienna, 1221 Vienna, AustriaCardiac arrest (CA) survivors often develop long-term neurological deficits, but its long-term impact on vulnerable brain regions and neurological outcomes remains unclear. In a previous CA model with conventional cardiopulmonary resuscitation, we found reduced heme oxygenase (HO) activity in the hippocampus and cortex 14 days post-CA, suggesting its potential as a functional outcome marker. Here, we used a rat model with 6 or 8 min of CA followed by extracorporeal cardiopulmonary resuscitation. While in the 6 min-CA group, 67% survived to day 14, increased mortality within 4 days resulted in only 33% survival in the 8 min group post-ROSC. All animals displayed neurological impairment assessed by daily neurologic deficit scoring (NDS). While deficits declined within the first 3–4 days in the 6 min-CA animals, the 8 min-CA group showed significantly worse neurological outcomes until day 14. Two weeks post-CA, neuroinflammatory and neurodegenerative markers (HO-1, TNF-R1, Iba1, and GFAP) were elevated in the hippocampus, while HO and 2-oxoglutarate dehydrogenase complex activities were reduced in all rats, indicating a decrease in anti-oxidative capacity and mitochondrial capacity for metabolizing glutamate. NDS at day 4–5 strongly correlated with the delayed CA-mediated enzymatic dysfunction determined in the hippocampus. This finding highlights this time point for identifying at-risk individuals and suggests a prolonged therapeutic intervention lasting at least until 4 days post-CA.https://www.mdpi.com/2218-273X/15/5/732rat modelventricular fibrillation cardiac arresthippocampuscortexneurodegenerationheme oxygenase |
| spellingShingle | Wolfgang Weihs Alexandra-Maria Stommel Andrea Müllebner Alexander Franz Szinovatz Matthias Müller Ingrid Magnet Michael Holzer Andrey V. Kozlov Sandra Högler J. Catharina Duvigneau Neurologic Deficit Score at 4–5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest Biomolecules rat model ventricular fibrillation cardiac arrest hippocampus cortex neurodegeneration heme oxygenase |
| title | Neurologic Deficit Score at 4–5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest |
| title_full | Neurologic Deficit Score at 4–5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest |
| title_fullStr | Neurologic Deficit Score at 4–5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest |
| title_full_unstemmed | Neurologic Deficit Score at 4–5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest |
| title_short | Neurologic Deficit Score at 4–5 Days Post-eCPR Predicts Long-Term Brain Dysfunction in Rats Following Cardiac Arrest |
| title_sort | neurologic deficit score at 4 5 days post ecpr predicts long term brain dysfunction in rats following cardiac arrest |
| topic | rat model ventricular fibrillation cardiac arrest hippocampus cortex neurodegeneration heme oxygenase |
| url | https://www.mdpi.com/2218-273X/15/5/732 |
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